The effects of polymer molecular weight on drug release behavior would be more complicated from in situ forming implants (ISFIs) that change gradually from liquid to semi-solid or solid after injection. To investigate this phenomenon, three commercially available D,L-lactic acid-co-glycolic acid (PLGA) polymers with molecular weights of 12, 34, and 48 kDa were used to prepare ISFIs containing leuprolide acetate (LA) as a model peptide. The influence of polymer molecular weight on the membrane formation, morphology, 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 over the first 24 h (36% +/- 0.34%) (burst release), for formulation prepared with polymer RG 503H (medium molecular weight, M(w) 34 kDa), was significantly higher than others (p < 0.05). Surface and cross-section morphology of ISFI prepared with medium molecular weight polymer to cellular and spongy-like structure which was in good agreement with the release behavior of LA from it.
(c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association