Continental J. Pharmaceutical Sciences Volume 4 (2010)

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Pharmaceutical Sciences 4: 1 - 5, 2010                                                               ISSN: 2141 - 4149

© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

PRELIMINARY PHYTOCHEMICAL SCREENING, ANTIBACTERIAL ACTIVITY AND ELEMENTAL ANALYSIS OF THE LEAVES AND THE ROOT BARK OF Parinari curatellifolia Planch Ex Benth (Chrysobalanaceae).



Halilu, M.E1, Yebpella, G.G2, Hassan, L.G3 and Achor.M 4

1*Department of Pharmacognosy and Ethnomedicine, Usmanu Danfodiyo University, Sokoto-Nigeria.

2National Research Institute for Chemical Technology(NARICT) Zaria-Nigeria.

3Department of Pure and Applied Chemistry, Usmanu Danfodiyo University, Sokoto-Nigeria.

4Department of Pharmaceutics and Pharmaceutical Microbiology, Usmanu Danfodiyo University, Sokoto-Nigeria.



ABSTRACT: Parinari curatellifolia has various uses in Ethnomedicine. It is used in the treatment of cancer, pneumonia, fever, microbial infections, anti-inflammation, dressing of fracture and dislocation. The Phytochemical screening of the ethanolic extracts of the leaves and the root bark revealed the presence of terpenoids, saponins, flavonoids, cardiac glycosides, and tannins. Alkaloids were found to be present in leaves only, while anthraquinones were found to be present only in the root bark. The elemental analysis indicated the presence of the following mineral elements in both the leaves and the root bark  in various concentrations: k, Na, Ca, Al, Cu, Ni, Zn, Mn, Co, Cr, Pb and Cd. The plant is reported to have been used in the treatment of various diseases. This may be due to the presence of the Phytochemicals being detected.



KEYWORDS: Phytochemical Screening, Elemental Analysis, Parinari curatellifolia, Antibacterial activity and Phytochemicals



INTRODUCTION

The history of the use of herbs dates back to the time of the early man. The early man used herbs to keep fit (Kafaru, 1994). Different medicinal plants have different medicinal properties. No one herb is found to be used for just one purpose (Kafaru, 1994). Parinari curatellifolia belongs to the family of plants chrysobalanaceae. It is used traditionally, in the treatment of cancer, pneumonia, fever, microbial infections, anti-inflammation, dressing of fracture and dislocation. The acute toxicity in mice and subchronic toxicity of the hydroethanolic extract of the seeds of P. curatellifolia was evaluated. The study showed LD50 of 7.27 g/kg body weight (Steve et al., 2009). The antibacterial properties of the aqueous, Ethylacetate, n-butanol and methanolic extracts of the stem bark of P. curatellifolia have been evaluated on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The extracts, inhibited the growth growth of the microorganisms with the minimum zones of inhibitions ranging from 12-34 mm (Halilu et al., 2008). The chemomicroscopic evaluation of the stem bark of P. Curatellifolia revealed the presence of cellulose, lignin, mucilage, starch, oils and proteins. The microscopic evaluation also revealed the presence of fibres, phloem, starch grains, calcium oxalate crystals, cork cells and sclereids (Halilu, et al., 2008)2. Apart from the pharmacological effect of P. Curatellifolia, it could turn out to be toxic due to the presence of heavy elements and other impurities that might have been accumulated in the plant over the years. The accumulation of the elements and the impurities might be due to environmental pollution (Ajasa et al., 2004). Therefore, this research is design to evaluate the antibacterial activity (root bark), phytochemical constituents and to determine the levels (concentrations) of some elements in the  leaves and the root bark of the plant.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Collection of Plant Material.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The leaves and the root bark of the plant were collected in June 2009 in Jaji-Kaduna State, Nigeria. The plant has been previously identified and authenticated at the Herbarium Unit of the department of Biological Sciences, Ahmadu Bello University, Zaria, Nigeria. The voucher with Specimen number 903 is deposited at the Herbarium unit for reference.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Preparation of Plant Material.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The leaves and the root bark of the plant were cleansed thoroughly in other to free it from dust, soils and other unwanted materials that may adhere to it. The Plant sample were air dried and then ground to fine powder using pestle and mortar and then stored in an appropriate container until required for use.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Halilu, M.E et al: Continental J. Pharmaceutical Sciences 4: 1 - 5, 2010.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Extraction of Plant Material.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">150 g of the powdered leaves and root bark were extracted with 500 ml of ethanol using maceration method. Each of the samples were filtered and then evaporated to dryness using a rotator evaporator. The resulting extracts were then used for the Phytochemical screening and antibacterial.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Phytochemical Screening.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The leaves and the root bark were screened for the presence of the various Phytochemicals using the methods of: Brain and Turner (1975); Evans (2005) and Harbone (1973).

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Antibacterial Activity

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The test organisms used were standard strains of Bacillus subtilis (NCTC 10342), Staphylococcus aureus (CATCC 13969), Escherichia coli (NCTC 10418) and Pseudomonas aeruginosa (ATCC 1853). The microorganisms were obtained from the Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria. The bacterial species were grown for 24 h in nutrient broth and diluted to 1:5000 for gram negative bacteria and 1:1000 for gram positive bacteria.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Susceptibility Test

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">20 g of Muller Hilton agar was mixed with distilled water and then sterilized in an autoclave for 15 minutes. The sterilized media was poured into petri dishes. The solidified plates were flooded with the various dilutions of the test bacteria and drained with sterile Pasteur piprtte. Wells measuring 8.0 mm in diameter were bored into the inoculated plates using cork borer (No.4). The wells were filled with the ethanolic extracts (50 mg/ml) and ampicllin (0.01 mg/ml) was used as the negative control.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Mineralization of Samples.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">For the conversion of solid to liquid, a wet digestion technique was used. 0.5 g of the fine powdered samples were placed in beakers for digestion. The contents of the beakers were treated with a mixture of HNO3 and H2O2 in the ratio of 1:1. The beakers with their contents were placed on hot plates in a fume cupboard and heated electrically to boil until all the brown fumes of NO2 disappeared, leaving behind a colourless liquid. After mineralization, samples were transferred quantitatively to 50 mls volumetric flask and made to mark with de-ionized distil water.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Elemental Analysis.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The aliquots of the digested samples were analysed for metals of interest using Atomic Absorption Spectrophotometer (AAS). Qualitative analysis of the samples were achieved by interpolating the relevant calibration curves prepared from standard metal solution of the aqueous standards.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Statistical Analysis.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The results of the elemental analysis were expressed as mean ± standard error. The Paired sample test using SPSS version 10 was used for the evaluation of data and p˂0.05 accepted as significant.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Phytochemical screening of the leaves and the root bark, revealed the presence of terpenoids, saponins, flavonoids, cardiac glycosides and tannins. Alkaloids were found to be present only in leaves, while anthraquinones were found to be present only in the root bark. Cyanogenetic glycosides were found to be absent in both the leaves and the root bark (Table 1). At 50 mg/ml concentration, the ethanolic extract produced zone diameter of 14-28 mm against the test bacteria. Ampicillin at 0.01 mg/ml concentration produced inhibition zones ranging from 14-34 mm against the test bacteria (Table 2). The activity of the extract was higher on the gram positive bacteria than the gram negative bacteria (see table 2). The significant difference in their susceptibilities to the extract might be related to the structural differences in the cell envelope compositions of the gram negative and the gram positive bacteria. The gram positive cell envelope is simple while that of gram negative is complex consisting of lipoproteins outer membrane and lipopolysaccharides (Jawetze et al., 1978). The outer membrane of the gram negative cell outer envelope does block the penetration of large molecules and hence the relative resistance of gram negative bacteria to some antibacterial agents (Jawetze et al., 1978). The elemental analysis show higher concentrations of macro elements such as K(3277.51±93.72 µg/g) in the leaves and 4403.23±695.18 µg/g in the root bark, Na(42576.22±3470.01 µg/g) in the leaves and 4447.24±6086.65 µg/g in the root bark, Ca(7039.80±105.04 µg/g) in the leaves and 12585.29±190.96 µg/g in the root bark. Some trace elements were also detected in a large amount. Zn(97.07±8.42 µg/g) in the leaves and 66.62±8.49 µg/g in the

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Halilu, M.E et al: Continental J. Pharmaceutical Sciences 4: 1 - 5, 2010.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">root bark, Cu(2.60±0.37 µg/g) in the leaves and 8.59±2.26 µg/g in the root bark, Ni(26.53±6.81 µg/g) in the leaves and 24.14±0.32 µg/g in the root bark, Mn(19.85±1.08 µg/g) in the leaves and 14.55±0.34 µg/g in the root bark, Co(28.69±0.10 µg/g) in the leaves and 9.070±2.79 µg/g in the root bark, Cr(29.33±11.01 µg/g) in the leaves and 44.53±11.72 µg/g in the root bark. Some heavy elements were also detected in lower concentrations: Cd(6.93±0.84 µg/g) in the leaves and 5.86±0.56 µg/g in the root bark while the concentration of Pb was found to be (15.68±1.49 µg/g) in the leaves and 17.76±0.33 µg/g in the root bark. Al was also detected with a concentration of 58.72±1.59 µg/g in the leaves and 63.04±4.69 µg/g in the root bark (Table 3). The concentrations of Cd, Pb, Cu, Ni, Al, Na and K that were detected in the leaves, when compared with the ones detected in the root bark at p˂0.05, were not significant. On the other hand, the concentrations of Zn, Mn, Co, Cr, and Ca that were detected in the leaves, when compared with the ones detected in the root bark at p˂0.05 were significant. The elemental analysis has shown high concentration of Ca, Na and K (Table 3). These elements are very necessary in human nutrition. Ca is very important in the development of strong bones and teeth. K and Na are required to repair worn out tissues and building of red blood cells (WHO, 1996). Trace elements such as: Zn, Cu, Co and Mn were also present in a large concentrations (Table 3). These elements are required by plants in small quantities by plants for their normal growth. Mn and Zn are also essential in enzyme metabolism. The various concentrations of these elements in plants is very important. Mn is an important modulator of cell functions and plays an important role in the control of diabetes mellitus (Korc, 1998). Heavy elements like: Pb and Cd were also detected in a lower concentrations (Table 3). These concentrations are low when compared with the acceptable daily intake of 10 mg/kg (WHO, 1996). Although these concentrations are low, Pb and Cd are known to be toxic even at lower concentrations.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Table 1:Phytochemical Constituents of the leaves and the root bark of Parinari curatellifolia. <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Alkaloids                                                                             +                                                              _

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Anthraquinones                                                                  _                                                              +

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Tannins                                                                                +                                                              +

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Terpenoids                                                                           +                                                              +

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Cyanogenetic glycosides                                                   _                                                              _

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Flavonoids                                                                           +                                                              +

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Saponins                                                                              +                                                              +

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Cardiac glycosides                                                             +                                                              + <p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">

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<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">Table 2: Antibacterial activities of ethanolic extract of the root bark of P. Curatellifolia. <p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">                                    Ethanolic Extract               Ampicillin (0.01 mg/ml) <p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">B. subtilis                       28.00±1.15                                  34.00±3.21

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;"> S. aureus                        20.00± 0.57                                22. 00±2.51

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;"> P. aeruginosa                14.00±1.00                                  14. 00±0.57

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;"> E. coli                            18.00±1.54                                  17.00±1.73 <p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Halilu, M.E et al: Continental J. Pharmaceutical Sciences 4: 1 - 5, 2010.

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 42.55pt; text-align: justify; text-indent: -42.55pt; line-height: normal;">Table 3: Various concentrations of the elemental constituents of the leaves and the root bark of P. curatellifolia expressed in µg/g. <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">We have shown that the ethanolic extract of the root bark of P. Curatellifolia had antibacterial activity. The results of the Phytochemical screening and antibacterial studies has to some extent validate the ethnomedical application of the plant in treatment of microbial infections. This may be due to presence of the secondary metabolites that were detected. The elemental analysis had shown that the plant has accumulated some toxic elements (Pb and Cd).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">REFERENCES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ajasa, A.O., Bello, M.O., Ibrahim, O.A., Ogunwande, I.A and Olawore, N.O. (2004). Heavy trace metal and macro nutrients status in herbal plants of Nigeria. Food Chem., 85:67-71.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Aliyu, A.B., Musa, A.M., Oshanimi, J.A., Ibrahim, H.A and Oyewale, A.O. (2008). Phytochemical analyses and mineral element composition of some medicinal plants of northern Nigeria. ''Nig. journal of pharm sci''. Vol.7(1), March 2008. Pp 119-125.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Brain, K.R and Turner T.D. (1975). The practical Evaluation of Phytopharmaceuticals. Wright-scientechnica, Pp 90-121.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Cowan, M.M. (1999). Plant products as antimicrobial agents: Clinical microbiology review. Vol. 12 Pp560-585.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Evans, W.C.(2005). Trease and Evans Pharmacognosy. 15th Edition. Elsevier India. Pp135-150.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Edeoga, H.O. and Eriata, D.O. (2001). Alkaloids, Tannins, Saponin contents of some Nigerian medicinal plants. ''Journal of med. Aromatic Plant Sci'' 23:344-349.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Halilu, M.E., Akpulu, I.K., Agunu, A., Ahmed, A and Abduraman, E.M. (2008).Phytochemical and antibacterial Evaluation of the stem bark of Parinari curatellifolia Planch ex Benth (Chrysobalanaceae). Nigerian journal of Basic and Applied Sciences Vol.16(2). Pp272-276.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Halilu, M.E., Agunu, A., Ibrahim, H and Abduraman, E.M. (2008). Pharmacognostic Evaluation of the Stem bark of  Parinari curatellifolia Planch ex Benth (Chrysobalanaceae). Nigerian journal of Pharmaceutical Sciences Vol.7(1). Pp79-85.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Harbone, J.B. (1973). Phytochemical Methods: A guide to modern techniques of plant analysis. Chapman and Hall Ltd. London. Pp49-188.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">John, J.L. (2000). Antimicrobial Properties of Tannins: www.geocites.com/johnjlal/tannin

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Halilu, M.E et al: Continental J. Pharmaceutical Sciences 4: 1 - 5, 2010.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Kafaru, E. (1994) immense help from nature’s work shop, guidelines on How to use herbs to achieve healthy living. Elikf Health Services. Pp 6-10.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Kraft, c., Jenett-Siems, K., Jakupovic, J., Mavi, s., Bienzle, U and Elich, E. (2003). Invitro antiplasmodial Evaluation of Medicinal Plants from Zimbabwe. Phytotherapy Resaerch 17(2):123-128.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Korc, M. (1998). Manganese homeostasis in human and its role in disease states. In:Prasad, A.s.(ed). Essential and Toxic trace Elements in human Health and Disease. Alan R. Liss Inc. New York. Pp253-264.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Natalie, T.R., Xu, l., Raymond, J.A. and Michel, R. (2001). G2 DNA Damage checkpoint inhibition and antimitotic activity of 13-hydroxy-15-oxozoaptlin. ''Biol. Chem''.27(51):48231-48236

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Steve, O.O., Sunday, O.O., Emmanuel, N.A., Veronica, N.E and Olawale, O.P (2009). Evaluation of acute toxicity in mice and subchronic toxicity of hydroethanolic extract of P. Curatellifolia Planch (chrysobalanaceae) seeds in rats. African Journal of Biotechnology, Vol 8 (9), Pp1800-1806.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">WHO (1996). Trace Elements in Human Nutrition and Health. WHO Technical Report Series Geneva. Pp119-205.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 05/04/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 14/04/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Halilu, M.E, Department of Pharmacognosy and Ethnomedicine, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto-Nigeria.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Email: [mailto:emshelia2002@yahoo.com emshelia2002@yahoo.com]

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 6 - 9, 2010                                                               ISSN: 2141 - 4149

<p style="text-align: justify;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">FACTORS THAT MILITATE AGAINST THE USE OF NURSING PROCESS: A HOSPITAL BASED STUDY

<p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">1Momoh, M. A and 2 Chukwu,  D. O

<p style="text-align: center;">1Department of Pharmaceutics, University of Nigeria Nsukka, Enugu State, and 2School of Midwifery, Bishop Shanahan Hospital, Nsukka, Enugu State

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<p style="margin: 0cm 43.2pt 0.0001pt; line-height: normal;">ABSTRACT

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">Nursing process is a global concept which forms the foundation of the nursing profession. The use of nursing process in most hospitals is lagging behind despite all the effort of nursing professionals to implement its use. This research work examined the factors nurses perceived as constraints to its implantations in Federal Medical Center, Owerri. A self-developed questionnaire tested for validity and reliability was used to elicit responses from a randomly selected 100 nurses. Findings revealed that 41 % have knowledge of nursing process while 59 % do not. Majority 78 % responded that shortage of staff affects its use while 22 %  believed not. On negative attitude of nurses towards the use of nursing process 84 % of respondent accepted the option while 16% disagreed. Majority of the respondents 70 % accepted that there is relationship between nursing process and patient’s care while 30 % opposed to that view. Among the major constraining factor identified were: negative attitude of nurses, shortage of staff and lack of knowledge as evident from the study.

<p style="margin: 0cm 43.2pt 0.0001pt; line-height: normal;">

<p style="margin: 0cm 43.2pt 0.0001pt; line-height: normal;">KEYWORDS: Militate, nurse process, care, patients.

