Preparation, Physical Characterization, Mechanisms of Drug/Polymer Interactions, and Stability Studies of Controlled-Release Solid Dispersion Granules Containing Weak Base as Active Substance

Abstract

AbstractVerapamil hydrochloride solid dispersion granules were prepared using solvent evaporation technique. Ethyl cellulose, hydroxypropyl cellulose, Eudragit L or Eudragit S were used as polymers for controlling the dissolution rate of the drug substance, and to avoid the continuous decrease of drug dissolution rate at higher pH values. By incorporating Eudragit L in ethyl cellulose network it is possible to prepare controlled-release formulation with increased release rate of active substance (weak base) at higher pH values without causing abrupt drug release at lower pH values. The release rate at low pH values was not highly influenced by Eudragit L content. The behavior of Eudragit L and Eudragit S in coprecipitates was different relating to the solubilization effect and the release of active substance. In order to understand the drug release mechanism better, the release data were tested assuming Higuchi model and first-order kinetic model. Since the calculated correlation coeflcients were very clo...