| Biodegradable DL-Polylactic acid (PLA) microspheres containing quinidine or quinidine sulfate as model compounds were prepared by the solvent evaporation process. The key parameters of this process were identified to elucidate the formation mechanism of the microspheres. The acquired knowledge was then applied to optimize formulation and conditions for preparing drug-loaded PLA microspheres.; The successful entrapment of drug within the microspheres was associated with (a) a fast rate of precipitation of the polymer at the droplet boundary, (b) a low water solubility of the drug in the aqueous phase, and (c) a high concentration of the polymer in the organic phase.; The interaction of the solvent with the polymer, or solvation power, was found to be less influential on the successful entrapment of drug than the interaction of the solvent with the aqueous phase. The construction of a solubility envelope for PLA and an envelope for microsphere formation based on the three-dimensional solubility parameter concept was found to be useful in the interpretation of solvent-nonsolvent-polymer interactions and the formation of PLA microspheres, and in the selection of suitable solvent mixtures.; The delivery system had great flexibility in the design of both rate and duration of drug release. DSC analysis was performed in order to characterize the physical state of the drug within the microsphere structure after microsphere preparation. |