<p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The introduction of nursing process as a systematic and scientific approach to patient’s care started in the early 60s in the developed countries and had brought tremendous improvement to the quality of nursing care rendered to all categories (American Nurses Association (2000). Since the introduction of nursing process, it has remained a classroom topic in schools of nursing/midwifery and departments of nursing in Nigeria (Berman, (2000). In the mid 1980s, initial attempt was made on its practice in most teaching hospitals in Nigeria. The nursing and midwifery council of Nigeria also responded by organizing Nursing process workshops which culminated in the production of nursing care plan formats by the council for its use by all healthcare institutions nationally (Carpenito, (2000). These were laudable efforts but the main problem remained, as very low level of implementation of nursing process was observed in Nigerian hospitals after about ten years of trails (Craven, and Hirnle (2002).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Despite all these efforts, nurses still have problems in the use of nursing process, upon all workshop held to equipped the nurse with necessary skills, they seemed to have minimal impact in the use of nursing process in the care of their patients. All these efforts have proved abortive especially among nurses in this part of the world. Most of the problems identified militating against its use includes: poor knowledge of nursing process by most nurses to write care plan, time factors: This means that nursing process is time consuming, failure of nurses leaders to motivate the use of nursing process, negative attitude of nurses/midwives towards the use of nursing care plan/process and shortage using staff.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Nwonu (2002) found that nurses perceived the nursing process as a “professional code of practice” which may be counter-productive for those nurses who do not wish to assume accountability from independent decision-making in the patient’s care.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESEARCH DESIGN

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Descriptive method was used for this study because it is concerned with the collection of data for the purpose of designing and interpreting existing condition, prevailing practices and on going process.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Area of Study

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This research was carried out in Federal Medical Center, Owerri, Imo State. The hospital consist of II wards, namely; accident and Emergency (ward I), male orthopaedic (ward 2), safe vaginal delivery ward (ward 3), obstetrics and gynaecological ward (ward 4), labour ward (ward 5), medical paediatric ward (ward 6), female surgical ward (ward II) to mention but a few.

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Momoh, M. A and Chukwu,  D. O: Continental J. Pharmaceutical Sciences 4: 6 - 10, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Population of the Study

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The study was made of 100 randomly selected nurses without discrimination in their professional status out of 438 nurses working at the federal medical centre Owerri. The selection of sample size, simple random technique was adopted which ensured equal chances of each person being included in the study.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Method of Data Collection

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A self developed questionnaire was used. It was made up closed ended questions. The questions were structured in English language. The questions gave respondents the chances of choosing from “yes” or “No” Options fifteen questions were generated, 100 copies were produced and distributed after full explanation of the purpose of the study to the subjects. A face to face method of filling and collection was used, after distribution 100 % of the questions were collected the same day.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Data Analysis

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The questionnaire was collected and analyzed using Statistical Package for Social (SPSS version 14) and presented in pie chart frequency table.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ethical Consideration

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The subjects of the research were made to understand the nature and purpose of the research. They gave their free and informed consent to be used for the study. The rights and concerns of the subjects were given priority and confidentiality was maintained in the course of the research.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Table 1: Do nurses have adequate knowledge of nursing process and skills to write nursing care plan?

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">From the Table 1. 41 respondents have adequate knowledge of what nursing process entails and posses the skill to write care plan while 59 respondents showed lack of knowledge and skills.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure 1 showed that 78 % of the respondents believed that shortage of staff affects the use of nursing process while 22 % respondents said it does not.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Momoh, M. A and Chukwu,  D. O: Continental J. Pharmaceutical Sciences 4: 6 - 10, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure 2 showed that 84 % of the respondents indicated that negative attitude of nurses affects the use of nursing process, while 16 %, of the respondents disagreed to that view.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">From Figure 3 it was deduced that 69 % respondents agreed that there is relationship between nursing process and patient’ care, while 31% disagreed. This simply mean that if a nurse understand their procedure well there could be a direct impact in the services the nurse render to his or her client, this translated to say that good knowledge of nurses procedure is directly proportional to their services.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Findings shows that most respondents consented that nurses have poor knowledge of nursing process and skill for writing nursing care plan as shown in (Table 1). This is in agreement with the study carried out by Nwonu, (2002) on  the factors militating against the uses of nursing process in the care of the patients among nurses, in his study he concluded that there a lot factor ranging from personnel and poor attitude of the health giver toward documentation. The result show that greater proportion of the respondents (59 %), have poor knowledge despite all workshops, seminars held by nursing professionals to improve the knowledge of nurses on nursing process and care plan and this will go a long way to affect the efficiency of nursing in their various practice. Although, few respondents (41 %) were found to have adequate knowledge, this was as a result of the series of training attended. This is further collaborated by the study carried out, where the researcher concluded that despite the issue of negligence some are still up and doing in their respective services, though below the expected number of nurses that were trained (Ojo, and Irinoye, (2004).

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Momoh, M. A and Chukwu,  D. O: Continental J. Pharmaceutical Sciences 4: 6 - 10, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In respondents to question 2 as shown in (Fig. 1) 78 %, believed that shortage of staff jeopardizes the use of nursing process. According to Nancy (2006) in his report, shortage of staff is the most factors that affect the use of nursing care plan, this is so because there are a lot of works to contend with, many nurses regardless of his or her knowledge do not have enough time to do nursing care plan. This has been proved to be one of the most serious issues that affected the services of health personnel in general, it was observed especially in the developing countries Nigeria inclusive where nurses and other health personnel carried out daily obligation without recourse to the expected number of patients to a particular personnel, nurse are worst hit in this direction, a situation where a single nurse is to be saddled with responsible of taking care more than 15 patients in the ward, this happened in both missionary and government health facilities. Meanwhile, few of them 22 % said that shortage of staff is does not affect the use of nursing process. This group must have believed that if nurses is determine to follow the ethics shortage of staff must not be an excuse especially if the nurse is fully educated on the importance of nurse process.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Fig. 2 shows the response on whether negative attitude of nurses affects the use of nursing process? A total of 84 % of the respondents were found to indicate that negative attitude of nurses affects the use of nursing process/care plan. This perceived attitude of nurses agreed with the view of other researcher on the same subject (Ejike M.O (2009). According to the study, he opined that, the nurse resistance to change with new trends in nursing practice, inability to adequately address patients and their relatives as a result of poor ineffective skill (Ariesbsn, (2005). More so, a study carried out among Ghanaian nurse portrayed negligence and poor documentation skill as negative attitude of nurses towards the use of nursing process (Lewis, (2006). Meanwhile, few respondents (16 %) disputed the above finding with reasons best known to them.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Fig. 3, show the response on whether there is any relationship between nursing process and patient’s care? A total of 70 % respondents agreed that there is a relationship between nursing process and patient’s care and 30 % disagreed. The result of the positive acceptance tally with the view of the previous research which opined that nursing process helps to individualized care, ensuring that patients receives adequate and sound care, he went further to illustrate on the issue of pain management in sickle cell cases (Nwagwu, (2003). Study by a researcher (Popoola, 2002), gave support to the previous authors, in his work he pointed out of the view that nursing process helps in proper documentation of the patients’ history through data collection and this a long way to help drug rational, contraindication in therapy as well as the uses of non-pharmacological management. This our research have elucidated the importance of nursing process and the likely obstacles that need to be overcome, we further advocate a wider scope of study in a specialized health setting so as to give backing on the need for government and health policy maker to redesigned their approach toward health personnel especially on staff strength, salary and periodic training program.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">REFERENCES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">American Nurses Association (2000). Nursing A Social policy statement, Kansas city.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Berman, A.J., (2000). Fundamentals of nursing concepts, process and practice, 6th edition, New Jersey: prentice Hall Health.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Carpenito, L.J, (2000). Nursing diagnosis. Application to clinical practice, 8th edition; Philadelphia: Lippincott.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Craven, FR and Hirnle J. C (2002). Fundamentals of nursing process: Advanced Journal of Nursing. 13(2)156-159.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Nwonu, E.E (2002). Nursing process concept and practice. Enugu Snaap Press Ltd.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ojo, A.A and Irinoye, O.O (2004). ''Nurses knowledge and attitudes towards implementation of Nursing process. West African Journal of Nursing''. 13(2): page 102 -109.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Nancy, S. R. (2006). Principles and practice of Nursing, India: N.R. Publication House.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ejike M.O (2009). The practice of Normal Midwifery. Mike social publishers, Nsukka.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ariesbsn A.A (2005). Quality Nursing education and practice: Effective tools for professionalism: West African Journal of Nursing. 16(2): page 64-69.

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Momoh, M. A and Chukwu,  D. O: Continental J. Pharmaceutical Sciences 4: 6 - 10, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Lewis, T. L (2006). Leaping the chasin between theory and practice, ''Journal of Advanced Nursing. '' 14(1), 13-21

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Nwagwu, A. S (2003). Concept and Ethics in Nursing, A Basic Text for Collage and schools of Nursing and Midwifery. Owerri Solos Group of Associates.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Popoola M.M (2002): The holistic approach to therapy for venous states leg ulcer. The American Journal of Nurse Practitioners: 7 (7), 9-18

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/04/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/04/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; line-height: normal;">Momoh, M. A

Department of Pharmaceutics, University of Nigeria Nsukka, Enugu State

<p style="text-align: justify; line-height: 200%;">Email: [mailto:jointmomoh@yahoo.com jointmomoh@yahoo.com]

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010                                           ISSN: 2141 - 4149

<p style="text-align: justify;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">SOME PHYSICAL CHARACTERISTICS OF MICROCRYSTALLINE STARCH OBTAINED FROM MAIZE AND CASSAVA

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M1, Oyi, A.R2 and Isah, A.B2.

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">1Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria and 2Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.

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<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">ABSTRACT

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">The work was aimed to investigate the suitability of microcrystalline starch (MCS) obtained from maize and cassava grown in Nigeria for use as pharmaceutical excipients. MCS was obtained by acid hydrolysis using HCL at both 8N and 6N for 18 and 24 hrs respectively. Powders retained at 150µm sieve were used for the characterization of the MCS obtained. The amylose and amylopectin fractions, particle size, ash value, true density, powder porosity, hydration capacity, moisture sorption capacity, loss on drying, bulk density, tapped density, Carr’s index, Hausner’s quotient, flow rate and angle of repose were used for the physico-chemical characterizations and subsequently compared with unmodified maize and cassava starches. MCS obtained from maize and cassava showed reduced powder porosity and moisture sorption capacity with an increased amylopectin fraction, hydration capacity, swelling capacity and loss on drying as compared to their unmodified forms. Generally, MCS obtained from cassava showed better flow and packing properties as evident from its Carr’s index, flow rate and angle of repose values as compared to those obtained from maize.

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">Key words: microcrystalline starch, maize starch, cassava starch, acid hydrolysis.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Several physical, chemical and enzymatic modifications have improved the functional properties of starch allowing a wide range of applications. The term microcrystalline starch was probably first used by the famous starch chemist Roy, L.Whistler (1992). By the term microcrystalline starch, as used herein, are meant the starch products obtained by the action of acids on starch granules, below the gelatinization temperature. All granular starch is suitable as starting materials for the manufacture of microcrystalline starch. The history of acid modification can be traced as far back as Linter (1886) who was the first to describe the preparative properties of a material meeting the forgoing definition of acid modified starch. Naegeli (1874), had previously formed the defined product during the early stages of acid treatment, but the final undissolved material (amylodextrin) consisted of a highly fragmented granules. In 1897, Bellmas obtained a German patent for a method differing from that of Linter by the use of a more dilute acid at higher temperature for a shorter time. Duryea (1902) independently discovered much the same variation of Linters method. The modern method of producing acid modified starch on a large scale for industrial uses is essentially the same as that described by Belmas (1897) and by Duryea (1902). More recently, acid modified starches have been developed for various purposes. This includes use of microcrystalline starch products as tableting excipients by Buwalda and Willemina (1997), Acid degradation of starch, the effect of acid and starch type was evaluated by Singh and Ali (2000), The effect of acid treatment on the consolidation and plasto-elasticity of tapioca powder was evaluated by Florence and Roland (2002), and also, The physiochemical properties of sago starch modified by acid treatment in alcohol by Yiu et al (2008), but just to mention a few.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In this work, the physicochemical and flow properties of microcrystalline starch obtained from maize and cassava by acid hydrolysis were investigated and subsequently, unmodified maize starch (MS) and cassava starch (CS) were used for comparison.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ethanol (96%), iodine crystals and glycerol (BDH, England) Xylene (Avondale lab, England), Concentrated hydrochloric acid and sodium hydroxide (May and Baker, England). The maize and cassava tubers were collected in Zaria farms and identified by the institute of agricultural research; Ahmadu Bello University, Zaria, Kaduna state, Nigeria and the extraction of the starches were carried out using the method of Linus (1995).

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PRODUCTION OF MICROCRYSTALLINE STARCH.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Production of microcrystalline starch was carried out as described by Buwalda and Willemina (1997). 450g of an aqueous suspension of starch (36% w/v starch) was poured into a double walled reaction vessel. To this suspension, 28ml, 6N and 8N HCL was added drop-wise with stirring. Subsequently the reaction was conducted for 18 and 24 hrs respectively at 50oC. After cooling, the microcrystalline starch product was separated from the reaction medium by vacuum filtration. On the filtrate, the separated starch product was washed 1:1 with water, then the starch product was suspended again in 250ml water and brought to pHundefined6 with sodium hydroxide solution. The starch product was separated by means of vacuum filtration with 750ml water. A sample of 100g of the wet starch product separated by filtration was suspended in 800ml ethanol and stirred for 30 minutes. Subsequently, the starch product was separated by filtration and dried in Gallenkamp hot air oven at 40oC for 6hrs. The dried starch was ground to fine powder and those fraction retained on 150mm sieve were used for further studies.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PHYSICOCHEMICAL PROPERTIES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The organoleptic characteristics, identification, solubility, total ash determination, and loss on drying were carried out in accordance with British Pharmacopoeia specification

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MICROSCOPICAL DETERMINATION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A small quantity of the starch was mounted on a slide in glycerol. The size of the starch grains was measured using the calibrated eyepiece micrometer and the starch grains observed for 500 particles using an optical microscope (Fisher science apparatus, China).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">DETERMINATION OF AMYLOSE AND AMYLOPECTIN FRACTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This was carried out as described by Gilbert and Spragg, (1964). 5ml of 10% w/v aqueous slurry of starch and 55ml of 0.16M sodium hydroxide was introduced into a flask and swirled gently until the suspension clears. After 5 minutes, 15ml of 5% v/v sodium hydroxide in 0.6M hydrochloric acid was added and mixed gently but thoroughly. The precipitate was harvested by centrifugation at 10,000 rpm for 15min using (hermle Z230) centrifuge. The supernatant was saved in a separate flask and the precipitate was washed by resuspending it in 20ml of 1% sodium chloride and recentrifuging after standing overnight. The original supernatant contains amylose, which is precipitated by saturating it with 1-butanol and letting it stand for two hours and collected by centrifugation at 5,000 rpm for 15 minutes. The precipitate was then dried in a Gallenkamp oven at 40oC and weighed.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">TRUE DENSITY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The true densities (Dt) of the starch was determined by the liquid displacement method using xylene as the immersion fluid and computed according to the following equation,

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">             Dt = w/[(a + w) – b] x SG. ……………. (1)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Where w is the weight of powder, SG is specific gravity of liquid, a, is weight of bottle + liquid and b is weight of bottle + solvent + powder.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">HYDRATION CAPACITY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The method of Kornblum and Stoopak (1973) was used. A 1gm each of the samples was placed in each of four 15ml plastic centrifuge tubes and 10ml distilled water was added from a 10ml-measuring cylinder and then Stoppard. The contents were mixed on a vortex mixer for 2min. The mixture was allowed to stand for 10min and immediately centrifuged. The supernatant was carefully decanted and the sediment weighed. The hydration capacity was taken as the ratio of the weight of the sediment to the dry sample weight.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">SWELLING CAPACITY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This was determined at the same time as the hydration capacity determination using the method of Okhamafe et al (1991) and computed according to the following equation:

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">                      S = (V2-V1)/ V1 x 100 % …………………. (2)

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Where S is the % swelling capacity, V2 is the volume of the hydration or swollen material and V1 is the tapped volume of the material prior to hydration..

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MOISTURE SORPTION CAPACITY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> 2g of the starch material was accurately weighed and evenly distributed over the surface of a 70mm tarred Petri dish. The sample were then placed in a large desiccator containing distilled water in its reservoir (RH = 100%) at room temperature and the weight gained by the exposed samples at the end of a five day period was recorded and the amount of water sorbed was calculated from weight difference.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">FLOW PROPERTIES

<p style="margin: 0cm 0cm 0.0001pt -27pt; text-align: justify; line-height: normal;">           BULK AND TAPPED DENSITIES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> A 10g quantity each of the powder samples was placed in a 50ml clean, dry measuring cylinder and the volume Vo occupied by each of the samples without tapping was determined. After 500 manual taps, occupied volumes, V500 were determined. The bulk and tapped densities was calculated as the ratio of weight to volume (Vo and V500 respectively). The Carr’s index and Hausner’s ratio were determined from the values of the bulk and tapped densities results obtained above.

