On Prednisolone Long-Term Release Mechanism From Biodegradable Polymeric Microspheres

Purpose. The aim of this work was the characterization and investigation of the prednisone release mechanism from biodegradable polymeric microspheres (MS). Methods. Several batches of prednisone loaded poly(lactide-co-glycolide) (PLGA) MS were prepared by a S/O/W method. The MS were characterized in terms of size, morphology, drug content, drug physical state and interaction within the polymeric matrix, and in vitro long-term release. Spectrophotometry, scanning electron microscopy, particle sizing, differential scanning calorimetry (DSC), x-Rays diffraction, and microRaman techniques were used. The obtained release profiles were fitted to Weibull, Power law, Higuchi, and Zero order kinetic models in order to unravel the mechanism governing prednisone release Results. Prednisone was successfully entrapped in PLGA MS (13%-25%). Size was between 20-40 μm and the MS were spherical with an irregular surface and small pores. The MS were able to release prednisone over a period of 3-5 months. RG504H and RG504 MS showed a burst release that was not observed for RG502H MS. Such a behavior suggested a different distribution of the drug within the solid matrix. Moreover, the release rate increased with loading. DSC did not reveal particular interactions between drug and polymer. For RG502H was detected a slight Tg decrease. Diffraction analysis highlighted the presence of intact crystalline prednisone within the MS. MicroRaman spectroscopy showed that in the RG504H and RG504 MS prednisone distributed more on the surface, whereas for RG502H it was mainly located in the core. This explained the high burst release observed for RG504H and RG504 MS. Fitting of the Weibull and power law models confirmed a complex mechanism of release for RG502H MS at lower and higher loading. RG504H and RG504 MS showed a Fickian diffusion driven mechanism which resulted more evident by increasing the loading. The release from RG502H MS fitted perfectly a zero order kinetics while a lower correlation was observed for the Higuchi model. Conclusion. Prednisone loaded PLGA MS were successfully characterized and the anomalous release behavior of the drug from high molecular weight polymer matrices was correlated to a distribution issue within the MS. The release mechanism was also discussed and understood.