Percutaneous absorption: a single-layer model.

Abstract

In vitro percutaneous permeation of betamethasone 17-valerate through excised human skin was studied. Pressure-sensitive silicone adhesive containing betamethasone 17-valerate in suspension was used as a vehicle. Steady-state flux through the split-thickness skin was similar to that through the isolated epidermis. However, the lag-time and half-life after removal of the vehicle were longer for the split-thickness skin than from epidermis. At steady state, 37% of the drug in the split-thickness skin was partitioned in dermis. When the kinetic parameters of a simple single-layer model are defined to specify the permeability coefficient and the drug amount in skin at steady state, this model can predict the longer half-life observed for the split-thickness skin sample compared with that for epidermis. The difference between the observed and theoretical values of the half-life after removal of the vehicle was within 23%. On the other hand, the lag-time had a large variation and the simple diffusion model failed to be predictive. A single-layer model described by two or three kinetic parameters may be able to describe percutaneous permeation kinetics even when the processes after the compound permeation through stratum corneum are not negligible. However, it is stressed that none of the kinetic parameters inherent in this simple model directly represents one of the single physicochemical parameters, such as diffusion and partition coefficients and path length of each skin layer.