Intrinsic diffusion coefficients of drugs in pressure-sensitive adhesive polymer masses

Abstract

The determination of diffusion coefficients in pressure-sensitive adhesive polymers is a prerequisite to evaluate suitable adhesive polymers for transdermal patches. This paper reports on a membrane permeation technique through laminates composed of a pressure-sensitive adhesive layer and a microporous membrane for mechanical support, allowing easy handling of the adhesive without problems due to sticking. In order to determine intrinsic diffusion coefficents, the effects of the adjacent aqueous diffusion layers and of the microporous membrane were factored out by simultaneous data analysis of different adhesive layer thicknesses. To standardize the drug's thermodynamic activity, all experiments were carried out with saturated drug dispersions. The drugs investigated were three verapamil analogs, i.e. gallopamil, anipamil, and the verapamil carboxylic acid analog. To illustrate the method, experiments with different pressure-sensitive adhesives were carried out in which the effects of drug and polymer structure on diffusivity were clearly demonstrated. The effects of cross-linking, of polar and non-polar additives, and of initial drug loading were also studied, resulting in moderate or negligible effects on drug diffusivity. In agreement with theory, it was finally demonstrated that the contribution of the aqueous diffusion layers to the overall permeability of the laminates was significant when highly permeable adhesives were studied.