Drug diffusion in hydrophobically modified N,N-dimethylacrylamide hydrogels

Abstract

The use of hydrophobically modified hydrogels for drug release was investigated. Copolymers of N,N-dimethylacrylamide and 2-(N-ethyl-perfluorooctanesulfonamido) ethyl acrylate (FOSA) were prepared by free-radical polymerization. The drug release rates, dynamic swelling behavior, and pH sensitivities of copolymers ranging in composition from 0 to 30mol% FOSA were studied. Pheniramine maleate, an ocular antihistamine, was used as the model drug substance. Hydrogels of DMA produced with increasing amounts of FOSA had a decreased equilibrium media content and exhibited a slower drug release rate. Early-time, late-time and Etters approximation drug diffusion coefficients ranged from 0.4×10−3 to 12.3×10−3mm2/min. The diffusion of the drug model was less sensitive to pH of the buffered media over the range of pH 4–8, but increasing the media pH slowed the permeability slightly by decreasing the swellability of the hydrogel. The power law exponent (n≈0.5) and the swelling interface number (Sw≫1) suggested that the drug release mechanism from these hydrogels was Fickian and not swelling controlled. These novel thermoprocessible hydrogels have potential to be used as controlled ocular drug delivery devices (e.g. contact lenses or ocular inserts).