SURFACE ACTIVITY AND RELEASE PROPERTIES OF SOME TROPICAL GUMS IN ARTEMETHER AND ARTESUNATE SODIUM TABLET FORMULATIONS
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- NGN 5000
ABSTRACT
Plant gums are natural polymers with low toxicity, high biodegradability and high compatibility with drugs making them useful as pharmaceutical excipients in solid, semi-solid and liquid formulations. This work was aimed at evaluating the surface activity and release properties of some tropical gums in artemether and artesunate sodium tablet formulations. Cashew gum (CSG) was extracted from stem bark exudates of Anacardium occidentale L., khaya gum (KYG) was extracted from stem bark exudates of Khaya senegalensis, afzelia gum (AFG) was extracted from seeds of Afzelia africana while prosopis gum (PRG) was extracted from seeds of Prosopis africana. Acacia gum B.P (ACG) and sodium carboxymethylcellulose (SCMC) were used as standards. The gums were evaluated for their physical, chemical and thermal properties. The surface activity was studied by determining surface tension at low concentrations (0.1 to 1.0 % w/v) of gum dispersions and by determination of critical micelle concentration in respect of each gum. The hydrophile-lipophile-balance (HLB) values of the gums were also determined. Cashew gum and prosopis gum were evaluated for their release properties. Artemether and artesunate sodium tablets containing varying concentrations of the gums (1.0 – 4.0 % w /w) and those containing 3 % w /w of ACG were formulated. Tablets containing 2 % w /w of gum with 2 or 4 % w /w chitosan as permeation enhancer were also formulated. The effect of the gums on the release and permeation of artemether and artesunate sodium in the presence of simulated gastric fluid and simulated intestinal fluid was determined using pig intestine as biological membrane. The yields of the gums from the different sources were: CSG (48.0% w/w), KYG (25.0% w/w), AFG (17.0% w/w) and PRG (18.2% w/w). The Hausner‟s ratio of the gums showed ranking of flow as ACG > KYG > CSG > AFG = PRG > SCMC. The viii polymers showed comparable and moderate surface activity but different critical micelle concentrations in the order SCMC < PRG = AFG = ACG < CSG < KYG. The solubility of the gums in water was in the order CSG > ACG > KYG > SCMC > AFG > PRG. Solubility of AFG, PRG and SCMC increased significantly in 1 % w /v solution of sodium hydroxide. The hydration and swelling capacities followed the same trend of SCMC > PRG > AFG > KYG > CSG > ACG. Cashew gum, khaya gum and acacia gum had significantly lower partition coefficient and higher HLB values while afzelia and prosopis gums had significantly higher partition coefficient and lower HLB values. Compatibility studies of CSG and PRG with artemether and artesunate sodium revealed that no new compound was formed. Artemether and artesunate sodium tablets containing cashew gum were characterized by lower crushing strength, lower friability and better release properties compared to those containing corresponding concentrations of prosopis gum. Prosopis gum showed better permeation enhancing effect on both artemether and artesunate sodium; but high concentrations of the gum were associated with poor release. Cashew gum, which is characterized by higher HLB value, can be used as a binder over a relatively wide range of concentrations to achieve a good drug release though with minimal permeation enhancement. Prosopis gum, which is characterized by lower HLB value, is capable of exerting good permeation enhancing effect on both water-soluble and poorly water-soluble drugs but must be used at low concentrations. Therefore, the suitability of gums as binders for ensuring good drug release and good permeation depends on the surface activity of the gum and the inherent properties of the drug to be formulated.
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