The interplay of phase inversion, polymer membrane formation, and drug release in a membrane-based delivery system

摘要

The interplay between the dynamics of phase inversion, membrane formation, and drug release kinetics has been studied for solvent-cast films of a poly(n-butyl cyanoacrylate) (PBCA)-naproxen system. Films cast from solutions containing various amounts of polymer, solvent (acetone) and non-solvent (water) were analyzed via electron microscopy to determine optimal compositions and casting conditions leading to the formation of desired porous morphologies. In the presence of drug, the formation and locking-in of porous morphologies are found to be controlled by the interplay between the plasticizing effects of the drug and its crystallization kinetics during the phase inversion. Drug release rates from dried films exhibit a non-monotonic pattern with drug loading (DL), depending on whether a collapsed, dense structure or a porous structure forms. The role of glass transition and crystallization for both as-cast and remelted films is separately analyzed by differential scanning calorimetry (DSC). The discussion includes an analysis of the effect of DL on the quaternary (polymer-solvent-non-solvent-drug) phase diagram, indicating the role of glass composition curves on the locking-in process. (C) 2010 Elsevier B.V. All rights reserved.