Application of the Solid Dispersion Method to the Controlled Release of Medicine. VIII. Medicine Release and Viscosity of the Hydrogel of a Water-Soluble Polymer in a Three-Component Solid Dispersion System.

Abstract

Solid dispersions were prepared with a highly water-soluble medicine (oxprenolol hydrochloride (OXP)), water-insoluble ethylcellulose (EC) and four grades of water-soluble hydroxypropylcellulose (HPC) having different molecular weights. The effects of the composition ratio within the range of 5% of HPC and of the viscosity of HPC hydrogels on the release of OXP were studied. The bulk viscosity of HPC hydrogels was evaluated from the relationship between shear rate and shear stress. The microscopic viscosity was evaluated by the spin probe method of the electron spin resonance (ESR) technique.The release rate of OXP decreased with increasing HPC composition ratio and became almost constant at the HPC composition ratio of 3% and more. This result suggests that the release of OXP will occur through its diffusion into the swollen HPC gel phase formed in a solid dispersion at the HPC composition ratio of 3% and more. The bulk viscosity of HPC hydrogels markedly increased with increasing molecular weight of HPC, but there was little noticeable change in release rate and activation energy for the diffusion of OXP. This result can be explained by the fact that the microscopic viscosity was hardly affected by the molecular weight of HPC, suggesting that the resistance to diffusion of OXP into the swollen HPC gel phase in the solid dispersion was almost the same regardless of the moleclar weight of HPC.