Mathematical modelling of the release of drug from porous, nonswelling transdermal drug-delivery devices.

A general model is presented for the release of drug from porous nonswelling, transdermal drug-delivery devices and it is shown to reduce to previously proposed models in suitable limits. The processes which govern the release of drug are considered to be diffusion of dissolved drug and dissolution of dispersed drug, both in the body of the device and in the device pores, and transfer of drug between the two domains. In the classical limit of large dissolution rates, the problem reduces to one of the moving-boundary type, and solution of this problem in the case where the initial drug loading is much greater than the drug solubility in the device yields expressions for the flux of drug to a perfect sink (modelling in vitro conditions). It is shown that behaviour greatly differing from the classical first-order drug delivery (alpha t 1/2) may be exhibited, depending upon the parameter regime. In some situations the dissolution rates may not be so large and solutions of the general model are derived in the case where the dispersed drug is considered to be undepleted and the diffusivity in the solvent-filled pores is much larger than in the body of the delivery device. Numerical studies are undertaken, and the coupling of delivery device and skin-diffusion models (in order to model the complete transdermal drug-delivery process) is also considered.