Application of the Solid Dispersion Method to the Controlled Release of Medicine. V. Suppression Mechanism of the Medicine Release Rate in the Three-Component Solid Dispersion System.

Abstract

Solid dispersions were prepared with a highly water soluble medicine (oxprenolol hydrochloride (OXP)), water insoluble ethylcellulose (EC) and water soluble hydroxypropyl cellulose (HPC). The release profiles of OXP from the solid dispersion granules at various composition ratios of the components, and the suppression mechanism of the release rate in the OXP-EC-HPC system, were studied.The release rate of OXP reached a minimum level at the HPC composition ratio of 5-10%. It was difficult to control the release rate with more than 10% HPC. It was found that a marked decrease in the release rate at the HPC composition ratio of 5-10% was caused by the formation and retention of the swelled phase of HPC in the EC matrix. At more than 10% HPC, because OXP molecules enclosed by HPC molecules or incorporated in the swelled HPC phase increased and most of the OXP molecules were released together with HPC by erosion, the release rate of OXP increased drastically in the early stages of the release process. At the OXP composition ratio of 30% or more, the diameter and volume of the pores formed by the OXP release markedly increased, since the aggregates of OXP molecules that showed crystallinity began to be formed in the solid dispersion.