Effects of storage on the physicochemical properties and release characteristics of progesterone-loaded poly( l-lactide) microspheres

Abstract

Changes in the physicochemical properties of poly( l-lactide) microspheres that occurred during storage were studied by X-ray powder diffraction, differential scanning calorimetry and scanning electron microscopy, in order to elucidate the factors that affect the stability of drug release characteristics. Progesterone-loaded microspheres with amorphous polymer matrices were stored at 50 and 30°C under desiccated and moist atmospheres. The surface morphology did not change significantly during storage under any of the conditions studied. Storing the microspheres at a temperature above the glass transition temperature ( T g ) of the polymer under moist conditions caused polymer matrix crystallization. The drug release rate of stored microspheres was faster than that of microspheres before storage, which indicates that matrix crystallization increased the drug release rate. In contrast, the polymer matrices of microspheres stored at a temperature below the T g remained amorphous after 7 months storage under both moist and desiccated conditions. The T g of microspheres stored at a high relative humidity decreased considerably during storage, which may be attributable to the plasticizing effect of water absorption by microspheres as well as to the decreased polymer molecular weight resulting from decomposition of polymer molecules. The drug release of microspheres stored under moist conditions was faster than that of those stored dry and appeared to correlate with the polymer matrix T g . The hydrolysis of polymer molecules may decrease the rigidity of the polymer matrices, as indicated by the decrease in the T g . This may result in rapid drug release.