<p style="margin: 0cm 0cm 0.0001pt -27pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt -27pt; text-align: justify; text-indent: 27pt; line-height: normal;">POWDER POROSITY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This was derived from the values of true and bulk densities when fitted into the equation according to the method of Ohwoauvorhua et al (2004):

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<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">                   e = 1-Bb/Dt x 10 ………………………….. (3)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Were Bb, is the bulk density, Dt is the true density and e is the porosity.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">ANGLE OF REPOSE

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The static angle of repose, a, was measured according to the fixed funnel and free standing cone method and the tangent of the angle of repose calculated using the equation:

<p style="margin: 0cm 0cm 0.0001pt 72pt; text-align: justify; text-indent: 36pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 72pt; text-align: justify; text-indent: 36pt; line-height: normal;">              Tan a = 2h/D …………………………. (4)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Where h is the height of the heap of powder and D is the diameter of the base of the heap of powder.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">FLOW RATE TESTS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The time taken for 50g of the samples to pass through the orifice of an Erweka granule flowability tester (Erweka type GDT, Erweka apparatebau GmbH, West Germany) was determined and the mean recorded.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSION

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-indent: -63pt; line-height: normal;">TABLE 1: Some physico-chemical properties of unmodified   and microcrystalline starches.

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-indent: -63pt; line-height: normal;"> <p style="margin-bottom: 0.0001pt; line-height: normal;">               *value is mean and standard deviation is in parenthesis, number of replicate = 3

<p style="margin-bottom: 0.0001pt; line-height: normal;">KEY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">M-MCS6 = MCS derived from maize with 6N hydrochloric acid in 24 h, M-MCS8 = MCS derived from maize with 8N hydrochloric acid in 18 h, C-MCS6 = MCS derived from cassava with 6N hydrochloric acid in 24 hC-MCS8 = = MCS derived from cassava with 8N hydrochloric acid in 18 h

<p style="margin: 0cm 0cm 0.0001pt 72pt; text-indent: -72pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 72pt; text-indent: -72pt; line-height: normal;">TABLE 2:    Flow and packing characteristics of unmodified and microcrystalline   starches.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">FIG. 1.0:     Percentage cumulative frequency              FIG. 2:        Percentage cumulative frequency

<p style="margin-bottom: 0.0001pt; line-height: normal;">(undersize) versus particle size for MS, M-MCS6        (undersize) versus particle size for CS, C-MCS6

<p style="margin-bottom: 0.0001pt; line-height: normal;"> and M- MCS8. and C-MCS8.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The unmodified starches gave a blue black coloration with iodine solution while the modified samples of both starches gave a slight reddish blue coloration with iodine. This can be attributed to a decrease in the amylose content of all starch samples after hydrolysis. This conforms with Iniberty et al (1988), who say that single helix amylose is responsible for the characteristics binding of amylose to chain of charged iodine molecules. As seen in table 1, Microscopical examination revealed a corresponding decrease in mean particle size with longer duration of acid hydrolysis with cassava starch and its modified products showing lesser and reduced particle size than maize starch and its modified forms. As seen in fig. 1 and 2, the reduction of particle sizes of starch particles on hydrolysis is attributed to the depolymerization of the starch granules The ash value and loss on drying of all starch samples passed the specification values as stipulated by the British pharmacopoeia (2003), The lower value of loss on drying seen with maize starch and its modified product as compared to cassava starch and its modified products could be due to resistance of water entrance in maize starch as compared to cassava starch which is due to intramolecular hydrogen bonding in the amylose content of maize (Rocha et al, 2005). Maize starch granules besides offering more resistance to gelatinization do not have a granular structure for water retention as compared to cassava starch (Rocha et al, 2005).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Swelling which is generally accepted as an indication of tablet disintegration ability can be assessed by the determination of hydration capacity, swelling capacity and moisture sorption profile (Caramella, 1991). The hydration capacity value obtained as shown in table 1 shows that the modified starches have the ability to absorb more water than its unmodified starches for both maize and cassava. The swelling capacity, which reflects the increase in volume of starch following water absorption increased with modification of the starches, with cassava starch and its modified products showing more capacity to swell as compared to maize starch and its modified forms. Thus, if the starches were incorporated in tablet formulation as a disintegrant, it would probably produce tablets disintegration by two mechanism, capillary or wicking due to interparticulate water and swelling in the order of its swelling ability. The powder porosity observed from table 1 shows that porosity reduces with hydrolysis of the starches. This could be attributed to the densities of the starches, its particle sizes and particle shape (Keith, 1976), hence, it would be expected that maize and its modified forms would act more as a disintegrating agent due to its higher value of porosity as compared to cassava and its modified products (Keith, 1976). The moisture sorption capacity is a measure of the moisture sensitivity of the materials. The crystalline portion of starches does not absorb water and the extent of water absorption is proportional to the amount of amorphous portion present (Stamm, 1969). From table 1 it can be seen that the modified starch of maize and cassava showed lesser moisture sorption content than their unmodified forms. This could be attributed to an increase in crystalline portion of the starches after acid hydrolysis. The flow properties of a powder are essential in determining its suitability as direct compression excipients. The angle of repose, Hausner and Carr’s indices are considered as indirect measurement of powder flowability (Staniforth, 1996). High angle of repose is

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">indicative of poor flow while the Hausner index is indicative of interparticle friction; the Carr’s index shows the aptitude of a material to diminish in volume (Staniforth, 1996). As the value of these indices increases, the flow of the powder decreases. In general, however, Hausner ratio greater than 1.25 indicates poor flow; Carr’s index below 16% indicates good flowability while values above 35% indicate cohesiveness (Staniforth, 1996).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Carr’s index is affected by the Particle shape, surface characteristics, particle size, size distribution and the packing configuration adopted by the powder during the bulk densities determination. Therefore, a low Carr’s index would imply a good initial packing arrangement, with less volume of voids. From table 2, it can be seen that the modified starches of both maize and cassava showed better flow properties as compared to their unmodified forms. Cassava and its modified products showed generally better flow than maize and its modified counterpart. In general, maize and its modified products can be said to have poor flow properties in view of its value of angle of repose, flow rate and Hausner ratio which are above the recommended value for a powder with good flow but on the other hand, cassava and its modified products showed better and good flow characteristics of powder as seen in table 2 with Hausner ratio below 1.25, flow rate between 6.31 – 10.0 (g/s) and angle of repose below 15.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSIONS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Microcrystalline starch (MCS) from both maize and cassava showed better properties as compared to their parent starches. MCS obtained from maize and cassava showed reduced powder porosity and moisture sorption capacity with an increased amylopectin fraction, hydration capacity, swelling capacity and loss on drying as compared to their unmodified forms. Generally, MCS obtained from cassava showed better flow and packing properties as evident from its Carr’s index, flow rate and angle of repose values as compared to those obtained from maize.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">References

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Belmas, B. (1897). German patent 110, 957 (cited from: starch: chemistry and technology, vol. 11, Edited by R.L.Whistler and F. Paschal, 1967 Edition; 227).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">British pharmacopoeia (2003). HMSO, London.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Buwalda, P.L. and Willemina, A.A. (1997). Use of microcrystalline starch products as tableting excipients. U. S. Patent WO/1997/031627.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Caramella, C. (1991). Novel methods for disintegrant characterization, part 1. Pharm technol. pp 48-56.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Duryea, C.B. (1902). USA patents 675, 822 (1901) and 696, 949 (1902) (cited from: starch: chemistry and technology, Edited by R.L.Whistler and F. Paschal, 1967 Edition; Vol. 11, pp 227).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Florence, E.E. and Roland, S.O. (2002). Effect on acid treatment on the consolidation and plasto-elasticity of tapioca powder. ''Trop. J. of pharm. Research'', 1(1); 45-49.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Gilbert, G.A. and Spragg, S.P. (1964). Starch: Methods in carbohydrate chemistry,(ed. By R.L Whistler), Vol. IV, pp 25-27.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Imberty, A., Chanzy, H. and Perez, S. (1988). The double-helical nature of the crystalline part of A- starch, ''J. Mol. Biol'', 201: 365-378.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Keith, M. (1976). Compression and consolidation of powder solids in: the theory and practice of industrial pharmacy, second edition. Pp 66-98.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Kornblum, S.S. and Stoopack, S.B. (1973). A new tablet disintegrating agent: cross-linked polyvinyl pyrolidone, ''J. Pharm. Sci''., 62 (i): 43-48.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Linus, A.J. (1995). Tableting behavior of some depolymerize local starches M.SC (Pharmaceutics) thesis work, Ahmadu Bello University Zaria Nigeria Pg 42-45

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 11 - 17, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Linter, C.J. (1886). ''J. Prakt. Chem.., 34: 378 (cited from: starch: chemistry and technology'', vol. 11, Edited by R.L.Whistler and F. Paschal, 1967 Edition; 227).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Naegeli, W. (1874). ''Ann. Chem''. 173: 218 (cited from: starch: chemistry and technology, vol. 11, Edited by R.L.Whistler and F. Paschal, 1967 Edition; 227)

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ohwoavworhua, F.O., Kunle, O.O. and Ofoefule, S.I. (2004). Extraction and characterization of microcrystalline cellulose derived from Luffa cylindrical plant. ''Afri.j.pharm. res.dev''. 1 (1):1-6

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Okhamafe, A.O., Igboechi, A. and Obaseki, T.O. (1991). Celluloses extracted from groundnut shell and rice husk, preliminary physiochemical characterization. ''Pharm. World j''. 8 (4): 120-130.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Rocha, G., Moore, P., Rodriguez, L., Amante, E.R. and Soldi, V. (2005). Cassava and corn starch in maltodextrin production, quimnica nova, Sao Paulo, vol 28(4).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Singh, V. and Ali, S.Z. (2000). Acid degradation of starch, the effect of acid and starch type. ''Carbohyr. Polym''., 41: 191-195.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Stamm, A.F. (1969). Wood and cellulose science. The Ronald press company, New York. Pp 132-165.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Staniforth, J.N. (1996). Powder flow. In: ''Aulton ME (Ed). Pharmaceutics- the science of dosage form design''. Churchill Livingston, pp 600-615.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Whistler, R.L. (1992). U.S. Patent, WO/1992/021703.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Yiu, P.H., Loh, S.L., Rajan, A., Wong, S.C. and Bong, C.F.J. (2008). Physiochemical properties of sago starch modified by acid treatment in alcohol. American journal of applied science, 5(4); 307-311.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/04/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/04/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; line-height: normal;">Achor, M

<p style="margin-bottom: 0.0001pt; line-height: normal;">Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria

<p style="margin-bottom: 0.0001pt; line-height: normal;">Email: [mailto:Munchors001@yahoo.com Munchors001@yahoo.com]

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010                                           ISSN: 2141 - 4149

<p style="text-align: justify;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">A TEN YEAR STUDY OF MANAGEMENT OF CHRONIC HEART FAILURE IN A TERTIARY HOSPITAL IN THE SOUTH WEST NIGERIA.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode1., Ogunbayo, Olufunke O1 and Fasanmade, Adesoji A2.

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">1Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan.

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: -36pt; line-height: normal;">2Department of MedicineUniversityCollegeHospitalIbadan.

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<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">ABSTRACT

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">Chronic Heart Failure (CHF) occurs when the heart is incapable of maintaining sufficient blood flow to accommodate tissue perfusion and metabolic requirements. A retrospective study of ten years of management of chronic heart failure (CHF) at the University College Hospital Ibadan was made. The primary aim of this study was to assess the rational pharmaco-therapeutic approach in the management of chronic heart failure at the University College Hospital Ibadan during a period of ten years. A total number of 202 case notes in the medical records of the outpatients and inpatients of the Cardiology Unit were reviewed. The study population was made up of 109 males (54%) and 93 females (46%). The mean age of subjects was 56.01 years ( + 14.74). A review of the drug management indicated that the prescribed drugs included; loop diuretics 176 (87.1%), thiazide diuretics 19 (9.4%), potassium sparing diuretics 162 (80.2%), amiloride and hydrochlorothiazide 71 (35.1%), digoxin 33 (16.3%), captopril 13 (6.4%), lisinopril 109 (54.0%), enalapril 42 (20.8%), ramipril 28 (13.9%), antibiotics 140 (69.3%), antiplatelet 128 (63.4%), anticoagulant 17 (8.4%), calcium channel blocker 68 (33.7%), methyldopa 46 (22.8%), beta blocker 16 (7.9%), enalapril and hydrochlorothiazide 19 (9.4%), oral hypoglycemic agent 6 (3.0%), non-steroidal anti-inflammatory drugs (NSAIDS) 37 (18.3%), while other prescribed drugs was 148 (73.3%). Side effects documented include cough 32 (15.8%), dyspnoea 9 (4.5%), pain 37 (18.3%), headache 11 (5.4%), hypotension 5 (2.5%), gastrointestinal effects 24 (11.9%), visual effects 4 (2.0%), insomnia 32 (15.8%), tinnitus 3 (1.5%), paraesthesia (18) (8.9%), itching (10) (5.0%), and other side effects 27 (13.4%). Drug tolerability could not be inferred solely from the documented side effects because some might be an extension of the signs and symptoms of chronic heart failure. Clinical laboratory tests and drug interaction should be properly monitored to ascertain rational pharmaco-therapy in the management of chronic heart failure. The findings from this study will positively enhance the long-term management of patients with chronic heart failure in this environment.

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">KEYWORDS: Chronic heart failure, Patients, Management, Pharmacotherapy, Side                                effects.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Chronic heart failure, (CHF) can be defined as progressive complex clinical syndrome characterized by dyspnea, fatigue and fluid retention (Paul et al.,2000). Over the course of the syndrome, patients may not always have symptoms of congestion. Therefore, the term “congestive heart failure” is beginning to fall out of favor; rather, “chronic heart failure” is being used to describe this population (Wendy et al., 2006). It occurs when the heart is incapable of maintaining sufficient blood flow to accommodate tissue perfusion and metabolic requirements. Forty to fifty percent of patients with symptoms of heart failure may have preserved systolic function (Consensus Recommendations for the Management of Congestive Heart Faiure (1999). These patients are more likely to have hypertension, left ventricular hypertrophy (LVH), and isolated diastolic dysfunction (IDD) (Fonarow et al., (2003),. Pook – Wilson (1993).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The final stage in almost any type of heart disease is chronic heart failure (CHF) in which the heart muscle weakens and is unable to pump enough blood to the body(Koristam et al., (1994). In the early stages of CHF, the muscle may enlarge in an attempt to contract more vigorously, but after a time, this enlargement of the muscle simply makes the heart inefficient and unable to deliver enough blood to the tissues (Koristam et al., (1994). In response to this shortfall, the kidneys conserve water in an attempt to increase blood volume and the heart is stimulated to pump harder. Eventually, excess fluid seeps through the walls of tiny blood vessels and into the tissues (Criteria Committee, New York Heart Association Inc (1994). Fluid may collect in the lungs,

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode et al.,: Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">making breathing difficult, especially when patient is lying down at night. Many patients with CHF find it very difficult to do physical activity (Dracup, et al.,1994).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Almost any condition that overworks or damages the heart muscle can eventually result in CHF (Koristam et al., (1994). The most common cause of CHF is coronary heart disease (Dracup, et al.,1994). It may develop when the death of heart muscle in a heart attack leaves the heart with less strength to pump blood, or simply as a result of long-term oxygen deprivation due to narrowed coronary arteries9. Hypertension or malfunctioning valves that force the heart to work harder over extended periods of time may also lead to CHF European guidelines for the diagnosis and treatment of chronic heart failure (2001). Viral or bacterial infections, alcohol abuse, and certain chemicals including some lifesaving drugs used in cancer chemotherapy can all damage the heart muscle and result in CHF (Coats, 1998).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Despite its ominous name, CHF can sometimes be reversed and can often be effectively treated for long periods with a combination of drugs (Fleg et al., (1989). . Addressing possible underlying causes of CHF is the first step in the management of the disease. Non-drug interventions are important, including dietary changes such as reducing salt and alcohol intake and exercise and smoking cessation (Coats, 1998). The principal aims of drug therapy are to reduce mortality, control symptoms, prevent hospital admissions, delay disease progression and minimize the adverse effects of therapy (Fleg et al., (1989). .

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Medications such as Digitalis are often prescribed to increase the heart’s pumping efficiency, while B-blockers may be used to decrease the heart’s workload. Drugs known as vasodilators relax the arteries and veins so that blood encounters less resistance as it flows. Diuretics stimulate the kidneys to excrete excess fluid (Salpeter et al., (2002),( Self et al.,(2003)..

