Effect of Gamma-Irradiation on Biodegradable Microspheres Loaded With Rasagiline Mesylate

Abstract

In the present study, the influence of gamma-irradiation was evaluated on the physicochemical characteristics and in vitro release of rasagiline mesylate (RM), a selective MAO-B inhibitor used in Parkinson's disease, from poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Microspheres were prepared using PLGA 50:50 by the solvent evaporation technique (O/W emulsion). Microspheres were sterilized by gamma-irradiation and their influence was assessed by scanning electron microscopy (SEM), laser light diffraction, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gel permeation chromatography (GPC), encapsulation efficiency (EE) and in vitro drug release. Gamma-irradiation of RM-loaded microspheres did not affect EE, DSC and XRD patterns. After gamma-irradiation, changes on the surface were observed by SEM, but no significant difference in mean particle size was observed. GPC measurements showed a decrease in molecular weight of the polymer after five days of in vitro release. The similarity factor value between irradiated and non-irradiates microspheres was <50, indicating the non-similarity of the release profiles. The sterilization technique had an effect on the integrity of polymeric system, significantly affecting in vitro release of RM from PLGA microspheres. Therefore, from our results we conclude that gamma-irradiation is not a suitable sterilization procedure for this formulation.

Potential Roles of the Glass Transition Temperature of PLGA Microparticles in Drug Release Kinetics

“…The bupivacaine release rates from PLGA microparticles increased by 50% after sterilization, but they were less affected by e-beam than γ-radiation . A similar extent of faster release was also observed with rasagiline mesylate . 17β-Estradiol-loaded microparticles were prepared by spray drying the mixture of the drug and PLGA, followed by γ-irradiation at −78.5 °C using dry ice.…”

Scalable production of microscopic particles for biological delivery

“…, PLGA), and affect the overall characteristics of the nanoformulation itself. 158–161 However, there have also been publications reporting that gamma irradiation caused no significant changes to PLGA particle-based drug formulations. 161,162 If gamma irradiation, ultraviolet light, and autoclaving are found to be problematic, an alternative method can be sterile filtration of the final product.…”

“…157 Sterilization procedures such as gamma irradiation, ultraviolet light, or autoclaving could be detrimental to sensitive active pharmaceutical ingredients (APIs), cause chain alteration of polymers (e.g., PLGA), and affect the overall characteristics of the nanoformulation itself. [158][159][160][161] However, there have also been publications reporting that gamma irradiation caused no significant changes to PLGA particle-based drug formulations. 161,162 If gamma irradiation, ultraviolet light, and autoclaving are found to be problematic, an alternative method can be sterile filtration of the final product.…”