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‘Soak and smear’ method, water soaking to induce skin hydration followed by topical corticoids application suggests effectiveness in clinical dermatological practice. We investigate one possible mechanism of soaking times effect on drug partitioning and diffusion rates in skin and its proposed efficacy. Utilizing an  in vitro  flow-through diffusion system to evaluate efficacy of the ‘soak and smear’ method following 0.5, 8, and 20 min water soaking and [ 14 C]-hydrocortisone topical application on human skin to probe the possibility of percutaneous penetration enhancement. In water-soak groups, more [ 14 C]-hydrocortisone was absorbed and retained in stratum corneum and epidermis, whereas, in the control (no soak) more was in the deep skin–dermis and receptor fluid. These differences between water-soak groups and the control are statistically significant ( p  &lt; .05). Effect of ‘soak and smear’ on skin absorption and penetration depends on interaction of individual drug’s physicochemical property, stratum corneum hydration, and stratum corneum–epidermoid barrier status. Water soaking (20 min) induced skin hydration increases [ 14 C]-hydrocortisone absorption and retention into the upper skin layer but not deep layers. This could support the proposed hypothesis of clinical dermatological treatment of hydrocortisone to local skin inflammations should the epidermis be found to be a key target for atopic dermatitis therapy.

Effect of soak and smear on [14C]-hydrocortisone in vitro human skin percutaneous penetration