In vitro percutaneous permeation of betamethasone and betamethasone 17-valerate.

The percutaneous permeation and sorption isotherm (equilibrium) profiles of betamethasone and betamethasone 17-valerate were estimated in an in vitro study with excised human skin. Corticosteroids were measured by HPLC. The stratum corneum (dry weight)/water partition coefficient of betamethasone 17-valerate was 20 times greater than that of betamethasone. Nevertheless, when aqueous saturation was maintained in the donor solution, the mean steady-state flux of betamethasone 17-valerate through split-thickness skin was 57.6 ng/cm2/h, whereas that of betamethasone was 15.2 ng/cm2/h. This was presumably because the aqueous saturation concentration of betamethasone (60 micrograms/mL) was 11 times greater than that of betamethasone 17-valerate (5.4 micrograms/mL), so that the calculated saturation concentrations of the two corticosteroids in stratum corneum were within a factor of 2. However, the drug amounts or concentrations of the more lipophilic corticosteroid (betamethasone 17-valerate) attained in viable layers (viable epidermis and dermis) at steady state were predicted to be greater than those of the less lipophilic corticosteroid (betamethasone) when the results in the permeation and equilibrium studies were interpreted by a mathematical model. The drug distribution pattern predicted (i.e., that a more lipophilic corticosteroid preferentially partitions into viable layers) was reasonable when compared with that observed in the permeation study. The mean drug amount of betamethasone 17-valerate in dermis was four times greater than that of betamethasone, whereas the drug amounts of both corticosteroids in epidermis were similar to each other.