MATHEMATICAL-MODELING OF THE RELEASE OF DRUG FROM POROUS, NONSWELLINGTRANSDERMAL DRUG-DELIVERY DEVICES

A general model is presented for the release of drug from porous nonsw elling, transdermal drug-delivery devices and it is shown to reduce to previously proposed models in suitable limits. The processes which go vern the release of drug are considered to be diffusion of dissolved d rug 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 reduce s 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 behavio ur greatly differing from the classical first-order drug delivery (pro portional to t(1/2)) may be exhibited, depending upon the parameter re gime. In some situations the dissolution rates may not be so large and solutions of the general model are derived in the case where the disp ersed drug is considered to be undepleted and the diffusivity in the s olvent-filled pores is much larger than in the body of the delivery de vice. Numerical studies are undertaken, and the coupling of delivery d evice and skin-diffusion models (in order to model the complete transd ermal drug-delivery process) is also considered.