POLYMER EROSION AND DRUG-RELEASE CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE MATRICES

Polymer erosion of matrices of similarly substituted hydroxypropyl met hylcellulose (HPMC) polymers was examined, and drug release in terms o f diffusion and erosion contributions was characterized, focusing on m atrices containing either polymer alone or a drug content of 25% level with no added excipients. A novel approach was utilized to separate d iffusional and erosional contributions to drug release. Diffusional dr ug release was determined by fitting release data versus (time)(0.45), and the drug release due to erosion was quantified by subtracting the percent predicted for diffusional drug release from the total drug re lease at each specific time point. Drug release resulting from polymer erosion was linear versus time and was found to be a function of the number average molecular weight of the polymer. In contrast, diffusion al release rates were comparable for all HPMC grades studied and, thus , were independent of number average molecular weight of the polymers studied. Under stirring conditions of 10-100 rpm as well as static con dition, the detachment of individual polymer chains at the matrix surf ace occurred at a faster rate relative to diffusion away from the matr ix surface. The erosion study indicated that polymer diffusion of the HPMC polymer chains through the aqueous diffusion layer was the rate-l imiting step for polymer erosion. In general, polymer erosion was foun d to be inversely related to the polymer number average molecular weig ht. A scaling law was used to relate polymer erosion rate with the res pective polymer number average molecular weight. Similar relationships were obtained for matrices with and without drug at a stirring rate o f 100 rpm.