Formulation of an injectable implant for peptid delivery and mechanistic study of the effect of polymer molecular weight on its release behavior

The effects of polymer molecular weight on drug release from erodible matrices are not well known. It would be more complicated for in-situ forming injectable implants that change gradually from liquid to solid after injection. To investigate this phenomenon, two commerciallyaavailable PLGA polymers (lactic acid-co-glycolic acid) with molecular weights of 12000 and 48000 Da were used to prepare injectable implants containing leuprolide acetate as a model peptide. The influence of polymer molecular weight on the morphology and erosion of matrices and also on their in-vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released (32%) over the first 24 hours (burst phase) for 12 kDa PLGA system, was significantly (P<0.05) higher than that of the one higher molecular weight (13%). There was no difference between the steady-state release fluxes of drug from the systems. Erosion profiles were also in agreement with those of release behavior in both burst and steady-state phases. Electron microscopy studies showed that the lower molecular weight system is more porous than the higher one, which can explain the difference between burst effects.