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A last resort in the treatment of CHF is heart transplantation, in which a patient’s diseased heart is replaced with a healthy heart from a person who has died of other causes (O’Connel and Briston (1994). The purpose of this study was to assess the rational pharmaco-therapeutic approach in the management of chronic heart failure (CHF) at the University College Hospital Ibadan in Nigeria during the period of 1995 to 2005 with the goal of providing and enhancing pharmaceutical care.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PATIENTS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A ten-year retrospective cohort review of the 202 case notes from the Medical Records Department of the University College Hospital, Ibadan, in Southwestern Nigeria was made.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The case notes reviewed were randomly selected. Each patient’s case note which outturned the patient’s medical profile was reviewed. The study populations of 202 patients were outpatients and inpatients at the Cardiology Unit who had continuously registered at the University College Hospital, Ibadan between August 1995 and August 2005.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The New York heart association (NYHA) definition was used to define chronic heart failure (Paul et al.,2000).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The past medical history of the subjects was used to elicit the presence of prior myocardial infarction, hypertension, valvular disease, kidney disease, liver disease and other co-morbidities. The drug management was reviewed by noting the types of drugs prescribed, documentation of lifestyle modification such as restricted diet and exercise programmes. Demographics of subjects (age and sex) were collected. The range of the reported adverse reactions was used as a measure of the tolerability to the regimen.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Statistical analysis was done using the SPSS version 11.0 software programme for frequency distribution and cross-tabulations. Test for statistical significance included chi-square for categorical data and bivariate regression to model predictor-criterion relationships.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Permission to conduct the study was given by the authorities of the University College Hospital (U.C.H.) Ibadan, Nigeria. Ethical approval was granted based on the understanding that the study has the potential to improve the overall pharmaceutical care received by the chronic heart failure patients at the University College Hospital Ibadan in particular and Nigeria in general.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode et al.,: Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Two hundred and two case notes of patients diagnosed to have CHF were reviewed. One hundred and nine (54%) were males while ninety three (46%) were females as shown in Figure 1. The mean age was 56.01 years, (S.D + 14.74). Of the two hundred and two subjects 34.7% of the patients had diabetes mellitus, 37.6% were hypertensive, 5% had vascular disease, 8.9% had kidney disease, 5.9% had liver disease, 6.4% had myocardial infarction and 4.5% had corpulmonale. Analysis of the medication subjects were on showed that; 87.1% were on loop diuretic, furosemide, with the most common dosage being between 40 – 80mg daily, 19% were on thiazide and hydrochlorothiazide (25mg twice daily), 80.2% on aldosterone antagonist and spironolactone (25mg twice daily), 35.1% on potassium-sparing diuretic, amiloride combined with hydrochlorothiazide (1 tablet daily). Fig. 2 shows the number of patients who were on loop diuretics to be 176 (87.1%) while patients who were on thiazide diuretics, spironolactone and amiloride + HTZ were 19 (9.4%), 162 (80.2%) and 71 (35.1%) respectively. The number of patients who were not on loop diuretics 26 (12.9%), thiazide diuretics 183 (90.6%), spironolactone 40 (19.8%) and amiloride +HTZ 131 (64.9%) is also shown in Fig. 2. At one point or the other, 16.3% of the patients were placed on digoxin while 6.4% of the patients were prescribed captopril, 54% on lisinopril, 20.8% on enalapril, 13.9% on ramipril and 9.4% on enalapril and hydrochlorothiazide.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Additional therapies used included antibiotics (69.3%), antiplatelets (acetylsalicylic acid) (63.4%), and anticoagulant (8.4%) while 29.7% of the patients were on anti-hypertensive. The calcium channel blockers were given to 33.7% of the patients, methyldopa to 22.8%, beta blocker to 0.99%, oral hypoglycaemic agent (OHA) to 6%, non steroidal anti inflammatory drugs (NSAIDs) to 18.3% and chlorpheniramine maleate, diazepam and antacids to 73.3%.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Side effects recorded included; cough (15.8%), dyspnoea (4.5%), arrhythmia (0%), pain (18.3%), headache (5.4%), hypotension (2.5%), gastro-intestinal effects which includes abdominal pain, nausea, vomiting, loss of appetite (11.9%),  blurred vision (2.0%), insomnia (15.8%),  tinnitus (1.5%),  paraesthesia (8.9%), itching (5%) and other effects such as irrational behavior, palpitation, tiredness, somnambulism, fatigue and tremor were (13.4%). A list of observed side effects is shown in Table 4. The regression of the ACEI on cough as side effect was not significant (P>0.05) as analyzed from the data obtained as shown in Table 5. Similarly the regression of the loop diuretics on tinnitus as a side effect was not significant (P.0.05) as shown in Table 6 and the regression of enalapril on liver disease as a side effect was not significant (P>0.05) as analyzed from the data obtained in Table 7.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Proper management of CHF should include attempts to modify or correct systemic diseases causing or precipitating CHF in approximately 90% of patients15. Coronary artery disease, (CAD), is the cause of CHF in approximately two-thirds of CHF patients in the United States15CAD, if present, may impair ventricular function that may be secondary to myocardial infarction. Among the cardiovascular co-morbidities reviewed in this study, it is clear that hypertension (37.6%) predisposed patients more to CHF. In addition to hypertension other cardiovascular co-morbidities reviewed were valvular disease (5%) and acute myocardial infarction (3.5%) as shown in Table 1.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Hypertension, valvular disease and acute myocardial infarction had been established among the generalized pathophysiologic conditions that lead to CHF. Hypertension causes CHF due to pressure overload of the heart, while acute myocardial infarction leads to CHF due to loss of functional myocardial tissue and valvular disease cause CHF due to volume overload of the heart (Wendy et al., 2006). Hypertensive patients may benefit from the same antihypertensive drugs used to treat CHF while patient with acute myocardial infarction may benefit from beta blockers and patient with valvular disease may benefit from attempt to surgical repair or replacement of defective myocardial valves (Eichhorn and Hjalmarsom (1994).undefinedIn this study 202 case notes consisting of 54% males and 46% females were reviewed. The random selection of case notes is supported by a study carried out in 2002 in the United States of America where the prevalence of CHD was estimated to be 4.9 million with nearly equal number of men and women (Felker et al (2004).. The Kidney is one of the target organs that are complicated in arterial hypertension. Untreated hypertension resulting from renal complication can result in CHF (Wendy et al., 2006). Diabetes mellitus is a major cardiovascular risk factor in hypertension that complicates CHF (Wendy et al., 2006). In this study, renal disease 8.9% and diabetes mellitus 34.7% were co morbidities. The influence of some drugs such as captopril, lisinopril, ramipril and enalapril, which are angiotensin converting enzyme inhibitors (ACEI) on the kidney function, could be quite significant. Proper electrolyte and urea concentrations (E&U) tests should be carried out to monitor the kidney function. Ideally,

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">E&U test should be done before and during treatment (Eichhorn and Hjalmarsom (1994).undefinedReduction in renal blood flow and glomerular filtration rate (GFR) are reflected by increases in both serum creatinine concentration and blood urea nitrogen (BUN) level. In this study, it was noted that the test, when carried out, was recorded once, most times before commencing the treatment which made it difficult to determine to what extent the kidney was compromised prior to therapy as well as determine if the observed kidney problem was as a result of drug use or deteriorating co-morbidity.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Numerous laboratory abnormalities are observed in patients with CHF. Simple laboratory abnormality tests such as serum electrolytes, serum creatinine and blood urea nitrogen, body weight and chest radiographs are used most frequently in monitoring ambulatory patients with CHF. The patient can monitor body weight at home every day and serum electrolytes are checked about every 1 to 2 months provided that there are no changes in therapy.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In this study, the conventional treatment for CHF was a combination of a diuretic most especially a loop and a potassium-sparing diuretics. Loop diuretics was 87.1%, thiazide 9.4%, spironolactone, an aldosterone antagonists 80.2% while, 35.1% were prescribed amiloride and hydrochlorothiazide, 6.4% were prescribed captopril, 54% lisinopril, 20.8% enalapril, 13.9% ramipril and 9.4% enalapril and HTZ as a fixed dose as shown in table 2.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">As the understanding of the pathophysiology of CHF has developed, there have been a number of major advances in its pharmacotherapy. The evidence-based drug used in improving CHF includes ACEIs, beta-blockers and spironolactone (Zerembski et al., In Press),. ACEIs have been described as the cornerstone of CHF management and have been shown to significantly reduce mortality, and morbidity. Based on several studies, ACEIs are to be considered for all patients with symptoms of CHF that result from left ventricular dysfunction.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In this study, a good number of the patients diagnosed with CHF were prescribed ACEI. This is in line with the current guideline recommending the use of ACEI as first line therapy (Wendy et al., 2006).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Products incorporating an ACEI with thiazide diuretics are now available. (for example Enalapril and HTZ). In this study 9.4% of such was on ACEI with thiazide diuretics. The use of this combination product should be reserved for patient whose blood pressure has not responded to thiazide diuretic or an ACEI alone.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Despite publication of data as early as 1979 to support the use of beta-blockers, many clinicians have been reluctant to use them in the management of CHF. As observed also in this study, 7.9% patients were prescribed beta-blocker, such as atenolol. Large-scale studies were however published in the late 1990s demonstrating significant reduction in mortality during treatment with beta-blockers. For example, in their second report, the Cardiac Insufficiency Bisoprolol study II (CIBIS-II) randomized 2,647 patients to receive either bisoprolol or placebo in combination with standard care ACEI with or without diuretic and/or digoxin. Bisoprolol treatment was associated with 34% reduction in mortality, a 32% reduction in hospital admission and significant improvements in symptom control. These benefits were evident across all the subgroups assessed including people with diabetes, the elderly and those with renal dysfunction (Tsuyuki et al.,(1995)..

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Most of previously published reports have studied the benefit of beta-blockers in patients with New York Heart Association (NYHA) class II or III, heart failure. There has been some controversy over the benefit and risk associated with treating patients with more severe symptomatic NYHA class IV. This subgroup of patients was investigated in the Copernicus trial, which reported an overall reduction in mortality of 35% with carvedilol treatment compared to placebo (Elkayam et al., (1998)..

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Copernicus indicated that this agent could be prescribed safely to patients with an EF<25% with 74% achieving target dose and the majority reporting significantly improved symptoms. A 23% reduction in mortality was reported in Copernicus study looking at Carvedilol therapy in patient with left ventricular dysfunction, post-myocardial infarction (PMI), indicating that the beta-blockers are safe and effective in PMI (Scognamiglio et al., (1994).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">B-blockers should therefore be considered for all patients with NYHA class II, III or IV heart failure. This agent should be initiated when patients are clinically stable and optimized on first line therapy primarily by ACEI and diuretic. B-blocker therapy must not be initiated during the acute phase of CHF management, but may be

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">considered in the hospital environment when symptoms of fluid overload have been adequately addressed (Zerembski et al., In Press).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">B-blockers are contra-indicated in patients with severe bradycardia, acute CHF, severe asthma or bronchospasm and peripheral vascular disease. Although the Committee of Medicines has warned against the use of B-blockers in patients with a history of asthma or bronchospasm, a recent Cochrane Collaboration Review has concluded that there is no strong evidence to support withholding cardio selective b-blockers from patients with mild to moderate reversible airway disease (Wendy et al., 2006, Paul et al.,2000)..

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Spironolactone therapy is indicated for the treatment of NYHA class IV heart failure or class III heart failure where there has been a recent class IV episode and it should be added to optimized ACEI therapy. There is, however, little data on the use of ACEI, beta-blocker and spironolactone combinations currently. In this study, 80.2% patients were prescribed spironolactone as shown in Table 2. Spironolactone is contraindicated in hyperkalaemia, hyponatraemia and Addison’s disease. Again the importance of carrying out the electrolyte level test is emphasized. Renal function and serum potassium should be monitored carefully throughout therapy.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Oral digoxin is clearly indicated in patients with atrial fibrillation and CHF for the control of ventricular rate. Although there is no overall mortality benefit conferred by digoxin therapy in patient with normal sinus rhythm; trial data indicate improved symptom control and reduced hospital admission, at the expense of an increase in cardiac arrhythmia (Helen Williams and Mark Kearney. (2002). Also, the currently limited information on the use of digoxin in CHF patients does not justify its routine use in this setting. Digoxin may therefore be considered for patients who remain symptomatic despite optimized doses of diuretic, ACEIs, beta-blockers and spironolactone (Consensus Recommendations for the Management of Heart (1999), Abraham and Hayes (2003).. In this study 16.3% of the patients were on digoxin, (Table 2). Majority were given for a short period and discontinued.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In CHF, the major defect is a decrease in cardiac output, which results in poor tissue perfusion and stable blood pressure. Neurohormones mainly norepinephrine and angiotensin II by their vasoconstricting effects increase peripheral resistance, decrease cardiac output and heart rate. This is the pathological basis and focal point in the use of vasodilators in CHF. Vasodilator therapy shows new promise in CHF treatment. These agents through with varied mechanisms have been shown to alter the capacitance (preload) and resistance (after load) of vessels, either directly or indirectly (Bakris and Weir (2000).undefinedThese include the calcium channel blockers such as nifedipine, verapamil, diltiazem and amlodipine.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Nifedipine, amlodipine, verapamil and diltiazem have some degree of negative isotropic effect which could worsen the left ventricular function in CHF. Amilodipine is a potent peripheral vasodilator with minimal effect on heart rate. Nifedipine is the most studied of this class of drugs and is indicated in CHF with dilated cardiomyopathy. In this study, amlodopine a calcium channel blocker was prescribed more often (33.7%). Calcium antagonists are useful alternatives in some patients that may have CHF alone or in addition to other cardiovascular diseases such as angina pectoris, arrhythmias, cardiomyopathy and hypertension (Rothlisberger et al., (1994). Since CHF may be worsened by the use of some of these calcium antagonists, patient selection, gradual administration of the drugs and close monitoring should be the guide in the use of these drugs in patients with CHF.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Non-steroidal anti-inflammatory drugs, (NSAIDs), inhibit cyclo-oxygenase activity, leading to a reduction in vasodilatory prostaglandins, which oppose the renal and systemic effects of all the patients with CHF (Feenstra et al (1999).Administering NSAIDs to patients with CHF produces a reduction in glomerular filteration rate (GFR) and renal blood flow and an increase in sodium and water retention. Chronic use of NSAIDs in older adults with CHF is associated with increased hospitalization rates secondary to acute CHF decompensation (Heerdink et al., (1998). In this study, 18.3% were prescribed NSAIDs as shown in Table 3. Improved education about the possible detrimental effects of chronic use of NSAIDs in patients with CHF is important. There is the need to pay more attention to these precipitating factors which could significantly reduce the number of hospitalizations and ease the clinical and economic burden of CHF on patients.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The tolerability of the drugs could not be significantly measured from this study because most of the time they were not documented. A clear distinction could not be made between side effects which were an extension of the signs and symptoms of the diseases conditions or as a result of the drugs as shown in Table 4. The regression

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">of the ACEIs on cough was not significant (P>0.05) as analyzed from the data obtained as shown in Table 5. Similarly, the regression of the loop diuretic on tinnitus as a side effect was not significant (P>0.05) as shown in Table 6. Although not statistically significant it could however be said that the drugs were clinically tolerated by the patients. It is imperative to know the co-morbidities associated with hypertension, being the major risk factor of CHF, so as to rationalize the choice of drug to be prescribed. In this study, it was noted that 41.7% of the patients had liver disease and were prescribed enalapril, a prodrug that has to be metabolized by the liver to the active angiotensin converting enzyme (ACE). The regression of the enalapril on liver disease was however not significant (P>0.05) as analyzed from the data obtained in Table 7. The influence of the medical representatives of pharmaceutical industries on the prescribers was so obvious that too frequent switching from one brand of a particular class of drug product to other classes of drug products was too prominent. It s important however that such switching be based on potential clinical advantage as well as positive effect of the new drug on the quality of life of the patient.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The results of the present work show that drug tolerability could not be inferred solely from the documented side effects because some might be an extension of the signs and symptoms of chronic heart failure. Clinical laboratory tests and drug interaction should be properly monitored to ascertain rational pharmaco-therapy in the management of chronic heart failure. These findings will optimize the treatment of patients with chronic heart failure.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">ACKNOWLEDGEMENTS

<p style="margin-bottom: 0.0001pt; line-height: normal;">We acknowledge the technical support of the Staff in the Cardiology Department of University College Hospital Ibadan and the cooperation of the management of the Hospital.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Tsuyuki R. T., Ave zum A. Yusuf S, (1995). B-blocker therapy for Congestive Heart Failure; a systematic overview (updated) abstract). Paper presented at the Annual meeting of the AmericanCollege of Clinical Pharmacy, WashingtonDC.  August 6 – 9.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Wendy G.S., Paul E.N Jr. and Dawn G.Z (2006). Heart Failure In Textbook of therapeutics Drug and Disease Management. Helms, Quan, Herfindal and Gourley. 8th Ed. 486-528

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Zerembski D. G. Nolati P. E., Slack M. K. Lui C Y, Meta-analysis of the use of low dose-adrenergic blocking therapy in idiopathic and ischemic cardiomyopathy. Am J. Cardiol (inpress).

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode et al.,: Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 1: Co-morbidities associated with chronic heart failure.

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 3: Concomitant drugs prescribed <p style="margin-bottom: 0.0001pt; line-height: normal;">*Multiple responses

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode et al.,: Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 4: Side effects documented among subjects with CHF <p style="margin-bottom: 0.0001pt; line-height: normal;">

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<p style="margin-bottom: 0.0001pt; line-height: normal;">*Multiple responses

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<p style="margin-bottom: 0.0001pt; line-height: normal;">TABLE 5:  Regression of the ACEIs on cough Model summary <p style="margin-bottom: 0.0001pt; line-height: normal;">a. Predictors: (Constant): Enalapril + Hydrochlorothiazide, Ramipril, Captopril, Enalapril, Lisinopril

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<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVAb <p style="margin-bottom: 0.0001pt; line-height: normal;">a. Predictors: (Constant): Enalapril + Hydrochlorothiazide, Ramipril, Captopril, Enalapril, Lisinopril

<p style="margin-bottom: 0.0001pt; line-height: normal;">b. Dependent variable: Cough

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<p style="margin-bottom: 0.0001pt; line-height: normal;">TABLE 6:  Regression of loop diuretic on tinnitus Model summary <p style="margin-bottom: 0.0001pt; line-height: normal;">a  Predictors: (Constant): Loop diuretic

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVAb <p style="margin-bottom: 0.0001pt; line-height: normal;">a   Predictors: (Constant): Loop diuretic, b    Dependent variable: Tinnitus

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Omole, Moses Kayode et al.,: Continental J. Pharmaceutical Sciences 4: 18 - 27, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 7:                Cross tabulation of liver disease and Enalapril Chi-Square tests <p style="margin-bottom: 0.0001pt; line-height: normal;">a. Computed only for a 2x2 table, b.   1 cells (25.0%) have expected count less than 5. The minimu expected

<p style="margin-bottom: 0.0001pt; line-height: normal;">      count is 2.50

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/04/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/04/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; line-height: normal;">OMOLE, Moses Kayode.

