EFFECT OF TEMPERATURE ON MECHANISMS OF DRUG-RELEASE AND MATRIX DEGRADATION OF POLY(D,L-LACTIDE) MICROSPHERES

Drug release and matrix degradation of poly (D,L-lactide) microspheres with different glass transition temperatures (T-g) were investigated at various temperatures in order to clarify the effect of temperature on mechanisms of drug release and matrix degradation. At temperatures above T-g, the average molecular weight of the polymer decreased markedly during drug release. Progesterone release was faster than microsphere weight loss, and could be fitted to the Higuchi equation. These results suggest that diffusion from the bulk of the matrix contributed to drug release at temperatures above T-g. In contrast, at temperatures below the T-g of the microspheres, the average molecular weight of the polymer did not change throughout the experimental period and matrix degradation was restricted to the matrix surface. Release of progesterone was due mainly to surface erosion. These results suggest that, even in the case of polylactide, drug release can be controlled only by surface erosion.