Paclitaxel loaded poly(l-lactic acid) (PLLA) microspheres; II. The effect of processing parameters on microsphere morphology and drug release kinetics.

摘要

The kinetics of solvent removal in microsphere preparation and their effect on the morphology and release characteristics of paclitaxel-loaded PLLA microspheres were determined. Microspheres were analyzed by SEM and DSC and in vitro paclitaxel release was monitored by HPLC. During manufacture, dichloromethane evaporated at a constant rate, which increased with dispersion stirring speed and decreased with increasing paclitaxel content. Paclitaxel-loaded microspheres had a dimpled surface, due to surface deposition of the drug, while controls were smooth. In the formation of larger microspheres, the deposition of drug in the surface slowed the solidification process resulting in drug-loading dependent thermal properties. Paclitaxel release did not follow diffusion kinetics, rather it was characterized by a large burst followed by a linear phase. We speculate that non-uniform (surface-rich) drug distribution in the microspheres may contribute to the deviation from the theoretical pattern of kinetics for diffusion from a sphere.