<p style="margin-bottom: 0.0001pt; line-height: normal;">Department of Clinical Pharmacy & Pharmacy Administration, Faculty of Pharmacy, University of Ibadan.

<p style="margin-bottom: 0.0001pt; line-height: normal;">E-mail: kayodeomole06@yahoo.com

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 28 - 34, 2010                                           ISSN: 2141 - 4149

<p style="text-align: justify;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">ANTIOXIDANT ACTIVITY IN BARK AND ROOTS OF NEEM (Azadirachta indica) AND MAHANEEM (Melia azedarach)

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Gayatri Nahak and R. K. Sahu

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Department of Botany, B.J.B. (A) College, Bhubaneswar, Orissa

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<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">ABSTRACT

<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">The aim of this study was to investigate the antioxidant activity of the multi-solvent extracts (aqueous, methanolic and ethanolic) of Root and Bark of two Medicinal plant i.e. Azadirachta indica A. Juss and Melia azedarach of Meliaceae family using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) - scavenging assay. The dry powder of Root and Bark of the two neem tree were extracted using soxhlet extraction followed by vacuum rotary evaporator methods. The extracts were tested for antioxidant activity using DPPH-scavenging assay. Total phenol contents of extracts were also determined by folin cicalteu reagent method. Experimental results revealed the highest fraction of crude extract, phenol content as well as antioxidant activity in Barks and Roots of Mahaneem (Melia azedaarach) in comparison to Neem (Azadirachta indica). The total phenolic concentration of Bark, Root of Melia showed a positive correlation with antioxidant capacity. Similarly IC50 values in Bark and Root of Mahaneem was as low as Ascorbic acid. The plant Mahaneem and its plant parts may be exploited for clinical medicine as potent factor because of its high antioxidant activity. (CJBiolSci/2010/018)

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<p style="margin: 0cm 43.2pt 0.0001pt; text-align: justify; line-height: normal;">KEYWORDS: Neem, Mahaneem, Antioxidant activity, Phenol content, Bark and Root.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">It is an established fact that polyphenolic compounds possess remarkable antioxidant activities which are present quite commonly in the plant family Meliaceaeundefined(Siddiqui, et al., 1992; Sultana, et al., 2007), It has also been reported that phenolic contents of neem can be influenced by geographical locations and other abiotic factors (Ermel, et al., 1986; Kaura, et al., 1998; Kaushik, et al., 2007). A. indica is well known in India and its neighboring countries for more than 2000 years as one of the most versatile medicinal plants having a wide spectrum of biological activity''. A. indica and M. azedarach'' are two closely related species of Meliaceae family. The former is popularly known as Indian Neem (Margosa tree) or India lilac, and the latter as Mahaneem or Persian lilac. All parts of the plant have been used for medicinal purposes including fruits, seeds, leaves, roots and barksundefined(Anon, 1985). Neem has been extensively used in Ayurveda, Unani and homoepathic medicine and has become a Synonym of modern medicine. The Neem tree contains more than 100 bioactive ingredients. The most important bioactive compound is azadirichtin. Melia azedarach, the Persian Lilac is popularly known as Mahaneem tree and cultivated in all stations. It is a large evergreen tree found throughout India and very similar to Neem. It is native to upper Burmah region. It’s Flowering time is May-June and Fruiting time is Nov-Dec. The inner bark contains a resinous alkaloid substance and is used as an anthelmintic. Various scientific studies reported the analgesic, anticancer, antiviral, antimalarial, antibacterial, and antifungal, antifeedent and antifertility activity of this plant (Vishnukanta & Rana, 2008)

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Leaf and bark extract of A. indica has been studied for its anti-oxidant activity (Ghimeray, et al., 2009; Sultana, et al., 2007). However anti-oxidant activity of Mahaneem (M. azedarach) another very important medicine plant has not been investigated. In present work bark and root of two trees, A. indica & M. azedarach belonging to family Meliaceae extracted in water, ethanol & methanol were investigated for the presence of phenol content and antioxidant activity in a comparative way.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Chemicals and Reagents'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Folin-Ciocalteu reagent (Merck Pvt. Ltd, India), Sodium chloride (S.D. Fine Chem, India), Sodium carbonet (Merck Pvt. Ltd, India), Catechol (Himedia Lab., India), 2, 2-Diphenyle-2-picryl hydrazyl (DPPH) and Ascorbic acid are obtained from (Himedia Lab., India). Stock solutions of the test extracts were prepared in ethanol. Appropriate blanks were used for individual assays.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Gayatri Nahak and R. K. Sahu: Continental J. Pharmaceutical Sciences 4: 28 - 34, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Plant Materials

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Roots (root with root bark) and Barks of the two species i.e. A. indica & Melia azedarach of Meliaceae family were collected from the Medicinal Garden of B.J.B (A) College, Bhubaneswar, Orissa. The Barks and Roots of two plants were rinsed severally with clean tap water to make it dust and debris free. Then the Barks and Roots were spread evenly and dried. Then the dried samples were ground in electric chopper to get fine powder form for further use.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Instrumentations

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Collection of multi-solvent extract was done by Soxhlet apparatus (J.S.G.W) with varying temperatures according to the B.P. of the solvents. The samples were evaporated through the Rotary vacuum evaporator at 60-1000C according to the B.P. of supplied solvents. Absorbance spectrophotometery was carried out using a UV-vis spectrophotometer (EI, model-1371).Wavelength scans and absorbance measurements were in 1ml quartz cells of 1cm path length.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Preparation of plant extracts

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The dried and powdered Neem and Maha-neem Barks and Roots (each 50g) were extracted successively with multi-solvent extraction by using double distilled water, ethanol and methanol (each 400ml.) for 10-12 h. through Soxhlet apparatus. Then collected solutions were filtered through Whatman No-1 filer paper. The extracts were evaporated to dryness under reduced pressure at 900C by Rotary vacuum evaporator to obtain the respective extracts and stored in a freeze condition at −180C until used for further analysis.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Phenolic Estimation

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The total phenolic content of plant extracts were determined by using Folin-Ciocalteu Spectrophotometric method according to the method describedundefined(Kim, et al., 2007). Reading samples on a UV-vis Spectrophotometer at 650 nm. Results were expressed as catechol equivalents (µg/mg).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Antioxidative activity

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The antioxidant activity of the Neem and Mahaneem (Barks and Roots) on the basis of the scavenging activity of the stable 2, 2- diphenyl-2-picrylhydrazyl (DPPH) free radical was determined according to the method described in (Brand-Williams, et al., 1995) with slight modification. The following concentrations of extracts were prepared 40μg/mL, 80μg/mL, 120μg/mL, 160 μg/mL and 200μg/mL. All the solutions were prepared with methanol. 5 ml of each prepared concentration was mixed with 0.5mL of 1mM DPPH solution in methanol. Experiment was done in triplicate. The test tubes were incubated for 30 min. at room temperature and the absorbance measured at 517nm. Lower the absorbance of the reaction mixture indicates higher free radical scavenging activity. Ascorbic acid was used as a standard and the same concentrations were prepared as the test solutions. The different in absorbance between the test and the control (DPPH in ethanol) was calculated and expressed as % scavenging of DPPH radical. The capability to scavenge the DPPH radical was calculated by using the following equation.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Scavenging effect (%) = (1-As/Ac) ×100

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">As is the absorbance of the sample at t =0 min.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ac is the absorbance of the control at t=30 min.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Effect of Different Solvents on the Yields of Neem and Mahaneem Leaf Extracts

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The significant variation in the yields of Azadirachta and Melia extracts were shown using various fraction solvents. The yield of extracts using Water, Methanol and Ethanol in case of Azadirachta were 3.90gm, 4.45gm and 4.35gm (in Bark) and 3.02gm, 3.45gm and 3.56gm (in Root) respectively. Likewise in case of Melia extract also followed the same order as the Azadirachta extracts, and they were 4.34gm, 5.20gm and 5.85gm (in Bark) and 3.29gm, 3.56gm and 3.29gm (in Root) respectively. The variation in yield may be due to the polarity of the solvents used in the extraction process (Table-1).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Free Radical and Antioxidant Activity

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Table-2 and Table-3 show the results of the free radical (DPPH) scavenging activity in % inhibition in Azadirachta and Melia respectively. The result revealed that the ethanol fraction of Bark in case of Melia exhibited the highest radical scavenging activity with 83.38±0.01 followed by its methanol extract with 72.88±0.04 and aqueous extract with 53.89±0.07. In comparison to Melia the Azadirachta extract shows less

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Gayatri Nahak and R. K. Sahu: Continental J. Pharmaceutical Sciences 4: 28 - 34, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">scavenging activity. The Azadirachta extract of Bark obtained from ethanol shows 66.94±0.02.i.e. highest scavenging activity followed by its methanol extract with 55.00±0.05 and aqueous extract with 37.50±0.03. In overall comparison the ethanolic extract of Bark in both Azadirachta and Melia show the highest scavenging activity followed by the methanol and then aqueous. The results showed that the antioxidant activity of Root extracts of both the plants exhibited decreasing radical scavenging activity as comparison to Bark extracts. The Root extracts of Melia plant obtained from all the three solvent showed little bit higher antioxidant activity as compared to Azedarachta Root extracts. The ethanolic fraction of root in case of Melia plant exhibited highest antioxidant activity i.e. 63.55±0.04 followed by the methanolic fraction i.e. 47.96±0.02 and aqueous fraction i.e. 36.44±0.04. Similarly in case of Azedarachta plant the ethanolic fraction of root extract showed the highest i.e. 50.84±0.03 followed by the methanolic fraction i.e. 42.71±0.04 and aqueous fraction i.e. 30.50±0.04. The Methanol and ethanol has been proven as effective solvent to extract phenolic compoundsundefined(Siddhuraju & Becker, 2003). In the present study, the values of ethanolic and methanolic extracts were higher than those of aqueous ones. Among solvents used in this study ethanol has showed the best effectiveness extracting phenolic components. Ethanol is preferred for the extraction of antioxidant compounds mainly because its lowers toxicityundefined(Karadeniz, et al., 2005) Fig.1. Shows the comparative study of radical scavenging activity between Melia and Azadirachta with respect to Ascorbic acid as standard.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Phenol Content and Antioxidant Activity

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">It is reported that phenols are responsible for the variation in the antioxidant activity of the plant (Cai, et al., 2004). They exhibit antioxidant activity by inactivating lipid free radicals or preventing decomposition of hydroperoxides into free radicals. (Pitchaon, et al., 2007; Pokorny, et al., 2001). Phenolic compounds are considered to be the most important antioxidative components of herbs and other plant materials, and a good correlation between the concentrations of plant phenolic and the total antioxidant capacities has been reported (Madsen, et al., 1996; Pellegrini, et al., 2000). The total phenolic content varied significantly between the two species of Maliaceae family i.e. Azadirachta indica and Melia azedarach. The contents of total phenolic compounds in crude ethanolic extracts obtained from these two Neem plants are presented in Table-1. The results were reported as catechol equivalents (µg/ml). The highest concentration of total phenol was 280µg/ml present in the ethanolic extract of Bark in Melia plant. The methanolic and aqueous fractions of Bark in case of Melia showed 220µg/ml and 160µg/ml of phenol contents respectively. Similarly the Azadirachta the ethanolic extract from Bark exhibited highest phenol contents of i.e.210µg/ml and followed by the methanolic and aqueous fraction 158µg/ml respectively. In our present investigation we found that in both the Neem plants the Bark exhibited the higher amount of phenol content as comparison to Root. The total phenol content in case of Melia Root obtained from ethanol fraction showed highest amount of phenol content i.e. 70µg/ml followed by methanolic fraction 50µg/ml and aqueous fraction i.e. 20µg/ml.Similaly in case of Azedarachta root obtained from ethanol fraction showed highest amount of phenol content i.e. 48µg/ml. followed by methanol fraction 30µg/ml and aqueous i.e. 18µg/ml. Much higher antioxidant activity of the alcoholic preparation have given evident assumption is more useful than the aqueous one in medical approachundefined(Pietta, et al., 1998). Moreover, such a preparation consists more oxindole alkaloids and a larger spectrum of biologically active constituents. High percent of yield and high value of phenol content in ethanolic extracts show that phenolic constituents must be responsible for such properties. It is in agreement with the data of (Goncalves, et al., 2005). It was reported from our previous paperundefined(Nahak and Sahu, 2010), that the ethanolic fraction of Mahaneem leaves exhibited highest i.e. 68±0.03% and it showed a low IC50 value of 0.008µg/ml. There was an increasing concentration of phenol content observed in the root bark of A. indica when compared to the leaf. Also increase in the stem bark of A. indica was observed when compared to the leaf extractundefined(Nahak and Sahu, 2010; Olabinri, et al., 2009). Similar case was also observed in case of Melia azedarach (Olabinri, et al., 2009.) The order of total phenol content for these two neem trees were as follow: stem bark > root bark > leaf. In our present study we found that there is a positive correlation between total phenolic content and antioxidant activity in both the neem plants. Some studies have demonstrated a correlation between phenolic content and antioxidant activity (Yang, et al., 2002).The correlation between total phenolic content and antioxidant capacity in our plant samples is possible owing to the presence of following factors: the antioxidant activity observed in plant extracts may be due to the presence of phenolic compounds or polyphenols or flavonoids or tannins.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> IC50 Value'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">IC50 value is defined as the concentration of substrate that causes 50% loss of the DPPH activity and was calculated by linear regression mentioned of plots of the percentage of antiradical activity against the concentration of the tested compounds. Results showed in Fig.-3 and Fig.-4 show the reports of IC50 values in Neem and Mahneem. It shows that there is no IC50 value in water and methanol extraction of ''Azadirachta ''

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Gayatri Nahak and R. K. Sahu: Continental J. Pharmaceutical Sciences 4: 28 - 34, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">indica. Only ethanolic extract of Azadirachta root showed an IC50 value where as in both ethanolic and methanolic extract of Bark fraction showed no IC50 value. In comparison to Azadirachta, all extracts of Melia showed lower IC50 value in case of Bark extracts, however ethanolic extract of Melia being the lowest (Fig-2). But in case of Root extracts only the ethanolic extract showed the lowest IC50 value. The ethanolic extract of Mahaneem exhibited significant activity with low IC50 value in comparison to Azadirachta. A linear relationship between the reciprocal of IC50 value and the total polyphenol content of Azadirachta and Melia was observed in this study, indicating that increasing the polyphenol content strengths the antioxidant activity. This finding is similar to that reported byundefined(Katsube, et al., 2004).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Conclusion

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">In conclusion, the Bark and Root of Melia azedarach (Mahaneem) proved to be of higher antioxidant potential in comparison to Neem which is a very important medicinal plant like Neem belonging to family Meliaceae. Among the plant parts studied Bark proved to be more useful in terms of antioxidant activity which can be exploited for combating diseases related to oxidative stress.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">ACKNOWLEDGMENT

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The authors are thankful to University Grants Commission New Delhi, for Financial Assistance in form of major research project to one of the author (R.K.S) we are also thankful to Head of the Department of Botany and Principal B.J.B. (A) College for providing necessary facilities for carrying out the experimental work. Finally we are thankful to Debyani Samantray for helping in computer work without which preparation of the manuscript would not have been possible.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Siddiqui BS, Ghiasuddin Faizi S, Siddiqui S, (1992). Triterpenoids from the fresh fruit coats of     Azadirachta indica. Phytochem, 31(12): 4275-4278.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Sultana B, Anwar F, Przybylski R, (2007). Antioxidant activities of phenolic components present in barks of Azadirachta indica, Terminalia arjuna, Acacia nilotica, and Eugenia jambolana Lam.trees.Food Chemistry, 104, 1106-1114''. ''

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Vishnukanta AC & Rana, (2008). Melia azedarach: A phytopharmacological review. Journal of Pharmacogenosy Reviews, 2,173-179.'' ''

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Yang JH, Lin HC, Mau JL, (2002). Antioxidant properties of several commercial mushrooms. Food Chem, 77: 229-235

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<p style="margin: 0cm 0cm 0.0001pt 72pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table-2:  Antioxidant activities of Azadirachta indica in different solvents

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">                  Figure-1:    Antioxidant activity of

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure-2: Antioxidant activity of                                                        Neem and Mahaneem (Root)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Neem and Mahaneem (Bark)

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure-3: IC50 Values of Neem and                                                 Figure-4: IC50 Values of Neem and

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/04/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/04/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; line-height: normal;">R. K. Sahu

<p style="margin-bottom: 0.0001pt; line-height: normal;">Department of Botany, B.J.B. (A) College, Bhubaneswar, Orissa

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Email: [mailto:sahurajani@yahoo.co.in sahurajani@yahoo.co.in]

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 35 - 39, 2010                                           ISSN: 2141 - 4149

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">TOXICITY AND HAEMATOLOGY STUDIES OF THE ROOT BARK OF HYMENOCARDIA ACIDA, TUL (EUPHHORBIACEAE)

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">P.N. Olotu1, H. Ibrahim2,undefinedNundefinedIliyas2 and J.S Gushit 3

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">1Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, University of Jos, Jos, Nigeria.

