RESUMO
INTRODUCTION: Incorporation of pH modifier has been the usual strategy employed to enhance the dissolution of weakly basic drug from floating microspheres. Microspheres prepared using a combination of both ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) which shows highest release were utilize to investigate the effect of fumaric acid (FA), citric acid (CA), ascorbic acid (AA) and tartaric acid (TA) (all 5-20% w/w) incorporation on metoprolol succinate (MS) release. MATERIALS AND METHODS: EC, HPMC alone or in combination were used to prepare microspheres that floated in simulated gastric fluid and evaluated for a percent yield, drug entrapment, percent buoyancy and drug release. The higher drug release in combination (MS:HPMC:EC, 1:1:2) was selected for the evaluation of influence of pH modifiers on MS release. CA (5-20% w/w), AA (5-20% w/w), FA (5-20% w/w) and TA (5-20% w/w) were added and evaluated for drug release. Present investigation is directed to develop floating drug delivery system of MS by solvent evaporation technique. RESULTS: The microspheres of MS:HPMC:EC (1:1:2) exhibited the highest entrapment (74.36 ± 2.18). The best percentage yield was obtained at MS:HPMC (1:1) (83.96 ± 1.50) and combination of MS:HPMC:EC (1:1:2) (79.23 ± 1.63). CONCLUSION: MS release from the prepared microspheres was influenced by changing MS-polymer, MS-polymer-polymer ratio and pH modifier. Although significant increment in MS release was observed with CA (20% w/w), TA (20% w/w) and AA (20% w/w), addition of 20% w/w FA demonstrated more pronounced and significant increase in drug entrapment as well as release from MS:HPMC:EC (1:1:2) buoyant microspheres.
RESUMO
The present work deals with the formulation and evaluation of polymer-coated polysaccharide tablets of azathioprine prepared by direct compression method using different ratios of avicel (MCC), inulin and triacetin. The tablets formulations containing 25 mg of azathioprine were prepared and evaluated for thickness, hardness, friability, weight variation, content uniformity and in vitro dissolution test. Hardness and percentage friability were in the range of 7.23-7.43 kg/cm(2) and 0.21-0.41%, respectively, and showed 99-100% uniformity in drug content. The coated tablets exploiting different polymer combinations were evaluated for drug release under different pH conditions. The formulation containing Eudragit-S, Eudragit-L and cellulose acetate phthalate (ES, EL and CAP) (1:1:1) displayed desired release pattern with only 9.75% drug release in first 5 h (lag phase) and satisfactory release in lowered pH conditions. Drug release increased with the plasticizer (triacetin) concentration. Increase in the concentration of inulin and citric acid above 5% w/w increases the drug release. The addition of inulin in the formulation with coating level 28% w/w demonstrated increased drug release in presence of rat cecal content. Thus inulin containing ES, EL and CAP (1:1:1) polymer-coated formulation system can be used for the targeted delivery of azathioprine with desired release pattern.
