Influence of PLGA molecular weight distribution on leuprolide release from microspheres.

Poly (lactide-co-glycolide) (PLGA) is a biodegradable copolymer used in many long-acting drug products. The objective of the present study was to investigate the influence of polymer molecular weight distribution differences of PLGA on the in vitro release profile of leuprolide acetate microspheres. Eight microsphere formulations were prepared using the same manufacturing process but with different PLGA polymers. The physicochemical properties (drug loading, particle size and morphology) as well as the in vitro release profiles of the prepared microspheres were evaluated using a sample-and-separate method. The amount of burst release increased with increasing amount of low molecular weight fractions of PLGA, indicating that the drug release profiles appeared to be affected not only by the average molecular weight but also the molecular weight distribution of PLGA. In conclusion, quality control of the molecular weight distribution of PLGA as well as the weight average molecular weight is highly desirable in order to control the burst release.