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">2Department of Pharmacognosy and Drug Development, Faculty of Pharmaceutical Sciences, Ahmadu Bello University Zaria, Nigeria. 3 Department of Science Laboratory Technology, Faculty of Natural Sciences University of Jos, Nigeria.

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<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">ABSTRACT

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">The research work covers the toxicities and haematology studies of the root bark of Hymenocardia acida which is claimed by the Hausa in the Northern Nigeria to be used traditionally for the treatment of headache, chest-pain, rheumatic pain, toothache, ear pain, migraine and sickle cell crisis. The plant was safe orally on acute toxicity investigation on mice. There was no observable LD50. The mice survived even the doses greater than 5000mg/kg and up to 11000mg/kg. The histopathological studies on chronic administration of the root bark in mice fed with 25% w/wof amended diet showed no observable organ damage but the mice fed with 50%w/w amended diet showed a focal area of hepatic necrosis and the globule cells of the intestine were covered with progressive mucin and lymphocyte proliferations were observed with the spleen. This means that the long term use of the plant in traditional practice should be cautioned. Furthermore, the body weight, feed and water-intake increase with the mice fed with the lower concentration of the amended diet (25% w/w) but decreased with the higher concentration (50% w/w) at P<0.05. There was also a prominent change with the post treated mice. This result may suggest the use of the plant for nutritional purposes at lower concentration. Analysis of the blood parameters showed very significant increase with the RBC. This justifies the claim of the plant in the treatment of anaemia. Analysis of the plant on the remaining blood parameters was not significant.

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<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">KEYWORDS: Acute toxicity, Chronic toxicity, Haematology, ''Hymenocardia acida and                   Euphorbiaceae. ''

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<p style="margin-bottom: 0.0001pt; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The plant Hymenocardia acida is a tree of about 6 m high, gnarled and twisted with characteristics rough rusty-red bark, of the wooded savanna throughout the region from Senegal to west Cameroons, and widespread in tropical Africa. The wood is light brown or pink, darkening to orange, close- grained, with conspicuous annual rings, and hard. It has been said to be brittle and good only for firewood. This may be reflected in certain Ivorian names meaning ‘The tree which kills the wife’, i.e. when an unfaithful wife goes to collect firewood, the tree shatters at her tough and a branch pieces her abdomen. (Bouquet and Debray, 1974).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Gbaya of the central African Republic recognize the tree as producing good firewood; indeed classified it as ‘woman’s firewood’ being good for the hearth and cooking place, long- lasting while the house wife is about other chores, yet reviving quickly from sleeping embers, with a hot flame and little smoke (Bouquet, 1969). The tree is used for house- posts in southern Nigeria, and in Gabon where the wood is made into charcoal for blacksmith’s work. In Kenya and in Uganda, the wood is known for its hardness, denseness, durability and good resistance to termite- attack. It is used to make pestles and back- cloth mallets. Charcoal made from the branches is powdered and rubbed on the head for headache in the soudanian region (Burkill, 1985).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The foliage is browsed a little by cattle in Senegal as a supplementary food and in Nigeria. Leaves and leafy shoots have a considerable medicinal use. When chewed, they have an acid taste. Leaves are prepared into infusion for use in Senegal for chest complaints and small- pox and with the roots, for deficiency diseases. A macerate is given for gripe, and leaf- decoction used as an eye wash (Daziel, 1937). A decoction with honey is taken in Guinea for biliousness. In Ivory coast- upper Volta, a leaf- decoction is used in baths and draughts as a febrifuge and leaf- powder is taken as snuff for headache or applied topically for rheumatic pains and toothache, or for the same purposes, leaves may be pulped with an organic acidic substances such as citron juice or sap of Piliostigma reticulatum (leguminosae: caesalpinioideae), (Kerharo, 1974).

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">P.N. Olotu et al: Continental J. Pharmaceutical Sciences 4: 35 - 39, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Justification

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Hausa tribe in the Northern Nigeria has over the years used the decoction of leaves and the stem bark or root bark of Hymenocardia acida in the treatment of pain of various categories such as migraine, sickle cell crisis and menstrual pain (Agishi, 2004). So far, no official work has been done on the toxicity and haematological studies of the root-bark extracts to establish its safety scientifically.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This study aims at establishing the safety of the crude drug with the view of its future development.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Plant Collection and Identification:

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The root bark of Hymenocardia acida was collected from Kudingi village, Zaria, Nigeria. The plant was identified in the field using keys and description given in the official books (Woody Plant of West Tropical Africa). The collection (voucher specimen) was confirmed and authenticated at the Herbarium, Biological Sciences, Ahmadu Bello University (A.B.U.) Zaria (1010).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Acute Toxicity Studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Lorke method (1983) was used for this study. Doses of 500, 1000, 2000, 3000, 4000 and 5000 Mg/Kg body weight (bw) and 8 mice were used. Doses of 10,000 and 11,000 Mg/Kg bw and 3 mice were used orally.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Chronic Toxicity Studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The use of Hymenocardia acida in traditional medicine is normally a long term administration and this is why the aim of this study is to monitor the long term effect of this drug on the animal tissue and organs. Male Swiss albino mice aged 4-6 weeks were used and these were grouped into 3 of 6 mice each. The control group (1) was given un-amended diet and water. Whereas the treated (2 & 3) groups were given amended diets of 25%w/w and 50%w/w of the plant root bark respectively for 3 months. The pre and post-treatment water-intake and body weights of each mouse were daily recorded. At the end of the 3 months, the mice were sacrificed and their various organ weights recorded. The organs checked for histopathology include the liver, the kidney, the heart, the lung and the skin. The organs were fixed in 10% buffered neutral formalin for 72h before processing. This was an attempt to maintain the tissues as it was in the ante- mortem before the post- mortem.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The different tissues were then labelled and allowed to dehydrate in graded series of alcohol in the ascending order of 70%, 80%, 95% and 100% alcohol after which the tissues were cleared with xylene and impregnated with paraffin wax, separately embedded for sectioning with rotatory microtome and microtome knife. The tissues were then sectioned at 6- micro thick and were mounted on a clean and grease free slip and then dried in an oven. The stained slides were examined with the compound microscope at X40 objectives and the results were recorded. This was repeated with the other 6 mice fed with 50% w/w amended diet and the control group (guided by the Department of Pharmacology, Ahmadu Bello University, Zaria). This experiment was repeated for female albino mice.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Haematology

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The experiment was aimed at evaluating the effects of the plant on blood parameters with the view of investigating the traditional claims of the plant by the Hausas in the treatment of sickle cell anaemia. The parameters observed were full blood count or differential count for complete blood count (CBC), packed cell volume (PCV), mean haemoglobin concentration (MHC), total red blood cell count (RBC count), mean corpuscular volume (MCV), total white blood cell count (WBC count), differential Leucocyte count (LC), and platelet count.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Swiss albino mice were fed with amended diet containing 25%w/w and 50%w/wof the root bark. After 65 days, the mice were euthanized and the blood parameters were evaluated using standard methods described by (Akinloye and Olorede, 2004). The results were compared with animals fed on unamended diet.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Acute toxicity studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The water extract of Hymenocardia acida when administered orally was found to be safe. No death was recorded nor was any sign of toxicity observed within 24h of administration even at a higher dose of 11,000mg/kg although LD50undefinedof values greater than 5,000mg/kg have no therapeutic value (Lorke, 1983).

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">P.N. Olotu et al: Continental J. Pharmaceutical Sciences 4: 35 - 39, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Chronic Toxicity Studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Over 90 days of the experimental studies, the mice fed with 25% w/w amended diet did not show any observable tissue damage in the lungs, hearts, kidneys, brain intestines and spleens. The control rats also showed no visible liver damage but the rats fed with 50% w/w amended diet reacted differently. They showed a focal area of hepatic necrosis and the globule cells of the intestine were covered with progressive mucin and lymphocyte proliferations were observed with the spleen. But obviously there was no tissue damage of the pancreas, hearts, lungs, kidneys and brain. This is to say that prolonged (chronic) treatment with this drug in traditional medicine should be cautioned.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Furthermore, the body weight, feed and water-intake increase with the mice fed with the lower concentration of the amended diet (25% w/w) but decreased with the higher concentration (50% w/w). There was also a prominent change with the post treated mice. This result may suggest the use of the plant for nutritional purposes at lower concentration. The different plates (1, 2, 3 and 4) are shown below.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Haematology studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Analysis of the blood parameters showed very significant increase with the RBC (Table 1) this justifies the claim of the plant in the treatment of anaemia. Analysis of the plant on the remaining blood parameters was not significant (Table 2, 3, 4, 5, 6 & 7).

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Plate 1: Fatty degeneration of the Hepatic cells        Plate 2:  Necrosis of the Hepatic cells

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Plate 3: Progressive mucin seen on the                Plate 4: The section of the spleen showing

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">            globule cells of the Intestine                                  lymphocyte proliferation

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">P.N. Olotu et al: Continental J. Pharmaceutical Sciences 4: 35 - 39, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 1: Red blood cells (RBC) Root bark

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 2: Packed cell volume (PCV) Root bark

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 3: Hb (Root bark)

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">Table 4: TP (Root bark)

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 5: White blood cells (WBC) Root bark

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">Table 6: Neutrophils (Neu) Root bark

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; line-height: normal;">Table 7: Lymphocytes (Lymp) Root bark

<p style="margin-bottom: 0.0001pt; line-height: normal;">ANOVA <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The toxicity and haematology studies of the root bark of Hymenocardia acida have been carried out successfully. The results obtained could serve as the tool for establishing the safety of the use of this plant in traditional medicine and in anaemia.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">P.N. Olotu et al: Continental J. Pharmaceutical Sciences 4: 35 - 39, 2010

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<p style="margin-bottom: 0.0001pt; line-height: normal;">REFERENCES'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Agishi, E. C., (2004). Etulo, Idoma, Igede, Tiv and Hausa names of Plants. AGITAB Publishers Ltd. Makurdi, Nigeria. pp.188.

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Akinloye, J., & Olorede, M. (2004). Toxicity study of the Leaves of ''Cochlospermum planchonii. ''Vol. 13. Pp 23.

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<p style="margin-bottom: 0.0001pt; line-height: normal;">Bouquet, A., & Debray, M. (1974): Medicinal plants of the Ivory Coast, ''Trav. Doc. Orst ''32: (Serv. Cent. Document Orstambondy 93140 France) pp.1

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<p style="margin-bottom: 0.0001pt; line-height: normal;"> Bouquet, A. (1969). Medicinal plants of the Ivory Coast, Trav. Doc. Orst pp 116''. ''

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Burkill, H. M., (1985). The Useful Plants of West Tropical Africa, 2nd Edition, Vol.1. Royal Botanic Gardens, Kew, 960p.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Daziel, J. M., (1937). Useful plants of Tropical West Africa. Crown Agent for Overseas Government and Administration, London. pp 52-53.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Kerharo, J. (1974). Historic and Ethnopharmacognosic review on the belief and Traditional practices in the treatment of sleeping sickness in West Africa, Bull Soc. Med. Afri. Noire Lang. FR. 19: (Fac. Med. & Pharm Dakar          Senegal) pp. 400.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Lorke, D.A. (1983). A New Approach to Practical Acute Toxicity Testing. Arch. Toxicology 54:275-287.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/09/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/10/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author:

<p style="margin-bottom: 0.0001pt; line-height: normal;">J.S Gushit

<p style="margin-bottom: 0.0001pt; line-height: normal;">Department of Science Laboratory Technology, Faculty of Natural Sciences University of Jos, Nigeria.

<p style="margin-bottom: 0.0001pt; line-height: normal;">Email: [mailto:*hajara40@yahoo.co.uk johngushit]@yahoo.com

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010                                           ISSN: 2141 - 4149

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">A SURVEY OF THE ACTIVITIES OF TRADITIONAL MEDICINE PRACTITIONERS (TMPS) IN SOUTHERN IJAW, SAGBAMA AND OGBIA LOCAL GOVERNMENT AREAS OF BAYELSA STATE, NIGERIA

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Department of Pharmacognosy and Herbal Medicine, Niger Delta University,Wilberforce Island, Nigeria

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<p style="margin: 0cm 17pt 0.0001pt; line-height: normal;">ABSTRACT

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">The impact of Traditional Medicine Practitioners (TMPs) in healthhcare delivery, their role in over exploitation of natural plant resources plants were studied in Southern Ijaw, Sagbama and Ogbia Local Government areas of Bayelsa State, Nigeria. A total of sixty-nine (69) TMPs were interviewed. Most of the TMPs were general practitioners, and bone setters. Patients are referred to them from hospitals, chemists and churches. The practice may be going into extinction as more than three quarters of the TMPs are between age range 41 – 80 with about 13 % between 31 and 40 and approximately 40 % have not trained anyone. About 70 % of the respondents depend on collection of plants from the wild for treating their patients, thereby posing a serious bioconservation problem on species of plants they exploit.

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<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">KEYWORDS: ‘‘traditional medicine practioners’’ (TMPs), ‘‘medicinal plants’’, ‘‘Niger Delta’’, ‘‘bioconservation’’.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Broad use of traditional medicine is often attributable to its accessibility and affordability in developing countries.(Mahonge et al., 2006; De Silva, 1997; Sofowora, 1993; Bodeker, 1994; Bhat et al. 1990). In Uganda for instance, the ratio of Traditional Medicine Practitioners (TMPs) to population is between 1:200 and 1:400. This contrasts with the availability of orthodox Practitioners for which the ratio is typically 1:20000 or less (WHO, 2002). Moreover the distribution of such personnel may be uneven, with most being found in cities or other urban areas and therefore difficult for rural populations to access. Traditional medicine is sometimes also the only affordable source of healthcare. Research has shown in places like Ghana, Kenya and Mali, that a course of pyrimethamine/suilfadoxine antimalarias can cost several dollars, yet per capital out-of-pocket health expenditure amounts to only about 6US dollars per year. Conversely herbal medicines for treating malaria are considerably cheaper and may sometimes even be paid for in kind and according to the wealth of clients (WHO, 2002). The present study was carried out to document the activities of the Traditional Medicine Practioners (TMP’s) in Southern Ijaw, Sagbama, and Ogbia Local Government Areas of Bayelsa state ,Nigeria.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Methodology

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">''Study Area ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Bayelsa state is located in the Niger Delta region of Nigeria, it is bounded on the west by Rivers State, on the east and south by the Atlantic ocean and on the north by Delta State (Fig 1). It is a multiethnic state comprising of many ethnic groups such as Kolokuma, Ekpetiama, Igbiran, Atissa and Biseni, others are Nembe, Ogbia and Ogboin. Southern Ijaw,Sagbama and Ogbia are three of the 8 Local Government Areas of Bayelsa State (Fig.2). Southern Ijaw has its headquarter in Oporoma in the north area at 4o48’17’’N6o4’44’’E. The area has a coastline of approximately 60 km on the Bright of Bonny. It has an area of 2,682 km2 and a population of 319,413 at the 2006 Census (Federal Republic of Nigeria, 2007). Sagbama, on the otherhand has its headquaters in sagbama town, part of the area lies within the Bayelsa National Forest, it has an area of 945 km2and a population of 187, 146 at the 2006 census (Ferderal Republic of Nigeria, 2007) while Ogbia has its headquarters in Ogbia town, the south part of the area at 4o39’00’’N 6o16’0oE. It has an area of 695 Km2 and a population of 179.926, the inhabitants and immigrants are mainly Ijaw people (Federal Republic of Nigeria, 2007).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure 1: Map of Nigeria showing Bayelsa

<p style="margin-bottom: 0.0001pt; line-height: normal;">State (Red - study area)

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo: Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The people are mainly peasant/subsistence farmers and fishers predominantly living in rural communities, which informed their dependence on Traditional Medicine Practitioners (TMPs) for their health care needs. For the purpose of this work, four communities were chosen in each of the local government areas. Agbere, Agoloma, Okunbiri and Ogobiri were selected at random in Sagbama while Amassoma, Ondewari, Opuama and Oporoma were selected in Southern Ijaw. Otuasega, Kolo, Oruma and Imirigi were selected in Ogbia. The Ijaw ethnic groups dominate these areas.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Figure 2: Map of Bayelsa State showing the Local government Areas

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The study population for this survey was Traditional medical practitioners (TMP). This is a preliminary study carried out in 2009. TMPs were identified and selected for this pilot stage. 23 TMPs were selected in each of the three selected local governments;  Southern Ijaw, Sagbama and Ogbia Local Government areas. The preliminary survey was carried out through the use of a structured and pre-tested interview schedule to elicit information on their demographic and socioeconomic data, role in the heaithcare system, clients, training received e.t.c. The questionnaire was designed in an open-ended format. Other instruments used were oral interview and observation. The questionnaire consisted of 25 questions and was of a self administrable type worded in simple language, however, the investigator had to fill in the questionnaire in an interview type form, since most of the TMPs were illiterate. The respondent’s consent was sought and obtained and the objective was clearly explained. A few of the plants used by the various TMPs were identified at site by their local names and collected. Herbarium specimens were deposited in herbarium of  the Department of Pharmacognosy and Herbal Medicine, Niger Delta University. Specimens were sent to the Forestry Research Institute of Nigeria, Ibadan, for identification by their scientific names.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS

<p style="margin-bottom: 0.0001pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table 1: Ages and Educational Background of the Traditional medicine Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table 2: Form of practice and Areas of specialization of the Traditional medicine Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo: Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Table 3: Training of the Traditional medicine Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table 4: Causes of illness/disease and Methods of Diagnosis by the Traditional medicine Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table 5: Treatment of Patients by Traditional Medicinal Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; line-height: normal;">Table 6: Source of medicinal plants and packaging materials of medicines by Traditional medicine Practitioners <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">More than three-quarter of respondents are in the age range 41 – 80 and only 13 % between 31 – 40 (Table 1). This shows that after the death of those within the main age range, there is likelihood of disappearance of traditional medicine practice in these regions. About half of respondent do not have a formal education while about 40 % had primary six certificates (Table 1). This, according to some of the respondents was as a result of the terrain of Niger Delta which made these communities far from orthodox forms of education, most of these areas were across waters during their (TMPs) early/formative years. Most of them had the knowledge and practice of traditional medicine transferred to them verbally and not written. The problem of education has now been overtaken as there are now schools and teachers are employed and posted to the rural areas. 35 % of respondent are medical herbalists while about 40 % combine at least two forms of practice, 10% are into massaging and less than 10 % are traditional birth attendants (Table 2). About 40 % are into general practice and 17 % are specialized in obstetrics and gynaecology, those in paediatrics are the smallest in number (Table 2).

