The Effect of Citric Acid Added to Hydroxypropyl Methylcellulose (HPMC) Matrix Tablets on the Release Profile of Vinpocetine

Abstract

Vinpocetine is a pH-dependent experimental drug with a short half-life. The sustained-release matrix tablets of vinpocetine were prepared by direct compression using hydroxypropyl methylcellulose (HPMC) and different amounts of citric acid to set up a system bringing about gradual release of this drug. In order to investigate the influence of citric acid and the pH value of medium on the drug release from HPMC matrix tablets, an in vitro release test was carried out in either phosphate buffer pH 6.8 [0.5% sodium dodecyl sulfate (SDS)] for 12 hr or in 0.1 N HCl (0.5% SDS) (0-2 hr) and phosphate buffer pH 6.8 (0.5% SDS) (2-12 hr). Dissolution curves were described by the Peppas equation: M(t)/M(inf)=ktn, and the influence of citric acid on the dissolution mechanism was estimated according to the regression parameter-n and k values. The addition of citric acid and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing the amounts of citric acid produced an increase in drug release rate, which showed a good linear relationship between contents of citric acid and drug accumulate release (%) in phosphate buffer pH 6.8 (0.5% SDS) (r>0.99). Moreover, a higher drug release rate could be found in 0.1 N HCl (0.5% SDS) than that in phosphate buffer pH 6.8 (0.5% SDS) during the first two hours when the content of citric acid added to matrices was lower than 45 mg/tab., but no significant difference could be found when the content of citric acid was above that value. Increasing amounts of citric acid produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a trend favoring the mechanism of diffusion with the addition of increasing quantities of citric acid.