Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. II. Some process parameters influencing the preparation and properties of microspheres

Abstract

D,L-polylactic acid (PLA) microspheres containing quinidine base and quinidine sulphate were prepared by the solvent evaporation method. The present study was carried out to examine how various process parameters in the aqueous phase influenced the preparation and properties of PLA-microspheres. The amount of drug that could be incorporated into the microspheres depended primarily on the solubility of the drug in the aqueous phase and the precipitation of PLA at the droplet surface. The drug content was found to be influenced by the organic solvent: aqueous phase ratio, the temperature of the aqueous phase, and the amount of emulsifying agent. Time-dependent pH-change studies in the aqueous phase showed that polymer precipitation at the outer surface of the microspheres, and drug loss due to partitioning, occurred rapidly. A partition method for increasing the payload of drug in the microspheres was developed by incorporating drug in both the aqueous and the organic phases. Using this method, drug could be loaded into the microspheres independent of the pH of the aqueous media. The partition method circumvented the surface degradation observed with PLA microspheres prepared at high pH values of the aqueous phase. This method may prove useful for the entrapment of water-soluble drugs.