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo: Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">More than three-quarters (80 %) are into full time practice (Table 2). Approximately three-quarters (79 %) of them were trained as TMPs through parental inheritance, while less than 20 % learnt by apprenticeship (Table 3). This indicates that indigenous knowledge about plants and their medicinal values are still kept in families and passed down from generation to generation. Nearly 40 % have not trained anyone while about the same percentage has trained only between 1 and 10 people (Table 3) since they started practice. Approximately 90% have not trained any of their biological children, only less than 10 % have trained between 1 and 3 of their children (Table 3) and this corroborates what has been earlier mentioned in Table 1, that the extinction of traditional medicine practice in this region could be imminent, if nothing is done to encourage their practice. This is as a result of modern education which has taken the full attention of their children and wards. Approximately 40 % were trained from birth and around the same percentage had between 1 to 10 years of training (Table 2). Causes of sicknesses were mainly attributed to either physical or biological (Table 4). Physical causes of sickness are also known to orthodox medicine in which sickness can be as a result of injurious elements entering the human system through food, drink, skin e.t.c. (Lambo, 1979, Sofowora, 2008). Psychological causes of sickness, although known to orthodox doctors, are not known to TMPs (Lambo, 1979) and this has been validated from the result as none of the respondents attributed cause to psychological problem (Table 4). Diagnostic method is majorly by biological examination as about half of the respondent (45.5 % ) said they do so biologically (Table 4). Although, they lack knowledge of the scientific system of medicine in the performance and interpretation of tests, the TMPs use their own sensory organs to carry out biological examinations e.g tasting urine, smelling sores for putrefaction and observing the colour of vomited food which sometimes indicates ingestion of poison (Sofowora, 2008). About half of these patients are outpatients, others are either treated in their homes or admitted (Table 5). Referral of patients from other TMPs, chemist shops, churches and hospitals is common among the respondents with other TMPs as the major (47 %) (Table 5). Almost three-quarters of respondents do not keep records of clients (Table 5) probably because of their level of literacy. Plant collection are majorly from wild, farms and gardens and from herbsellers (70 %) and this is done very early in the morning with the belief that the spirit of the plant is responsible for the potency, only about 30 % cultivate medicinal plants  (Table 6). Less than 10 % buy from herbsellers which is in contrast to TMPs who buy mostly from herbsellers in the South west (Omobuwajo et al., 2008). This poses a serious bioconservation problem on species of plants they exploit. It has been reported that wild populations of numerous species are over exploited around the globe and the demand created by traditional medicine is one of the causes of overexploitation and they are not immuned to the current environmental crisis in the world. Plastic bottles are the main packaging materials (53 %), use of leaves and animal horns are getting obsolete and this is a pointer to the fact that the TMPs are rising up to the challenge of hygiene (Table 6) .A list of the plants commonly used by the TMPs and found in the region are given in Appendix I.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Part of Sagbama lies in the Bayelsa National Forest and if the activities of the TMPs are not controlled, many species of plants will be endangered because the forest will be invaded,coupled with the activity of those felling commercial timber without replanting causing destruction of the herbs/lower plants. The other Local governments have major forests in them and Bayelas state is in the Niger Delta region considered one of the Hots spots of biodiversity in the world. There is no doubt that a proper record of Traditional medicine Practice in Bayelsa state as a whole is needed. The percentage of the populace who visit them is large. There is also the need to organize workshops for TMPs on conservation of natural resources, hygiene etc. to enhance their role in primary health care as they are a force to be reckoned with in healthcare. To deny they exist would do no good to the people; training them and equiping them would enhace their role. One of the modes of traditional medicine which is unique to the Ijaws is bone setting and this is next to those that are into general practice. It is a common knowledge that there are few types of broken bones which cannot be set by the bone setters in Ijaw land, some bone setters have referrals from some hospitals. There is an urgency to learn from their practice before the information is lost, as they are a major source of information on medicinal plants which are leads to new drugs.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">REFERENCES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Bhat, R.B., Etejere, E.O. and V.T. Oladipo (1990). Ethnobotanical studies from Central Nigeria, Econ. Bot., 44 (3): 382-390.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Bodeker, G. (1994). Traditional Health Knowledge and Public Policy. Nat Resour., 30 (2) 91-106.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo: Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">De Silva (1994). Industrial Utilization of medicinal plants in developing countries. In: Medicinal plants for forest conservation and healthcare, Non-wood forest product, Bodeker G., Bhat, K.K.S., Burkey, J. and P. Vantomme, (Eds.), No. 11 FAO Rome Italy

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Federal Republic of Nigeria (2007). 2006 Census, Official Gazette, No. 24 vol. 94. Publisher: Federal Government Printer, Lagos, Nigeria, FGP 71/52007/2,500 (DL24).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Lambo, J.O. (1979). The healing powers of herbs with special reference to obstetrics and gynaecology, African Medicinal plants. (ed. Sofowora, E.A) University of Ife Press, Ile-Ife Press, Ile-Ife, pg 23.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Mahonge, C.P.I., Nsenga, J. V., Mtangi and A.C. Matte (2006). Utilization of medicinal plants by Walguru people in east Uluguru mountains, Tanzania. Afr. J. Trad. CAM, 3 (4): 121-134

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Omobuwajo, O.R. Alade, G. and A. Sowemimo (2008). Indigenous Knowledge and practices of women herb sellers of Southwestern Nigeria. Indian Journal of Traditional Knowledge, Vol. 7(3) : 505-510

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Sofowora, A (2008). Medicinal Plants and Traditional Medicine in Africa. 3rd. Edition, Spectrum Books Limited, Ibadan, Nigeria, 37-43, 249-258

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">World Health Organization (2002). Traditional Medicine Strategy 2002 – 2005, pg 1.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/09/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/10/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author

<p style="margin-bottom: 0.0001pt; line-height: normal;">G.O. Alade

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Department of Pharmacognosy and Herbal Medicine, Niger Delta University, Wilberforce Island, Nigeria

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">G.O. Alade and O.R. Omobuwajo: Continental J. Pharmaceutical Sciences 4: 40 - 46, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Appendix 1: Plants commonly used by Traditional medicinal practitioners in Southern Ijaw, Sagbama and Ogbia Local Government Areas <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 47 - 50, 2010                                           ISSN: 2141 - 4149

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">PHYTOCHEMICAL SCREENING OF THREE MEDICINAL PLANTS NEEM LEAF (Azadirachta indica), HIBISCUS LEAF (Hibiscus rosasinensis) AND SPEAR GRASS LEAF (Imperata cylindrical)

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<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: 36pt; line-height: normal;">K. E. Ayeni and Yahaya S,A

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: 36pt; line-height: normal;">Science Technology Department Federal Polytechnic, P.M.B 420, Offa.

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<p style="margin-bottom: 0.0001pt; text-indent: 36pt; line-height: normal;">ABSTRACT

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; line-height: normal;">This research work determined the bioactive constituents of some medicinal plants and their effectiveness in the area of pharmacology or pharmaceutical. The phytochemical screening carried on the leaves extract of A. indica, H. rosasinensis, I. cylindrical revealed the presence of some active ingredients such as Alkaloids, Tannins, Saponins, and Phenols also glycosides, steroids, terpenoids, flavonoids and phlobatanins are present in this extract. The result demonstrated that the presence of phytochemical components in the leaves extract. It was observed that Alkanoids has the following values, 0.52g in A. Indica, 0.51g in H. Rosasinensis, 0.42g in I. cylindrical, while Tannins also has the following value 9.00g in A. indica, 8.40g in H. Rosasinensis, 9.20g in I. Cylindrical. Saponins has the value of 1.99 in A. indica, 1.80 in H. rosasinensis, 1.30 in I. cylindrica. Flavonoids have the value of 0.62 in A. indica, 0.38 in H. rosasinensis, 0.32 in I cylindrica. Phenol has the values of 0.024 in A. Indica, 0.600 in H. rosasinensis, .050 in I. cylindrica.

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<p style="margin-bottom: 0.0001pt; text-align: justify; text-indent: 36pt; line-height: normal;">KEYWORDS: Alkaloid, glycoside, flavonoid, Tannins

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">INTRODUCTION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">From the inception of the existence of earth, plant has been of great importance to the animal kingdom. It contributes either as a source of food or shelter. In the primitive ages, plants were also used for clothing therefore provides the basic needs of humans and animals as well. Out of these plants medicinal plants are common and are source of much attention in Africa. (Akenova, et al., 1996).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Uniformity of the quality of drug is also of great importance as far as the therapeutically active constituent of raw material is concern.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This makes it possible for pharmacist to prescribe Numerical values through which commodities are assessed and are used to ensure uniformity of standards.(Amen, 1996)

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Medical plant (Akinmoladun, et al., 2007) is defined as one, which contains substance that can be used for therapeutic purposes and its precursor for the synthesis of useful drugs. They contain nutrients that can heal the body (Frease and Evans, 1985).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Material like these plants that has cellular structure is referred to as organized drug in pharmacy and those with non-cellular structure as unorganized or a cellular drug (Akinpelu, et al., 2006).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Medicinal plants are termed as crude drugs of natural or biological origin by pharmacists to describe whole plant or plant parts having medicinal properties (Okwu et al., 2006).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">COLLECTION AND PREPARATION OF PLANT SAMPLES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The plant materials were brought from the school compound in Federal Polytechnic Offa, Kwara State. The plants were processed and analyzed.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PROCESSING OF PLANT SAMPLES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The leaves of the plant are properly washed in tap water and the rinsed in distilled water. The rinsed leaves are dried in an oven at a temperature of 35 – 400C for 3 days. The dried leaves of each plant are pulverized using a mortar and pestle, to obtain a powdered form. The powdered form of these plants is stored in airtight glass containers, protected from sunlight until required for analysis.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PREPARATION OF AQUEOUS EXTRACT OF PLANT SAMPLES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The aqueous extract of each plant sample is prepared by soaking 10g of powdered sample in 200 ml of distilled water for 12 h. The extracts are then filtered using filter paper. The extracts are then concentrated to ¼ of the original extracts i.e. 50 ml.

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: 36pt; line-height: normal;">K. E. Ayeni and Yahaya S,A: Continental J. Pharmaceutical Sciences 4: 47 - 50, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PREPARATION OF ETHANOL EXTRACT OF PLANT SAMPLES

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The ethanol extract of each plant was prepared by soaking 10g of powdered samples in 100ml of ethanol for the same 12 h. The extracts are then filtered using filter paper. The extracts are then concentrated to 50ml of the extracts sample and stored in airtight container.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">PHYTOCHEMICAL SCREENING METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A portion of the concentrated extract was used for the screening tests, both qualitative analysis and quantitative analysis using standard method (Edcoga et al., 2005).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">QUALITATIVE ANALYSIS ON PHYTOCHEMICAL CONSTITUENTS

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(a)                0.5g of powdered sample of each plant is boiled in 20ml of distilled water in a test tube and filtered 0.1% FeCl3 is added to the filtered samples and observed for brownish green or a blue black colouration which shows the presence of TANNINS.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(b)                Phlobatannins:  10ml of aqueous extract of each plant sample is boiled with 1% HCl acid in a test tube or conical flask. If the sample of plant carried phlobatannins, a deposition of a red precipitate will occur and indicates the presence of phlobatannins.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(c)                Saponins:  2g of powdered sample of each plant is boiled together with 20ml of distilled water in a water bath and filtered. 10ml of the filtered sample is mixed with 5ml of distilled water in a test tube and shaken vigorously to obtain a stable persistent froth. The frothing is then mixed with 3 drops of olive oil and for the formation of emulsion which indicates the presence of saponins.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(d)                Flavonoids:  A few chop of 1% NH3 solution is added to the aqueous extract of each plant sample in a test tube. A yellow coloration is observed if flavonold compound are present.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(e)                Terpenoids:  5ml of aqueous extract of each plant sample is mixed with 2ml of CHCl3 in a test tube 3ml of concentrated H2SO4 is carefully added to the mixture to form a layer. An interface with a reddish brown coloration is formed if terpenoid constituent is present.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(f)                 Glycosides:  1ml of concentrated H2SO4is prepared in test tube 5 ml of aqueous extract from each plant sample is mixed with 2ml of glacial CH3CO2H containing 1 drop of FeCl3. The above mixture is carefully added to 1ml of concentrated H2SO4 so that the concentrated H2SO4 is underneath the mixture. If cardiac glycoside is present in the sample, a brown ring will appear indicating the presence of the cardiac glycoside constituent.

<p style="margin: 0cm 0cm 0.0001pt 54pt; text-align: justify; text-indent: -36pt; line-height: normal;">(g)                Alkaloids:  5g o f the plant sample is prepared in a beaker and 200ml of 10% CH3CO2H in C2H5OH is added to the plant sample.

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">The mixture is covered and allowed to stand for 4 hours. The mixture is then filtered and the extract is allowed to become concentrated in a water bath until it reaches ¼ of the original volume. Concentrated NH4OH is added until the precipitation is complete. The whole solution is allowed to settle and the precipitate is collected and washed with dilute NH4OH and the filtered. The residue is alkaloid which is then dried and weighed.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">QUANTITATIVE ANALYSIS OF PHYTOCHEMICAL CONSTITUENT

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; text-indent: -23.25pt; line-height: normal;">a)         Phenols:  The quantity of phenols is determined using the spectrophotometer method.  The plant sample is boiled with 50ml of (CH3CH2)2O for 15 minutes.  5mml of the boiled samples is then pipette into 50ml flask and 10ml of distilled water is added. After the addition of distilled water 2ml of NH4OH solution and 5ml of concentrated CH3 (CH2)3 – CH2OH is added to the mixture.  The sample is made up to mark and left for 30 minutes to react for colour development and measured at 505nm wavelength using a spectrophotometer.

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; text-indent: -23.25pt; line-height: normal;">b)         Tannins:  Quantity of tannins is determined by using the spectrophotometer method.  0.5g of plant sample is weighed into 50ml plastic bottle 50ml of distilled is added and stirred for 1h.  the sample is filtered into a 50ml volumentric flask and made up to mark 5ml of the filtered sample is then pipetted out into test-tube and  mixed with 2ml of 0.1m FeCl3 in 0.1m HCl and 0.008m K4Fe (CN)63H2O.  The absorbance is measured with a spectrophotometer at 395nm wavelength within 10min.

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; text-indent: -23.25pt; line-height: normal;">c)          Saponins:  The sample were ground and 20g of each plant sample is put into a conical flask and 100ml of 20% C2H5OH is added to the plant sample.  The sample is heated over a hot water bath for 4 hours with continuous stirring at about 550C.  The mixture is then filtered and the residue re-extracted

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: 36pt; line-height: normal;">K. E. Ayeni and Yahaya S,A: Continental J. Pharmaceutical Sciences 4: 47 - 50, 2010

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; text-indent: -23.25pt; line-height: normal;">d)         with another 200ml of 20% C2H50H.  Then the combined extracts are reduced to 40ml over a water bath at about 900C.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The concentrated is then transferred into a 250mlseparation funnel and 20ml of (CH3CH2)2O is added to the extract and shaken vigorously. The aqueous is recovered while the (CH3CH2)20 layer is discarded and the purification process is repeated 60ml of N-C4H9OH is added and combined n-C4H9OH extracts is washed twice with 10ml of 5% NaCl. The remaining solution is then heated in a water bath and after evaporation: the samples are dried in the oven to a constant weight.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 41.25pt; text-align: justify; text-indent: -23.25pt; line-height: normal;">e)          Flavonoids:  10g of plant sample is repeatedly extracted with 100ml of 80% aqueous methanol at room temperature.  The whole solution is then filtered through filter paper and the filtrate is later on transferred into a water bath and solution is evaporated into dryness.  The sample is then weighed until a constant weight.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Table 1 is the results on the quantitative analysis of phytochemical constituents of three medicinal plants. <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">+ = The presence of phytochemical constituents, - =The absence of phytochemical constituents:-

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Table two: QUANTITATIVE ANALYSIS OF PHYTOCHEMICAL CONSTITUENT (%) <p style="margin-bottom: 0.0001pt; line-height: normal;">

<p style="margin-bottom: 0.0001pt; line-height: normal;">DISCUSSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">For the qualitative analysis results, below is the discussion. The research work that was carried out on the three medicinal plants shows that phytochemical constituents are present in which it was summarized in Table 1.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">It shows that tannins, saponins, flavonoids, terpenoid and alkaloid, phenol were present in all the three plants. But phlobatannins were found to be absent in the three plants. Cardiac glycosides were present in A. indica  and I. cylindrica and found to be absent in H. rosasinensis.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">QUANTITATIVE ANALYSIS OF PHYTOCHEMICAL CONSTITUENTS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The above results show in the table reveal the five (5) major groups phytochemicals constituents  the medicinal plantsre shown in the Table 2.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A. indica and H. rosasinensis have the highest yield of alkaloid which is 0.5g in which I. Cylindrica has the lower yield of alkaloid which is 0.4g. But A. Indica and I. cylindrica showed from the result to have highest yield of Tannins which is 9.00g. Moreover A. indica, H. rosasinensis, and T. cylindrica have been founded to have similar yielded of saponins which are 1.99, 1.80 and 1.30 percentages respectively.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: center; text-indent: 36pt; line-height: normal;">K. E. Ayeni and Yahaya S,A: Continental J. Pharmaceutical Sciences 4: 47 - 50, 2010

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">'' ''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">A. indica has the highest yield of flavonoids which is 0.62% followed by H. rosasinensis which is 0.38% and I. cylindrica is found to have the least amount of flavonoid which is 0.32%.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Finally H. rosasnensis has the highest yield of phenols quantity and followed by A. indica and I. cylindrica which are in similar or the same range.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">This research work has revealed further potentials of these three plants in the area of pharmacology as potential source of useful drugs. T his study therefore has provided some biochemical basis for ethno pharmacological uses of these plants in the treatment and prevention of various diseases and disorders.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RECOMMENDATION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Since the results of the phytochemical screening have shown that the extract of the three samples contain alkaloids, tannin, saponin, phlobatannin, terpenoid, flavonoid, cardiac glycoside and phenol.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Therefore I recommend that these extracts should be used in the production of drugs in the area of pharmaceutical or pharmacology for the treatment of intestinal track, diarrhea, headache, skin disease and it should be used as a source of pesticide and insecticide, also herbicide in the agricultural area so as to improve the yield of crops and reduce pests, weeds and other organism which are competing with man.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">REFERENCES

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Akinpelu, D. A. and Onakoya, T.M. (2006). Antimicrobial activities of medicinal plant used in folk lore

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">remedies in south-western. Afri. J. Biotechnol, 5:1078-1081.

