Application of the Solid Dispersion Method to the Controlled Release of Medicine. VI. Release Mechanism of a Slightly Water Soluble Medicine and Interaction between Flurbiprofen and Hydroxypropyl Cellulose in Solid Dispersion.

Solid dispersion (SD) was prepared with a slightly water soluble medicine (flurbiprofen (FP)) and a water soluble polymer (hydroxypropyl cellulose (HPC)) having five grades of different molecular weights. The release mechanism of FP from the SD granules and the interaction between FP and HPC in the SD were studied.The release rate of FP from the SD granules increased with decreasing HPC molecular weight or increase in the composition ratio of HPC. The powder X-ray diffraction patterns and DSC curves suggest that FP exists in an amorphous state in the SD. The IR spectra show an interaction of hydrogen bonding between FP and HPC. The percent of FP forming a hydrogen bond with HPC in the SD increased with decreasing HPC molecular weight or increase in the composition ratio of HPC. A linear relationship was found between the release rate of FP and the percent of the hydrogen bonded FP in the SD. An increase in the dispersibility of FP and the degree of mixing of FP and HPC will cause an increase in the effective surface area of FP and HPC for dissolution, thus increasing the release of FP and the percent of hydrogen bonded FP.