Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam

This work, was aimed at evaluating the effects of gamma irradiation on the stability of microspheres made of a poly(lactide-coglycolide) copolymer (PL GA) and loaded with 15% w/w of clonazepam (CLO). The influence of CLO on PL GA radiolysis mechanisms and the identification of possible irradiation mar kers were also investigated. Microspheres were prepared by means of a spray -drying method. gamma Irradiation was carried out either under vacuum or in air, at a dose of 25 kGy, by using a Co-60 source. The stability of CLO lo aded microspheres was evaluated over a 6-month period on the basis of drug content and dissolution profile. Radiolysis mechanisms were investigated by using electronic paramagnetic resonance (EPR) analysis. The microspheres i rradiated under vacuum were stable over the considered period of time. Afte r irradiation in air, CLO release rate increased by similar to 10%, and did not change further in the following period of storage. The EPR analysis sh owed some radicals arising from both the polymeric matrix and the active in gredient. Polymer/CLO spin transfer reactions suggest that CLO had a radio stabilising effect on the polymeric matrix. In the loaded microspheres, the intensity in time of the CLO radical signal is sufficient for its possible use as irradiation marker. (C) 2001 Elsevier Science B.V. All rights reser ved.