Controlled release of nalbuphine prodrugs from biodegradable polymeric matrices: influence of prodrug hydrophilicity and polymer composition

The objective of this work was to assess the effects of nalbuphine prodrug hydrophilicity and lactide/glycolide copolymer ratio on drug release from lactide/glycolide based polymeric matrices. A panel of four nalbuphine prodrugs with various ester chains were incorporated into poly (d,l-lactide) based matrices by using the solvent evaporation method. Drug release rates for the matrices were found to be a function of prodrug hydrophilicity, with higher drug release rates for matrices with more hydrophilic prodrugs. Data analysis using the Higuchi expression indicated that the release of various prodrug from poly (d,l-lactide) based matrices was consistent with a diffusion mechanism. The prodrug release rate constants derived from the Higuchi expression correlated well with prodrug solubilities. In the second part of the study, the effect of lactide/glycolide copolymer ratio on nalbuphine propionate release was studied. The drug release rate and matrix hydration rate were found to be a function of copolymer ratio, with faster drug release and matrix hydration for matrices with lower lactide/glycolide ratio copolymers. The nalbuphine propionate release profiles fit well to the Higuchi expression, indicating that drug release from the Poly (d,l-lactide-co-glycolide) based matrices was consistent with a diffusion mechanism. The drug release rates correlated well with matrix hydration rates, suggesting that different polymer compositions may attribute to various matrix hydration and therefore affect drug release from the PLGA matrices. Copyright (C) 1998 Elsevier Science B.V.