Permeation of topically applied caffeine through human skin - a comparison of in vivo and in vitro data

center dot The hair follicles represent important shunt routes into the skin for a multiplicity of drugs and chemicals. Recently, it has been shown that the hair follicles are responsible for a fast delivery of topically applied substances. After topical application, caffeine was already detected in the blood of the volunteers after 5 min, whereas, when the hair follicles were selectively blocked utilizing the newly developed Follicular Closing Technique (FCT), caffeine was detectable only after 20 min. Because of ethical reasons, in vivo investigations are not always applicable. Therefore, appropriate in vitro methods have to be developed and compared with the available in vivo data, in order to identify their transferability. WHAT THIS STUDY ADDS center dot In the present study, the FCT was adapted for in vitro use in the Franz diffusion cell and the penetration of caffeine was investigated and compared with the previously obtained in vivo data. It was shown that the combination of FCT and Franz diffusion cell represents a valuable method to estimate the follicular penetration process in vitro, which revealed comparable results in vivo, whereas the kinetics of caffeine penetration were significantly different. These findings are of importance and need to be kept in mind when evaluating the results obtained in in vitro studies. AIMS Due to ethical reasons, in vivo penetration studies are not applicable at all stages of development of new substances. Therefore, the development of appropriate in vitro methods is essential, as well as the comparison of the obtained in vivo and in vitro data, in order to identify their transferability. The aim of the present study was to investigate the follicular penetration of caffeine in vitro and to compare the data with the in vivo results determined previously under similar conditions. METHODS The Follicular Closing Technique (FCT) represents a method to investigate the follicular penetration selectively. In the present study, FCT was combined with the Franz diffusion cell in order to differentiate between follicular and intercellular penetration of caffeine into the receptor medium in vitro. Subsequently, the results were compared with the data obtained in an earlier study investigating follicular and intercellular penetration of caffeine in vivo. RESULTS The comparison of the data revealed that the in vitro experiments were valuable for the investigation of the follicular penetration pathway, which contributed in vivo as well as in vitro to approximately 50% of the total penetration, whereas the kinetics of caffeine penetration were shown to be significantly different. CONCLUSIONS The combination of FCT with the Franz diffusion cell represents a valuable method to investigate follicular penetration in vitro. Nevertheless, in vivo experiments should not be abandoned as in vitro, structural changes of skin occur and blood flow and metabolism are absent, probably accounting for reduced penetration rates in vitro.