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Gamma irradiation effects on poly(DL-lactictide-co-glycolide) microspheres
L Montanari1, M Costantini, E C Signoretti
1Istituto di Chimica Farmaceutica, Università degli Studi di Milano, V. le Abruzzi 53, 20131 Milano, Italia. montana@imiucca.csi.unimi.it
Summary
Gamma radiation affects polylactide-co-glycolide (PLG) drug delivery systems, with RG 503 showing minimal molecular weight loss below 15 kGy. RG 503H proved unstable, exhibiting higher free radical concentrations and light sensitivity.
Area of Science:
- Pharmaceutical Sciences
- Polymer Chemistry
- Radiation Chemistry
Background:
- Gamma radiation is crucial for sterilizing pharmaceutical products.
- Irradiation can compromise product stability and safety.
- Modified-release drug delivery systems require careful stability assessment post-irradiation.
Purpose of the Study:
- To investigate the impact of gamma radiation on the stability of polylactide-co-glycolide (PLG) modified-release microparticulate systems.
- To compare the radiation effects on two PLG copolymers (RG 503 and RG 503H) with identical molecular weights but different chemical structures.
- To evaluate polymer degradation, free radical formation, and stability over time after irradiation.
Main Methods:
- PLG microspheres (RG 503 and RG 503H) were prepared via spray drying.
- Samples (raw polymers and microspheres) were irradiated with gamma rays (60Co) at doses of 5, 15, and 25 kGy.
- Degradation was assessed by measuring average molecular weight (Mw) loss using gel permeation chromatography (GPC) and glass transition temperature (Tg) changes using differential scanning calorimetry (DSC) over six months.
- Electron paramagnetic resonance (EPR) was used to detect and characterize free radicals.
Main Results:
- Both RG 503 polymers and microspheres showed decreased Mw with increasing irradiation dose, with negligible loss below 15 kGy for RG 503.
- RG 503 microspheres exhibited 25% Mw decay after 150 days, compared to 20% for the raw polymer.
- RG 503H was inherently unstable, showing high, stable free radical concentrations, and radical alterations upon light exposure; its radiation effects could not be reliably assessed.
- Radiolytic degradation of RG 503 under vacuum primarily involved chain scission, while oxygen presence suggested a hydroperoxydative cycle.
Conclusions:
- Gamma irradiation at doses up to 15 kGy has a limited impact on the stability of RG 503-based microparticulate drug delivery systems.
- RG 503H is unsuitable for gamma irradiation due to its inherent instability and high susceptibility to radical formation and light-induced degradation.
- Understanding radiolytic degradation pathways is crucial for ensuring the safety and efficacy of irradiated pharmaceutical drug delivery systems.