Gamma irradiation effects on poly(DL-lactictide-co-glycolide) microspheres

Gamma radiation treatment plays an increasingly important role in the steri lization/sanitization of pharmaceutical products. However, irradiation may affect the stability of the product and thus its safety of use. We investig ated the influence of ionizing radiation on modified release microparticula te drug delivery systems made of two types of polylactide-co-glycolide copo lymers (PLG): RG 503 and RG 503H; these polymers have identical molecular w eights but different chemical structures. The effect of gamma radiation on polymer stability of the raw polymers (P) and related microspheres (Ms) was evaluated. Samples were irradiated at different irradiation doses (5, 15 a nd 25 kGy) using Co-60 as radiation source. The microspheres were prepared using the spray drying technique. Degradation of PLG and related microspher es was evaluated during six months in terms of average molecular weight (M- w) loss by gel permeation chromatography (GPC) and variation in glass trans ition temperature (T-g) using differential calorimetry (DSC). The presence of free radicals in the product was tested by electron paramagnetic resonan ce (EPR). Both P and Ms showed a trend in decreasing their M-w at time 0 as a function of irradiation dose. For RG503 the decay in M-w is always negli gible for doses below 15 kGy while it is about 10% for 25 kGy. After 150 da ys M-w decay was 25% in the microspheres and 20% in the raw polymer. It was not possible to evaluate the radiation effect, at different storage times, for RG503H because this polymer resulted to be unstable even in the regula r storage conditions without being irradiated. The concentration of radiati on-induced free radicals was higher in RG 503H (both P and Ms) and they wer e more stable than the free radicals species observed in the case of polyme r RG 503. Alterations and/or production of new radicals were observed on ex posure of RG 503H microspheres to the light. Radiolytic degradation of RG 5 03 under vacuum is characterized by a prevalence of the chain scission even ts leading to a decrease of M-w. Some crosslinking can occur mainly in the post irradiation stage through the decay and coupling of the hydrogen abstr action radicals. A hydroperoxydative cycle, whose mechanism is suggested, i s generated in the presence of oxygen. (C) 1998 Elsevier Science BN. All ri ghts reserved.