FORMULATION OF AN INJECTABLE IMPLANT FOR PEPTIDE 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. Itwould be more complicated for in-situ forming injectable implants that change gradually from liquid tosolid after injection. To investigate this phenomenon, two commerciallyaavailable PLGA polymers (lacticacid-co-glycolic acid) with molecular weights of 12000 and 48000 Da were used to prepare injectableimplants containing leuprolide acetate as a model peptide. The influence of polymer molecular weight onthe morphology and erosion of matrices and also on their in-vitro drug release behavior over a period of28 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 highermolecular weight (13%). There was no difference between the steady-state release fluxes of drug from thesystems. Erosion profiles were also in agreement with those of release behavior in both burst and steadystatephases. Electron microscopy studies showed that the lower molecular weight system is more porousthan the higher one, which can explain the difference between burst effects.