Correlation between polymer properties, extrusion process parameters and permeability of etonogestrel in ethylene vinyl acetate (EVA) films.

Ethylene vinyl acetate (EVA) copolymers have been extensively used in controlled drug delivery systems due to its good biocompatibility and tunable applicability based on simple variations in vinyl acetate (VA) content. We investigated impacts of polymer properties and extrusion process parameters of EVA on permeability of etonogestrel in EVA films. Among all factors studied, the VA content was the most dominant factor that controls drug permeability by affecting crystallinity of EVA. EVA molecular weight, drawing, and cooling of EVA during extrusion process exhibited less significant effects. The impacts of these factors on crystallinity, crystallite size, and degree of crystalline orientation of EVA were characterized using polarized light microscope (PLM), differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Based on solution-diffusion model, the mechanisms by which the crystalline properties controlled drug solubility and diffusivity in EVA were discussed. These results can be applied to investigate the effects of EVA material properties and manufacturing process conditions on drug release properties of reservoir-type EVA-based drug delivery systems designed with a rate-controlling EVA membrane.