Hydration and percutaneous absorption.

The state of hydration of the normal stratum corneum ranks next to the nature of the penetrating molecule as the most important factor in the rate of percutaneous passage of any substance. If the stratum corneum is removed, the barrier to gain or loss of water vapor is lost. Diseased skin in which the process of keratinization is disturbed becomes more susceptible to transepidermal water loss. Diffusion through the stratum corneum is a passive process, affected only by physical factors, chiefly the water vapor pressure gradient. The low diffusion constant and high activation energy suggest that extensive hydration does not drastically affect the 'barrier' function of the stratum corneum. Below 100% ambient relative humidity, water transfers outward and a gradient in water concentration exists within the stratum corneum. The horny layer swells continuously on immersion in water, absorbing as much as ten times the dry weight. The water is bound within the intracellular keratin. Permeability increases rapidly initially and then slows down to a steady state diffusion. Regardless of the increase in permeability, the highly hydrated stratum corneum remains quite water impermeable, with a diffusional resistance ca. 10(4) times greater than an equivalent layer of water. The diffusion process is determined mainly by the intrinsically low diffusivity and the ultrastructure of the intracellular keratin.