Measurement and prediction of the rate and extent of drug delivery into and through the skin.

Skin diseases are prevalent and can significantly affect quality of life. Empirical mathematical models retrospectively analyse data to predict skin permeation from the physico-chemical properties of drugs. Quantitative structure permeability relationships are discussed, along with alternatives to linear modelling. Mechanistic mathematical models derived from first principles are also considered. Further, in vitro experiments allow predictions to be made using suitable membranes (cultured cell lines or excised skins). In vivo methods to assess (trans)dermal drug delivery aim to minimise clinical studies, especially to determine whether formulations are bioequivalent. Microdialysis is discussed, together with the FDA-approved skin blanching (pharmacodynamic) assay for corticosteroids. The progress made with the tape stripping methodology is reviewed. Two distinct strategies have emerged, the first where the total amount of drug in the stratum corneum (SC) at one uptake and one clearance time are compared; and the second which generates drug permeation profiles across the SC, and allows dermatopharmacokinetic parameters to be derived.