Ethanol is generally believed to be a chemical capable of enhancing drug penetration across the skin. However, the mechanism by which ethanol achieves this effect has remained unclear. We have used Attenuated Total Reflectance Infrared (ATR-IR) spectroscopy to determine the action of ethanol on human stratum corneum (skin's barrier layer) in vivo. Treatment of the skin for thirty minutes with pure ethanol liquid (a) induced a transient decrease in the intensity and frequency of the C-H asymmetric stretching vibration (which originates from the acyl chains of the intercellular lipid domains of the stratum corneum), (b) caused observable increases in spectral absorbances associated with ethanol and (c) extracted appreciable amounts of lipid from the stratum corneum. These findings contradict the suggestion that ethanol "disorders" the intercellular lipid bilayers of the stratum corneum and reveal that ethanol enters the skin and removes measurable quantities of the barrier material. The changes induced by the short contact with ethanol are reversed within 24 h. Exposure of the stratum corneum to ethanol-saturated vapor again led to detectable partitioning of the alcohol into the stratum corneum. However, while no lipid extraction would occur in this experiment, there was, once more, no evidence for the induction of lipid disordering. We conclude that ethanol's ability to enhance drug penetration across the skin is the result, at least in part, of stratum corneum intercellular lipid removal.
