Application of the Solid Dispersion Method to Controlled Release of Medicine. II. Sustained Release Tablet Using Solid Dispersion Granule and the Medicine Release Mechanism.

Abstract

In our previous paper, the utility of the solid dispersion for the control of medicine release was studied and the solid dispersion was prepared by the evaporation of ethanol after dissolving a water soluble medicine (oxprenolol hydrochloride), soluble hydroxypropyl cellulose and insoluble ethylcellulose into ethanol. In this paper, the tableting of the above mentioned solid dispersion granule and mechanism of medicine release from this solid dispersion granule were studied. Microcrystalline cellulose was used as the excipient in this tableting. The disintegration time, crushing strength and porosity were measured for the obtained tablets. The pore size distribution in the solid dispersion granules was measured before and after the dissolution test with a mercury porosimeter to clarify the mechanism of medicine release from the granules. The state of medicine in the granules was analyzed by infrared spectrometry, thermal analysis and X-ray diffractometry.As a result, it was clarified that oxprenolol hydrochloride in ethylcellulose was released from the granules by diffusing and dissolving into the medium in the channels formed by the dissolving of hydroxypropyl cellulose and oxprenolol hydrochloride, as inferred in the previous paper. Furthermore, the compression pressure and pH scarcely affected the dissolution behavior of oxprenolol hydrochloride from the granules. It was thought that the homogeneity of the content of oxprenolol hydrochloride in the granules was very high, and the dissolution rate from the granules could be controlled by the particle size of the granules and the composition ratio of ethylcellulose and hydroxypropyl cellulose in the granules. These results suggest the solid dispersion granule and the tablet prepared with this granule are useful for the sustained release granule and tablet.