International Journal of Pharmaceutics, 64 (1990) 117-126 Elsevier 117 IJP 02139 Intrinsic diffusion coefficients of drugs in pressure-sensitive adhesive polymer masses Rainer Lichtenberger * and Hans P. Merkle + Pharmazeutisches Institut, Pharmazeutische Technologie, Universitzit Bonn, An der Immenburg 4, D-5300 Bonn I (F.R.G.) Received I8 December 1989) (Modified version received 24 March 1990) (Accepted 27 March 1990) Key words: Pressure-sensitive adhesive, Intrinsic diffusion coefficient; Laminate permeation; Transdermal patch; Verapamil analog; Gallopamil; Anipamil 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 membr~e were factored out by simultaneous data analysis of different adhesive layer thicknesses. To standardize the drug’s the~~yn~c 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. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Introduction The diffusion coefficient has become a com- mon parameter for the evaluation of polymeric materials for drug delivery. Standard approaches + Correspondence (present address]: HP. Merkle, Department of Pharmacy, Swiss Federal Institute of Technology Zihich, ETH-Zentrum, CH-8092 Ztirich, Switzerland. * Present address: E. Merck Pharmaceutical Department, For- mulations Research, Frankfurter Str. 250, D-6100 Darmstadt, F.R.G. to determine diffusion coefficients are membrane permeation and matrix release techniques. With pressure-sensitive adhesive polymers, however, simple membrane permeation experiments are technically unfeasible: Most pressure-sensitive ad- hesive polymers do not form self-supporting films, and due to their adherence to substrates such films would be difficult to handle as free mem- brane in a donor/receiver permeation experiment. Matrix release tectiques, on the other hand, pro- vide effective rather than intrinsic diffusion coeffi- cients as the degree of saturation and interaction of the drug in the polymeric matrix is normally 0378-5173/90/~03.50 D 1990 Etsevier Science Publishers B.V. (Biomedical Division)