The interplay of membrane formation and drug release in solution-cast films of polylactide polymers

The interplay of phase inversion and drug release has been studied for films of several biodegradable polylactide polymers cast from solutions containing polymer, solvent, and drug (naproxen). Variables studied included polymer type and concentration, solvent type, and film casting conditions (i.e. free or forced convection, humidity). Film morphologies and thermal properties indicate that reduction of the T-g of the amorphous poly (lactide-co-glycolide) (PLGA) and Poly (D, L-lactide) (PDLLA) systems caused by the drug, inhibits stabilization of a porous, structure, regardless of dry casting conditions and drug loads. Porous membranes could be formed by wet casting; however, drug loss during casting, makes this a non-viable process. For semi-crystalline PLLA, membrane morphologies could be varied by controlling the mass transfer path to form a single-phase dense film by polymer crystallization or a liquid-liquid two-phase structure followed by locking-in by polymer crystallization. However, the lack of drug solubility in the crystalline phase leads to unfavorable drug distributions most often leading to a burst release. Release profiles for all three polymers were found to follow a two-stage release model, with a first stage diffusive release followed by zero-order release in the second stage due to polymer erosion. (C) 2009 Elsevier B.V. All rights reserved.