Gamma irradiation effects on poly(DL-lactictide-co-glycolide) microspheres
| Autor: | Luisa Valvo, Monica Bartolomei, Sandro Onori, Elena Ciranni Signoretti, Luisa Montanari, Antonio Faucitano, Mara Santucci, Bice Conti, Monica Costantini, Ida Genta, Paola Fattibene |
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| Rok vydání: | 1998 |
| Předmět: |
Free Radicals
Polymers Radical Pharmaceutical Science Biocompatible Materials Ionizing radiation Gel permeation chromatography Drug Stability Polylactic Acid-Polyglycolic Acid Copolymer Polymer chemistry Irradiation Lactic Acid chemistry.chemical_classification Calorimetry Differential Scanning Chemistry Electron Spin Resonance Spectroscopy Sterilization Polymer Radiation effect Microspheres Molecular Weight Oxygen Gamma Rays Radiolysis Microscopy Electron Scanning Molar mass distribution Polyglycolic Acid Nuclear chemistry |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 56(1-3) |
| ISSN: | 0168-3659 |
| Popis: | Gamma radiation treatment plays an increasingly important role in the sterilization/sanitization of pharmaceutical products. However, irradiation may affect the stability of the product and thus its safety of use. We investigated the influence of ionizing radiation on modified release microparticulate drug delivery systems made of two types of polylactide-co-glycolide copolymers (PLG): RG 503 and RG 503H; these polymers have identical molecular weights but different chemical structures. The effect of γ radiation on polymer stability of the raw polymers (P) and related microspheres (Ms) was evaluated. Samples were irradiated at different irradiation doses (5, 15 and 25 kGy) using 60 Co as radiation source. The microspheres were prepared using the spray drying technique. Degradation of PLG and related microspheres was evaluated during six months in terms of average molecular weight ( M w ) loss by gel permeation chromatography (GPC) and variation in glass transition temperature ( T g ) using differential calorimetry (DSC). The presence of free radicals in the product was tested by electron paramagnetic resonance (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 negligible for doses below 15 kGy while it is about 10% for 25 kGy. After 150 days 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 regular storage conditions without being irradiated. The concentration of radiation-induced free radicals was higher in RG 503H (both P and Ms) and they were more stable than the free radicals species observed in the case of polymer RG 503. Alterations and/or production of new radicals were observed on exposure of RG 503H microspheres to the light. Radiolytic degradation of RG 503 under vacuum is characterized by a prevalence of the chain scission events 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 abstraction radicals. A hydroperoxydative cycle, whose mechanism is suggested, is generated in the presence of oxygen. |
| Databáze: | OpenAIRE |
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