Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

An appreciation of solute-vehicle-skin interactions underpins our current understanding of the processes of percutaneous absorption as well as in the prediction of the extent of absorption. This understanding has been reached through principles developed and validated over the last century through the work of a number of authors, including Dale Wurster, Takeru Higuchi, Irvin Blank, Robert Scheuplein, Gordon Flynn, Boyd Poulsen and Tom Franz, as well as by many scientists from my and younger generations. Their work has led to an appreciation of the rate-limiting steps in percutaneous penetration, the role played by the physicochemical properties of the solute, vehicle and skin and the variability that may arise from using various experimental/mathematical/pharmacokinetic models to quantify absorption as well as enabling the prediction of local and systemic efficacy and toxicity. In addition, unexpected behaviour may result from non-ideality in solute-vehicle-skin effects, including dehydration, chemical enhancement, supersaturation, metabolism, sequestration and vascular effects, including those of nanosystems on the local vasculature. In general, in vitro skin penetration profiles are predictive of in vivo profiles but a number of exceptions also exist.