The intercellular lipids in the stratum corneum form structures composed of ordered phases with orthorhombic and hexagonal hydrocarbon-chain packing structures and, in addition, a structure composed of a disordered fluid phase. Although the fluid phase plays an important role in percutaneous penetration, little attention has been paid to it in the literature thus far. Recently, a method to estimate the proportion of the fluid phase within the lipids of the stratum corneum was proposed and it was shown to reach about 80%. However, since that study assumed uniform extraction of the intercellular lipids from the stratum corneum, the analysis might give rise to an overestimation of the proportion of the lipids in the fluid phase. We developed a way to investigate the proportion of the lipids in the fluid phase by treating with ethanol, into which the lipids in the fluid phase might be dominantly dissolved. From the experiment we pointed out the possibility that the proportion of the lipids in the fluid phase reached more than 50% of the whole intercellular lipids. Therefore, the fluid-phase region in the intercellular lipid matrix should be taken into account when considering the percutaneous penetration mechanism.
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