MECHANISM OF DIFFUSION OF MONOSUBSTITUTED BENZOIC-ACIDS THROUGH ETHYLENE-VINYL ACETATE COPOLYMERS

Ethylene-vinyl acetate (EVAc), a biocompatible copolymer, has been employed as the rate-controlling membrane in several drug delivery systems. To study the mechanism(s) of diffusion of drugs through EVAc membranes, the diffusion, permeability, and partition coefficients of monosubstituted benzoic acids were studied as a function of vinyl acetate content. The diffusion coefficients were found to occupy a narrow range, but the permeability and partition coefficients were found to increase in a nonlinear fashion as a function of vinyl acetate content, indicating that the diffusion process was partition governed. The partitioning data were analyzed on the basis of the partitioning between the vinyl acetate moiety and the aqueous phase, assuming the formation of 1:1 benzoic acid:vinyl acetate complexes. The effects of ionization and the addition of 2-propanol to the diffusion medium were studied. The results suggest that the un-ionized neutral forms of the benzoic acids are responsible for transport across the copolymer. Altering the composition of the medium by addition of 2-propanol increased the donor phase solubility of the acid, the steady-state rate, and the permeability, suggesting that cosolvent modification provides an excellent chemical means to increase release rates.