Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles

Because of the importance of in vitro release tests in establishing batch-to-batch reproducibility and in vitro-in vivo correlation, this study investigated the influence of agitation regimen on the in vitro release behavior of leuprolide from poly(lactic-co-glycolic) acid microparticles. Leuprolide-loaded microspheres were prepared using Resomer(®) RG502H and RG503H as polymers. Leuprolide in vitro release was performed in phosphate buffer solution under continuous or once-a-week agitation. At predetermined intervals, leuprolide release, polymer mass loss, and degree of hydration were investigated. Leuprolide release and polymer mass loss were higher under continuous agitation with respect to that under intermittent agitation. Using a modified version of Koizumi equation, it was possible to fit leuprolide release profiles. Similarity factor comparison showed a high level of similarity between experimental and modeled data in the case of once-a-week agitation regimen. This work highlights the importance of the in vitro release conditions on peptide release behavior from polyester microparticles.