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Akinmoladun A. C., Ibukun E.O., Afor E., Obuotor, E.M. and Farombi E.O. (2007). Phytochemical constituent

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">and antioxidant activity of extract from the leaves of Ocimum gratissimum. Sciences Research Essay 2: 163

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">166.

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Okwu, D. E. and Josiah, C. (2006), Evaluation of the chemical composition of two Nigerian Medicinal plants

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">''Afri. J. Biotechnol.'' 5(4): 357-361.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Oluronke, Taiwo Department of Applied Oral Science, Faculty of Denstistry, Dalhousie, University, Canada

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">B3H315. A research article on antibacterial activities of extracts from Nigeria medicinal plants.

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Akenova, M.E. and Attackrah, A.N. (1986) Control of spear grass (imperata cylindrical {L} Bearuv in an alley

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">cropping fallow. Nitrogen –fixing Tree research reports 4; 24-28.

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">Amon, (1996) Imperats management for small holder an extensionists guide to rational imperata management

<p style="margin: 0cm 0cm 0.0001pt 63pt; text-align: justify; text-indent: -63pt; line-height: normal;">for small holders.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">''' '''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/09/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/10/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author

<p style="margin-bottom: 0.0001pt; line-height: normal;">K. E. Ayeni

<p style="text-align: justify; line-height: 150%;">Science Technology Department Federal Polytechnic, P.M.B 420, Offa''' '''

<p style="text-align: justify; line-height: 150%;">

<p style="text-align: justify; line-height: 150%;">''' '''

<p style="text-align: justify; line-height: 150%;">  ''' '''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010                                           ISSN: 2141 - 4149

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">© Wilolud Journals, 2010                                                                                 http://www.wiloludjournal.com

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: 150%;">''' '''

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Tableting properties of acid modified cassava starch dehydrated in alcohol

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M.1, Oyi, A.R2 and Isah, A.B2

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">1Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria, 2Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">ABSTRACT

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">The work was aimed to investigate the suitability of acid modified cassava starch (ACS) dehydrated in ethanol for use as filler/binder in direct compression. ACS was obtained by acid hydrolysis using hydrochloric acid at both 6.0 N and 8.0 N for 24 and 18 respectively. Powders retained on 150 µm sieve were used in tablet formulation. Tablets were made using metronidazole (200mg) in a ratio 1:1 using the direct compression method. The results obtained showed that there was a significant increase in dissolution rate, crushing and tensile strength with reduced friability of ACS as compared to their native form. Generally, ACS showed increase dissolution rate profile and lower disintegration time as compared to microcrystalline cellulose which showed a superior crushing and tensile strength.

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 17pt 0.0001pt; text-align: justify; line-height: normal;">KEYWORDS: cassava starch, microcrystalline cellulose, acid hydrolysis, metronidazole, filler/binder.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Introduction

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Cassava starch has many remarkable characteristics including high paste viscosity, high paste clarity and high freeze-thaw stability, in particular, the native starch with high purity can be readily modified by physical, chemical and enzymatic process to many diversified products to improve the starch functionality and consequently, encourage more industrial application. The simplest and most common starch modification is by acid hydrolysis which is widely used in food, paper, textile and pharmaceutical industries (Karntarat et al, 2008). Acid modification changes the physicochemical properties of starch without destroying its granular structure (Singh and Ali, 2000). It has been established that acid modified starch obtains improved properties as Tableting excipient if the starch product obtained is first dehydrated by means of a water-miscible organic solvent and the resulting starch product dried. The thus obtained starch powder has an increased specific surface area and, with respect to binding force and breaking strength, have improved properties as Tableting excipients (Buwalda and Willemina, 1997).

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Acid treatment can cause a breakdown of the polymeric structure in cassava powder to obtain a less elastic but a more plastic material which is amenable to direct compression (Florence and Roland, 2002). Recent advances in formulation technologies have lead to a shift from traditional wet granulation to direct compression manufacturing process in the development of solid oral dosage forms due largely to process expedition, easy handling, and time and cost savings (Nyström and Glazer, 1985). Tableting excipients are classified according to their functional properties such as binder, fillers, disintegrants, lubricants, flavors and coloring agents. Suitable starch products may also perform several functions, such as the combination of filler and binder (often designated as filler/binder). In this study, acid modified cassava starch dehydrated in alcohol was evaluated for its suitability as a filler/binder in direct compression and subsequently compared with native cassava starch and microcrystalline cellulose (Avicel PH 101).

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">MATERIALS AND METHODS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Materials

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ethanol 96% (BDH Chemicals Ltd, Poole England), concentrated hydrochloric acid and sodium hydroxide (May and Baker Laboratory Chemical, Dagenham, England), metronidazole powder (Vingesh International Limited, India), microcrystalline cellulose PH 101 (ATOZ Pharmaceuticals Limited, Ambaltur, India)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt -18pt; text-align: justify; line-height: normal;">       Production of acid modified starch

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Production of acid modified cassava starch was carried out as described by Buwalda and Willemina (1997). 450 grams of an aqueous suspension of starch (36% w/v wt starch) was poured into a stainless steel vessel. To this suspension, 28ml, 6N and 8N HCL was added drop-wise with stirring. Subsequently the reaction was conducted for 18 and 24 hours respectively at 50oC. After cooling, the modified starch product was separated from the reaction medium by filtration. On the filtrate, the separated starch product was washed 1:1 with water, then the starch product was suspended again in 250ml water and brought to pHundefined6 with sodium hydroxide solution. The

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">starch product was separated by means of filtration with 750ml water. A sample of 100g of the wet starch product separated by filtration was suspended in 800ml ethanol and stirred for 30 minutes. Subsequently, the starch product was separated by filtration and dried in Gallenkamp hot air oven (Philips Harris Ltd, England) at 40oC. The dried starch was ground to fine powder and those fraction retained on 150mm sieve were used for further studies.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt -18pt; text-align: justify; line-height: normal;">      Preparation of tablets

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">An Erweka tableting press (Erweka apparatebau GmbH, Germany) fitted with a 10.0 mm punch tip diameter was used. Metronidazole tablets were formulated using the direct compression method at a ratio 1:1 with cassava starch, acid modified starches and microcrystalline cellulose (MCC PH101) as excipients with 0.5 % magnesium stearate as lubricant at a pressure setting of 9 metric tones using the following formula

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">Table 1: Formula for metronidazole tablets <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> KEY

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CS = cassava starch, ACS6 = acid modified cassava starch using 6N HCl for 24 hrs, ACS8 = acid modified v cassava starch using 8N HCl for 18 hrs

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">EVALUATION OF TABLETS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Uniformity of weight

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ten tablets were weighed individually and collectively from each batch using Metler P163 balance (Zurich, Switzerland) and the mean weights computed. The percent coefficient of tablet weight variation (% CV) was calculated according to the formula (Bolhuis, 1988)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">% CV = standard deviation/mean weight……………. (1).

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Density of tablets

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Densities of tablets at corresponding pressure loads were used to evaluate compressibility. Tablet density was obtained from the weight of compact and its volume as follows:

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Relative density (g/ml) = weight of tablet (g) / tablet volume (ml)………. (2)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The volume of tablet was calculated from the relationship:

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">   Volume of tablet = Pr2tρ ……………….. (3)

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Where  r = radius of tablet, and

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">        t = tablet thickness

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">        ρ = particle density of the granules

<p style="margin: 0cm 0cm 0.0001pt 18pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Crushing strength

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The Monsanto hardness tester was used to determine the crushing strength of five tablets from each batch twenty-four hours to allow enough time for elastic recovery to occur after the tablets had been compressed.

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Tensile strength

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The radial tensile strength Ts of tablets was calculated from the equation:

<p style="margin: 0cm 0cm 0.0001pt 15pt; text-align: justify; line-height: normal;">

<p style="margin: 0cm 0cm 0.0001pt 15pt; text-align: justify; line-height: normal;">Ts = 2F / Πdt ……………………….. (4)

<p style="margin: 0cm 0cm 0.0001pt 15.1pt; text-align: justify; line-height: normal;">Where,    F = load needed to break the tablet,

<p style="margin: 0cm 0cm 0.0001pt 15.1pt; text-align: justify; line-height: normal;">               d = diameter of tablets

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">                     t = tablet thickness

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Friability test

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Ten tablets were dusted, weighed together and subjected to abrasion test in the Erweka TA3R friabilator (Erweka apparatebau GmbH, Germany) operated at 25 rpm for 4 minutes. The tablets were then dusted properly and weighed again collectively. The difference in weight was then determined and expressed as percentage friability value.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Disintegration time studies

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">The disintegration time of tablets was determined with Erweka disintegration apparatus (ZT3), (Erweka apparatebau GmbH, Germany) using the BP (2004) method. Water thermostatically maintained at 37o± 0.5oC was the medium. The time taken for all of the six tablets, one placed in each of the six tubes of the apparatus to disintegrate and pass through the mesh was recorded using a stop clock.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Dissolution tests

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Erweka disintegration apparatus ZT3 (Erweka apparatebau GmbH, Germany) was utilized using the basket method. One tablet was placed in the dry basket and lowered into the dissolution medium (0.1 N HCl) half way before the rotation began at a speed of 100 rpm. 10 ml of the sample was withdrawn from half way between the surface of the dissolution medium and the top of the rotating basket at 10 minutes interval for one hour. After every withdrawal, 10 ml of the medium was replaced. A one in ten dilution with the dissolution media was made before the absorbance of the sample was taken at 277 nm with Genesys 20 spectrophotometer (Madison, Wisconsin, USA).

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Statistical analysis

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Statistical analysis was done to compare the crushing and tensile strength of the formulation between MCC PH101, cassava starch and acid modified starches using the t-test. At 95% confidence interval, ρ value lower or equal to 0.05 was considered the limit of significance.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">RESULTS AND DISCUSSIONS

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Wight uniformity of metronidazole tablets can be attributed to the flow characteristics of the excipients with MCC PH101 known to have a poor flow properties as compared to acid modified cassava starch (Achor et al, 2010). The density of the tablets also reflects the densities of the excipients as reported by Achor et al (2010). The results of friability test for metronidazole tablets as shown in Table 2 shows that MCC PH 101 had better friability value (F4) as compared to cassava starch and its modified products (F1,F2 and F3). This can be attributed to the crushing strength of the tablets. Disintegration of tablets can be considered as the result of two processes; water uptake and the separation of the particles due to elastic expansion of the compressed particles and annihilation of the interparticulate hydrogen bonds followed by penetration of water between the particles (Michael, 2006). The more compact a tablet is, the less the porosity and hence less penetration of water into the tablet and as a result, longer disintegration time. All starch types for metronidazole tablets passed the BP (2004) specification for disintegration of uncoated tablets (within 15 min) except MCC PH 101. This can be attributed to the stronger bonds coupled with the impairment of swelling ability by better compressibility of MCC PH 101. This retards water penetration and cause tablet rupture less readily.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Table 2: Properties of metronidazole tablets

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> <p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">*value is mean and standard deviation is in parenthesis, number of replicate = 3

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">KEY: F1, F2, F3 and F4 represents metronidazole tablets formulated using CS, ACS6, ACS8 and MCC PH101 respectively as excipients.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Metronidazole tablets formulated using acid modified cassava starch showed tablets with higher crushing and tensile strengths as compared to its native from (Fig. 1) The crushing strength of a tablet, like its thickness, is a function of the die fill and compression force. In an ideal situation, at a constant die fill, the crushing strength values increase and thickness decreases as additional compression force is applied. Metronidazole tablets

<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">formulated using MCC PH 101 gave tablets with better crushing strength as compared to cassava starch. There was a statistical significant difference at P< 0.05 between MCC PH 101 and modified cassava starch. Also, between both batches of modified cassava starch, there was no statistical significant difference at P< 0.05.

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<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">Fig. 1: Crushing and tensile strength of metronidazole tablets

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;"> Fig. 2 shows the dissolution profiles of metronidazole tablets. The t50% (time taken for 50 % of the drug to be released) and t90% (time taken for 90 % of the drug to be released) were below 25 minutes except for tablet formulated using MCC PH 101 (F4). This can be attributed to its crushing strength. For metronidazole tablets, F1, F2 and F3 passed the BP (2004) specification for dissolution profile for uncoated tablet which states that 75 % of the drug should be released within 45 minutes. The monitoring of tablets crushing strength is especially important for drug products that possess real or potential bioavailability problems or that are sensitive to altered dissolution release profiles as a function of the compressive force employed.

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<p style="margin: 0cm 0cm 0.0001pt 36pt; text-align: justify; text-indent: 36pt; line-height: normal;">Fig. 2: Dissolution profile of metronidazole tablets

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">CONCLUSION

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">It can be seen that metronidazole tablets formulated with acid modified cassava starch showed improved tableting properties as compared to its native starch. MCC PH101 showed better friability, crushing and tensile strength as compared to cassava starch and its modified products, but in terms of its disintegration and dissolution profile, if attainment of high peak blood levels for the drug is a product objective, obtaining rapid drug dissolution from the tablet as seen with the modified cassava starch will be critically important.

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<p style="margin-bottom: 0.0001pt; text-align: center; line-height: normal;">Achor, M et al.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">REFERENCES

<p style="margin-left: 0cm;">Achor, M., Oyi, A.R. and Isah, A. B. (2010). Some physical characteristics of microcrystalline starch obtained from maize and cassava. Continental J. Pharmaceutical Sciences 4: 11-17.

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<p style="margin-left: 0cm;">Bolhuis, G.K. (1988). ''Mfg. Chem''., June, 29-36 (cited from: Garr, J.S.M. (1992). Compaction characteristics of direct compression tableting excipients. PhD thesis submitted to John Moore’s University, Liverpool).

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<p style="margin-left: 0cm;">Buwalda, P.L. and Willemina, A.A. (1997). U. S. Patent WO/1997/031627.

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<p style="margin-left: 0cm;">British Pharmacopoeia (2004). HMSO, London.

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<p style="margin-left: 0cm;">Florence, E. E. and Roland, S. O. (2002). Effect of acid treatment on the consolidation and plasto-elasticity of tapioca powder. Tropical Journal of Pharmaceutical Research, 1 (1):45-49

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<p style="margin-left: 0cm;">Karntarat, W., Sujin, S., Wannapong, T. and Darapond, T. (2008). Amylose/Amylopectin simple determination in acid hydrolyzed tapioca starch. ''J. Chil. Chem. Soc'', 53 (3):1565-1567

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<p style="margin-left: 0cm;">Michael, L. (2006). A cellulose based product and its interaction with water; Ph.D (Pharmaceutics) thesis work, Institute of Pharmaceutical Technology, University of Basel, Switzerland. pp 91

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<p style="margin-left: 0cm;">Nyström, C. and Glazer, M. (1985). Studies on direct compression of tablets. XIII. The effect of some dry binders on the tablet strength of compounds with different fragmentation propensity. Int J Pharm. 23:255-263.

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<p style="margin-left: 0cm;">Singh, V. and Ali, S.Z. (2000). Acid degradation of starch, the effect of acid and starch type. ''Carbohyr. Polym'', 41: 191-195.

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Received for Publication: 07/10/2010

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Accepted for Publication: 19/12/2010

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<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Corresponding Author

<p style="margin-bottom: 0.0001pt; line-height: normal;">Achor, M

<p style="margin-bottom: 0.0001pt; text-align: justify; line-height: normal;">Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria

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