Degradation of DL-PLA-methadone microspheres during in vitro release

The in vitro degradation of polylactic acid of different weight average molecular weight (M(w)) in microspheres containing variable amounts of methadone base (between 17 and 47%) was studied using the degradation index (DI), polidispersivity (pd) and molecular weights distribution. Both pd and DI are independent of initial methadone content and increase with M(w) polymer, showing values of DI around 6.6 for the high M(w) and 2.9 for the lower M(w). The distribution functions in the number of the molecular weights during the degradation assays indicate the presence of different break mechanisms for high and low molecular weight chains. A semiempiric model is proposed to explain the evolution of M(n) during degradation in function of the number of bonds available for their breaking and hydrolysis rate constant. The first parameter ranges between 2.35 and 6.65 in function of M(w); the hydrolysis rate constant is independent of M(w) and equal to 0.020 h(-1) (SD = 0.011 h(-1)).