Modulation of pH-Independent release of a Class II Drug (Domperidone) from a polymeric matrix using acidic excipients

Abstract

Drug release from polymeric matrix systems is the rate-limiting step for drug bioavailability and is determined by drug solubility, most drugs show pH-dependent solubility. Polymeric matrices remain in the gastrointestinal tract for a longer period of time and are exposed to environments of varying pH, which can adversely affect drug release. In the present study, the pH-independent drug release of domperidone was achieved by modifying the microenvironmental pH of a swollen polymeric matrix using acidic excipients (citric acid and tartaric acid). Matrices were prepared by a water-based, wet-granulation technique and evaluated for various official and unofficial parameters. In vitro drug release was studied using USP dissolution apparatus and pH 6.80 phosphate buffer as dissolution medium. Release kinetics was evaluated according to various mathematical models. Results show that domperidone release can be effectively modified by inclusion of acidic excipients in the formulations. Acidic excipients modulated microenvironmental pH and avoided the effect of dissolution medium pH on drug release. The resultant formulations are easy to prepare and scale up for commercial manufacturing. Better pH-independent release, following zero-order kinetics, was achieved with tartaric acid.