Gamma irradiation for terminal sterilization of 17beta-estradiol loaded poly-(D,L-lactide-co-glycolide)...

17beta-Estradiol-loaded microparticles using poly-(D, L-lactide-co-glycolide) polymer (PLG) were prepared by a modified spray-drying method and the effects of gamma-irradiation on drug substance, polymer and microparticles were investigated. Irradiation doses ranging from 5.1 to 26.6 kGy were applied using a 60Co-radiation source. 17beta-Estradiol drug substance showed excellent stability against gamma-irradiation in the investigated dose range, whereas microencapsulated estradiol seems to be converted to conjugation products with PLG, and to a lesser extent to the degradation product 9,11-dehydroestradiol. The weight-average molecular weight of the PLG polymers decreased with increasing irradiation dose while polydispersity indices (M(w)/M(n)) remained nearly unchanged, compatible with a random chain scission mechanism in lactide/glycolide-copolymer degradation. In vitro drug release studies showed accelerated kinetics with increasing irradiation doses due to dose dependent polymer degradation. Microbiological process monitoring showed decreasing bioburden with increasing spraying time, which was successfully further reduced by applying irradiation sterilization. Microencapsulated test spore suspensions of Bacillus pumilus ATCC 27142, the official test specimen for the gamma-sterilization process, revealed effective reduction of bioburden, confirming its published D(10) value. In conclusion, our studies demonstrated efficacy of gamma-irradiation as terminal sterilization method for poly-(D,L-lactide-co-glycolide) polymer-based drug delivery systems. The sterilization conditions need to be carefully adjusted for the final dosage form.