Percutaneous Drug Penetration: Choosing Candidates for Transdermal Development

Flynn, G.L., and B. Stewart: Percutaneous drug penetration: Choosing candidates for transdermal drug development. Drug Dev. Res. 13:169-185, 1988. There is currently a high level of interest in using the skin as a route for delivering drugs. One hears the questions: What are the attributes of a drug that make it a serious candidate for transdermal delivery? By what a priori analysis might one zero in on the best transdermal candidate within a family of drugs? Answers to these questions lie in understanding the molecular factors that make a drug a facile permeant of the skin. Among other properties, it must have a high absolute affinity for the skin’s phases, which provide for its diffusive conduction. Other factors in evaluation are the potency of the drug and the relative efficiency of the drug’s systemic presentation once it has gained access to the body. One also considers the potential for the drug to elicit adverse responses in the skin. Fortunately, parallels between the drug’s ability to partition between oil and water and its ease of mass transfer across the skin can be used to ferret out a working mass transfer coefficient. If not already known, solubilities are easily experimentally deduced. The extent of first-pass metabolism by the oral route, presumed to be a known quantity, is compared with the relative amount of metabolism of the drug in the course of its diffusion through the skin, an experimentally determined quantity, in order to set the transdermal dose. These bits of information can then be used to form an early, reasonably faithful picture of the feasibility of delivering a particular drug transdermally and to make a first estimate of the size of patch required for the drug. Key wards: skin permeability, transdermal delivery, percutaneous absorption, structureactivity relationships, selecting drug candidates Received final version January 26, 1988; accepted Janaury 28, 1988. Address reprint requests to Dr. Gordon L. Flynn, College of Pharmacy, The University of Michigan, Ann Arbor. MI 48109-1065.