Effect of Alcohol on Drug Release Kinetics from HPMC-Based Matrix Tablets Using Model Drugs

Abstract

Drug dissolution testing is routinely used to provide in vitro drug release information for both quality control purposes and drug development. For extended-release (ER) formulations, the dissolution test can serve not only as a quality control tool for the manufacturing process but also as an indicator of how the formulation will perform in vivo to establish an in vitro–in vivo correlation. Hydrophilic matrices are a robust ER formulation technology in which the formation of a viscous hydrated polymer layer at the surface provides a diffusion barrier that retards drug release. Hydroxypropyl methylcellulose (HPMC) is the most widely used polymer for this application. The purpose of this study was to investigate the effect of various proportions of alcohol on in vitro drug release from HPMC-based matrix tablets using three model drugs having different physicochemical properties. The percent drug release increased with increasing levels of alcohol for all three model drugs. It was observed that dose-dumping did not occur for drugs that had low solubility; however, for highly soluble drugs, dumping occurred even at low concentrations of alcohol in the media. The impact of alcohol was prominently observed in terms of initial rapid release for all drugs in the first hour irrespective of the concentration of alcohol. Relative swelling studies of HPMC matrix tablets with and without drug suggest that alcohol retarded hydration and swelling of the polymer. The findings also suggest that the release mechanism changes with an increase in the concentration of alcohol.