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A model is presented for transdermal drug delivery from single-layered silicone matrix systems. The work is based on our previous results that, in particular, extend the well-known Higuchi model. Recently, we have introduced a numerical transient model describing matrix systems where the drug dissolution can be non-instantaneous. Furthermore, our model can describe complex interactions within a multi-layered matrix and the matrix to skin boundary. The power of the modelling approach presented here is further illustrated by allowing the possibility of a donor solution. The model is validated by a comparison with experimental data, as well as validating the parameter values against each other, using various configurations with donor solution, silicone matrix and skin. Our results show that the model is a good approximation to real multi-layered delivery systems. The model offers the ability of comparing drug release for ibuprofen and diclofenac, which cannot be analysed by the Higuchi model because the dissolution in the latter case turns out to be limited. The experiments and numerical model outlined in this study could also be adjusted to more general formulations, which enhances the utility of the numerical model as a design tool for the development of drug-loaded matrices for trans-membrane and transdermal delivery., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)