Aim To evaluate the effects of an array of
additives on drug release from double-layered
Poly(Lactic-Co-Glycolic Acid) (
PLGA)
matrices. Methods Additives differing in molecular size, hydrophilicity and steric configuration were selected for this study. An anti-proliferative 2-aminochromone, U-86983 (U-86, Pharmacia and Upjohn), was used as a model agent because of our interest in investigating local drug delivery systems for the inhibition of
restenosis. Results In vitro release of U-86 from PLGA matrices without additive showed a typical biphasic release
kinetics, i.e. a slow diffusion release (Phase I) followed by a fast erosion-mediated release (Phase II). The water-
soluble additives in PLGA matrices changed the biphasic release pattern to a near monophasic profile by increasing the release rate of the Phase I. Increasing the ratio of additives to PLGA in matrices caused a significant increase in the U-86 release rates. A high molecular weight water-soluble additive, Pluronic F127, resulted in a matrix showing perfect zero-order release kinetics. The morphologic evaluation of matrices using scanning electron microscopy indicated that the water-soluble additives were leachable and thus generated a highly porous structure in the matrices. Conclusion Water-solubility, molecular size and steric configuration of the additives are the important determinants in generating various types of pore structures in polymer matrix which in turn affect the release mechanism and release kinetics.