In vitro evaluation of the hydrolytic degradation of dispersed and aggregated poly(DL-lactide-co-glycolide) microspheres

Release and degradation profiles of nifedipine-loaded poly(DL-lactide-co-glycolide) microspheres were evaluated as a function of microsphere size and drug content. In a first stage, individualized microspheres were incubated in order to investigate drug release and polymer hydrolysis in the same conditions. The nifedipine release was completed within 15 days and, after a 1-day burst effect, the profiles obtained were almost linear for 18 mu m microspheres, and biphasic for 80 mu m microspheres. The degradation pattern of individualized microspheres showed that neither drug content nor microsphere size influenced the degradation rate. Weight loss measurements showed that the onset of polymer mass loss only occurred after complete nifedipine release. It appears from these results that nifedipine release is controlled by diffusion phenomena. In the second part of this investigation, microspheres were maintained aggregated during incubation in order to mimic the in vivo depot formed after i.m. or s.c. injection. The degradation rate of aggregated microspheres was higher than that of dispersed ones because of acidic autocatalysis of polymer hydrolysis. No difference was observed between degradation rates of microspheres prepared with various nifedipine contents.