The effect of PLGA molecular weight differences on risperidone release from microspheres

The objective of the present study was to investigate the effect of molecular weight differences of poly (lactic-co-glycolic acid) (PLGA) on the in vitro release profile of risperidone microspheres. Four different PLGA molecular weights were investigated and all the microsphere formulations were prepared using the same manufacturing process. Physicochemical properties (particle size, drug loading, morphology and molecular weight) as well as in vitro degradation profiles of the prepared microspheres were investigated in addition to in vitro release testing. The in vitro release tests were performed using a previously developed flow through cell (USP apparatus 4) method. The particle size of the four prepared microsphere formulations varied, however there were no significant differences in the drug loading. Interestingly, the in vitro release profiles did not follow the molecular weight of the polymers used. Instead, the drug release appeared to be dependent on the glass transition temperature of the polymers as well as the porosity of the prepared formulations. The catalytic effect of risperidone (an amine drug) on PLGA during manufacturing and release testing, minimized the differences in the molecular weights of the four formulations, explaining the independence of the release profiles on PLGA molecular weight.