Abstract
Carmofur-loaded microspheres composed of polylactic acid (PLA) with a molecular weight of 20, 000 were prepared as a parenteral dosage form applicable as a sustained release preparation for cancer chemotherapy by a solvent evaporation method on a clean bench in a biological clean room. The amount of residual organic solvent in the microspheres was determined, and the physicochemical characteristics including the release of the drug from the microspheres were also investigated. The periods required to evaporate the methylene chloride remained in the microspheres below 100 ppm at 30, 35 and 40°C were 35, 9 and 5 days, respectively. The shape of microspheres was completely spherical and the surface was found to be quite smooth by scanning electron microscopic observation. Particles with diameter of 20 to 100 μm occupied about 85% of all microspheres, and the mean diameter of the microspheres dried at 35 and 40°C was about 60-80 μm. The release of the drug from the microspheres was relatively sustained, and it took 14 days to release more than 90%. In the sterility test, no growth of microorganism was not observed and thus the microspheres prepared under the biologically clean condition were confirmed to be aseptic. These findings suggest that the present PLA microspheres containing carmofur may be applicable as sustained-release preparation for the cancer chemotherapy.
