[In vitro methods of transdermal drug absorption: the skin PAMPA model]

The present article summarizes the features of human skin as absorption site and describes a new model for skin penetration prediction. The parallel artificial membrane permeability assay (PAMPA), a high throughput method that serves as the basis of the model is also discussed in details demonstrating its features and published applications. The paper focuses on the steps of model development and on the comparisons to human skin datasets. The one dataset by J. Hadgraft and R. Guy, containing over 100 compounds, was divided into groups corresponding to similar experimental conditions (e.g. skin type and temperature) and drug-likeness. Skin PAMPA results correlate supremely with Franz cell results measured on full thickness skin at 37 degrees C (R2=0.89). The other dataset reported by Lee et al. contains experiments with 40 compounds (27 of it is drug-like) on dermatomed skin at 32 degrees C. The Skin PAMPA permeability results show a high correlation (R2=0.84;) with it if similar experimental conditions have been applied. Intra- and inter-laboratory reproducibility has been also proved and homogeneity has been examined. The developed Skin PAMPA model is able to predict human skin permeability reasonably well, and because of its good reproducibility and 96-well based format it can be a cost effective alternative to Franz cell studies for early skin penetration prediction.