Small, polar compounds, both ionic and uncharged, partition into human stratum corneum immersed in aqueous solutions to an extent comparable to the water volume fraction of the tissue, then desorb in two phases. The fast phase has a time constant on the order of a few minutes, whereas the slow phase occurs over many hours. A physical model for this behavior involving a combination of tranverse diffusion through the tissue and lateral diffusion and exchange with skin appendages is presented. This concept is probed using excised human stratum corneum exposed to aqueous solutions of radiolabeled sodium chloride, tetraethyl ammonium bromide and mannitol, plus previously published data on six other compounds of varying molecular size and polarity. The fast phase desorption process becomes unimportant for lipophilic compounds. Slow phase desorption rates are size-selective, with larger species desorbing much more slowly than smaller ones. Interpreting the size-selectivity in terms of smooth cylindrical pores using the centerline approximation leads to an optimum pore radius of about 8–12 Å, depending on the model chosen.Graphical abstract
Transport of hydrophilic compounds in the stratum corneum is linked to both transcellular transport and appendageal diffusion, according to our hypothesis.