QUALITATIVE EVALUATION OF THE MECHANISM OF RELEASE OF MATRIX SUSTAINED-RELEASE DOSAGE FORMS BY MEASUREMENT OF POLYMER RELEASE

A method based on size exclusion chromatography and differential viscometric detection was developed for the measurement of polymer concentration in dissolution samples. The method was developed to evaluate the drug release mechanism of matrix sustained release (SR) tablets by comparison of the drug and polymer release profiles. The method was applied to SR dosage forms of flurbiprofen, adinazolam mesylate and alprazolam, which encompass a wide range of drug solubility and formulation composition. SR flurbiprofen tablets exhibit primarily an erosion controlled mechanism as indicated by the superimposable drug and polymer release profiles. SR adinazolam mesylate tablets exhibit an almost entirely diffusion controlled mechanism. Only about 35% of the polymer has dissolved when drug is completely released and the higher variability of the polymer profile is not manifested in the drug release profile. SR alprazolam tablets represent an intermediate case in that both diffusion and erosion contribute to the overall drug release mechanism. About 60-70% of the polymer has dissolved at the end of the dissolution test and the variability of the polymer release data is manifested to a certain extent in the drug release data, particularly between the 4 and 8-h time intervals and for the higher tablet strengths. With increasing dose, erosion appears to contribute to a greater extent to the overall release mechanism. These inferences about the release mechanisms for SR adinazolam mesylate and alprazolam tablets are consistent with and complementary to the conventional approach of modelling the drug release kinetics using the Higuchi and Peppas equations. The measurement of polymer release is a simple and rapid method of estimating the relative contributions of erosion and diffusion to the overall release mechanism.