APPLICATION OF THE SOLID DISPERSION METHOD TO THE CONTROLLED-RELEASE OF MEDICINE .4. RELEASE MECHANISM OF A SLIGHTLY WATER-SOLUBLE MEDICINEAND INTERACTION BETWEEN FLURBIPROFEN AND HYDROXYPROPYL CELLULOSE IN SOLID DISPERSION

Solid dispersion (SD) was prepared with a slightly water soluble medic ine (flurbiprofen (FP)) and a water soluble polymer (hydroxypropyl cel lulose (HPC)) having five grades of different molecular weights. The r elease mechanism of FP from the SD granules and the interaction betwee n FP and HPC in the SD were studied. The release rate of FP from the S D 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 PP exists in an amorphous state in the SD . The IR spectra show an interaction of hydrogen bonding between PP an d HPC. The percent of FP forming a hydrogen bond with HPC in the SD in creased with decreasing HPC molecular weight or increase in the compos ition ratio of HPC. A linear relationship was found between the releas e rate of FP and the percent of the hydrogen bonded FP in the SD. An i ncrease 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 HP C for dissolution, thus increasing the release of FP and the percent o f hydrogen bonded FP.