A Novel Approach to Extended Release Clopidogrel: Differentially Coated Mini-Tablets Filled In Hard Gelatin Capsules

Abstract

The main objective of the present study is to formulate an extended release formulation of clopidogrel bisulphate into mini-tablets coated with a combination of pH dependent polymer, pH independent polymer and pore former. Clopidogrel is extensively absorbed and 50% of drug is eliminated in urine in unchanged form. To improve the bioavailability of clopidogrel, the extended release formulation was formulated with an in-situ solubility enhancer, and barrier coated with moisture protective layer. The barrier coated minitablets are coated with the combination of pH dependant polymer (Hypromellose phthalate HP 50), pH independent polymer (Ethyl cellulose 7cps) and pore former (Hypromellose 5cps) at different ratio, with a weight build up of 10%w/w. In-vitro dissolution was studied in pH 1.2 HCl for 1 hour, followed by pH 6.5 phosphate buffer for 11 hrs, using USP dissolution test apparatus 1 at 100 RPM. The formulation (F37), coated with the ratio of 60:25:15 (Ethocel 7cps: Hypromellose phthalate 50: Hypromellose 5cps), shown the better release of 32% in acid for 1hr, to achieve the loading dose, and the extent of 100% release at 12hr, in pH 6.5 phosphate buffer. Zero-order, first-order, Higuchi, Hixson-Crowell and Korsmeyer peppas models were used to estimate the kinetics of drug release. Drug release kinetics indicated that the drug release was best explained by Higuchi’s equation, as these plots showed the highest linearity (R 2 = 0.9902) indicating the release of drug from matrix as a square root of time dependent process.