No abstract

As a means of determining the risk of absorption of water contaminative phenolic compounds through the skin, the permeation of a number of phenols, all on the U.S. Environmental Protection Agency's list of priority pollutants, through hairless mouse skin has been studied, using in vitro diffusion cell methods. Experimentally determined permeability coefficients through intact skin and stratum corneum denuded skin and permeability coefficients derived therefrom for the viable tissue layer and the stratum corneum, which are the tissue's major contributing substrata, have been correlated with their log Koctanol/wate r partition coefficients. Permeability coefficients for the whole skin and the stratum corneum systematically increased with increasing phenol lipophilicity to limiting values of about 0.15 and 0.30 cm/hr, respectively. The values of the permeability coefficients for the viable tissue were roughly the same for all compounds (~0.36 cm/hr). Because of the inductive effects of C1 and NO 2 substituents on the aromatic ring, phenolic analogs containing these moieties are acidic and, consequently, their overall skin permeabilities were highly pH-dependent in the range of pH values seen for surface waters. High fluxes were noted for such phenols at low pH, where they exist essentially in a non-ionized state.

The advantages of delivering drugs across the skin for systemic therapy are well documented (1-6), and transdermal drug delivery, on its own merits, has now become one of the fastest growing areas in drug development. The limitations and constraints of this mode of drug therapy have to be understood, however. This present article addresses such limitations and discusses the controversies surrounding these therapeutic systems. This is attempted with the hope that a good understanding and a rational approach to developing these systems will aid in early resolution of the problem(s).Under pressure from their marketing departments, pharmaceutical companies are moving hastily to produce transdermal devices. Only with well-planned development programs that take a careful and cautious approach, transdermal technology is expected to make a significant impact on the quality of patient care. BACKGROUNDTransdermal therapeutic systems are self-contained, discrete dosage forms which, when applied to intact skin, deliver the drug(s) through the skin at a controlled rate to the systemic circulation. Systems typically comprise an outer covering (barrier), a drug reservoir which may have a ratecontrolling membrane, a contact adhesive applied to some or all 183 Copyright 0 1988 by Marcel Dekker, Inc. Drug Dev Ind Pharm Downloaded from informahealthcare.com by University of Otago on 07/19/15 For personal use only.