In vivo percutaneous absorption: a key role for stratum corneum/vehicle partitioning

Summary Percutaneous absorption of five compounds was studied in the hairless rat in vivo: benzoic acid, caffeine, hydrocortisone, inulin and thiourea. The results clearly demonstrate that, as with in vitro experiments, a steady-state flux can be achieved in vivo. This steady-state flux is strongly molecule dependent. Thus, the values for inulin and benzoic acid differ by a factor of about 40. In contrast, although the physicochemical properties of the studied compounds vary widely, their lag times were not significantly different. The mean lag time was 11±2 min. Different compounds could be considered to have approximately the same apparent diffusion coefficient with regard to their percutaneous absorption in vivo. Thus, for a given thickness of stratum corneum and a given anatomical site, the penetration flux value of a substance depends only on its stratum corneum/vehicle partition coefficient. Using a classical model, we have demonstrated that the amount of substance present in the stratum corneum (Q_sc) at equilibrium (30 min) is related to this partition coefficient. There is also a linear relationship between steady-state flux and Q_sc. In practice, the in vivo steady-state flux of penetration of a compound can be predicted from the simple measurement of the amount present in the stratum corneum after a contact time of 30 min.