Prediction of the skin permeability of topical drugs using in silico and in vitro models

The main challenge of topically applied drugs is to overcome the skin barrier to reach the site of action at the concentration needed for efficacy. In the research of new topical drugs, design of molecules with optimized properties for skin penetration is a key factor and assays for its characterization are needed. A group of 20 representative topical molecules of clinical use were studied in two in silico models (Potts & Guy and Barratt), and an in vitro assay with artificial membrane (Skin-PAMPA). A subset of 9 drugs were also evaluated in the Franz cells assay, formulated in a solvent and in a marketed formulation. Each assay allowed us to grade compounds according to their permeability value. Globally good alignments were found for the studied compounds when comparing models, although discrepancies for some compounds such as tazarotene, tacrolimus, ketoconazole and metronidazole were observed. Overall, the studied in silico and the in vitro models are useful tools to support selection and characterization of research compounds in terms of skin permeability.