PLGA microsphere bioburden evaluation for radiosterilization dose selection.

The aim of this study was to determine the bioburden of PLGA microspheres produced by the solvent emulsion/extraction process as a means of determining an appropriate gamma-irradiation dose for sterilization. Bioburden was evaluated on the basis of ISO specifications. The analysis of initial microbial contamination was performed on blank microspheres, prepared by a non-aseptic laboratory scale process. A mean bioburden of 36.04 CFU (colony forming units)/110 mg microspheres was determined. Most of the detected germs originated from human commensal flora. According to the ISO dose-selection method, a gamma-irradiation dose of 19.6 kGy was found sufficient to ensure a sterility level of 10(-6). The effect of the selected irradiation dose on both the molecular weight of the polymer and the kinetics of 5-fluorouracil drug release from the microspheres was compared to the European Pharmacopeia recommended irradiation dose (25 kGy). This 20% reduced dose showed a lower extent of molecular weight reduction of PLGA and a better control of 5-FU release from microparticles. This can be related to reduce polymer radiation damage.