An evaluation of structure-penetration relationships in percutaneous absorption.

Prediction of chemical transport across skin is important both to the optimization of topical and transdermal drug delivery and to the assessment of risk following dermal exposure. To facilitate estimation of percutaneous absorption, a number of model in vitro experimental systems have been developed. However, the predictive applicability of the different approaches (with respect to human skin penetration), and the quantitative aspects of the structure-permeation behavior revealed, have not been critically evaluated. The objectives of this paper are to collect, from the literature, the more systematic investigations pertaining to chemical transport across the skin, to quantify the dependence of permeation on the lipophilicity of the penetrants studied, and to assess the relative utility of model systems for the prediction of percutaneous absorption. The categories of chemicals addressed in the survey include n-alkanols, para-substituted phenols, steroids and non-steroidal anti-inflammatory drugs. The experimental systems, used in the studies considered, involve, primarily, steady-state transport measurements across excised skin taken from either human cadavers or hairless mice. Favorable comparisons of these data to solute flux across simple organic liquid membranes are possible. Overall, general patterns of behavior emerge from the analysis such that qualitative predictions can be made. From a quantitative standpoint, though, it is clear that additional "structure-activity" work is necessary to provide appropriate equations that can relate penetration between different test systems and between different chemical classes.

Pharmacokinetic considerations in the use of newer transdermal formulations.

This review addresses the pharmacokinetics and pharmacodynamics of transdermally delivered drugs. The systemic input of drugs via the skin has attracted considerable interest over the past 15 years. The early promise of the administration route has, to some extent, been realised with the approval and successful launching of transdermal formulations of hyoscine (scopolamine), glyceryl trinitrate (nitroglycerin), clonidine and oestradiol. The further application of transdermal delivery, however, will require additional effort. While other molecules (e.g. testosterone, fentanyl, nicotine) may ultimately be administered in this way, important questions pertaining to pharmacology (tolerance), toxicity (irritation, sensitisation) and dose sufficiency (penetration enhancement) remain. These problems are illustrated using information which has been published in the literature. Overall, while the enthusiasm for attraction and benefits of transdermal delivery remain evident, it is clear that future successes will demand a heightened level of commitment and skill from the pharmaceutical scientist.