Vehicle effects on percutaneous absorption: in vivo and in vitro comparisons with human skin

The percutaneous absorption of benzoic acid, caffeine and testosterone through human skin was measured by using in vivo and in vitro techniques. The compounds were applied to the skin in solution in three vehicles: petrolatum, ethylene glycol gel and water gel. Because benzoic acid was ionized at the neutral pH of the gels, these data were difficult to interpret and are not reported. The stratum corneum/vehicle partition coefficients (Km) and percent saturation of the vehicles with substrate were determined to aid in the interpretation of the absorption results. In the in vitro studies, the permeability constants determined for the compounds in each vehicle correlated with either the Km value or the percent saturation of the vehicle. Caffeine penetrated most readily from a petrolatum vehicle, and the greatest testosterone absorption was from a water gel. Permeation was also expressed in terms of the percentage of the applied dose absorbed. Reasonable agreement was obtained between the in vivo and in vitro values. Although no significant differences occurred between most values compared, there was a trend toward lower penetration in the in vitro system.