Mechanism of percutaneous absorption. IV. Penetration of nonelectrolytes (alcohols) from aqueous solutions and from pure liquids.

Most quantitative permeability data on human skin are based on studies in which water was used as the vehicle. Very little is known of the permeability of normal stratum corneum as it exists in vivo where it is considerably less hydrated. Similarly very little is known of the effect of nonaqueous solvents on the skin although they are common vehicles in topical therapy. In this study the permeation rates of a homologous series of primary alcohols (C 1 -C 10 ) through skin were measured. The alcohols were applied from aqueous solutions and also as the pure liquids. The permeation behavior in the two cases is compared in terms of (1) the transport rates of the alcohols, (2) the distribution equilibrium between the tissue and vehicle, and (3) the damage to the tissue produced by the vehicle. Fick's law was found to hold as an approximation for both the aqueous and the liquid alcohol systems. Using the measured data, which include permeability and diffusion constants and tissue:vehicle partition coefficients, the diffusional resistance offered by epidermis and dermis is accurately apportioned. The overwhelming role of the stratum corneum in both the aqueous and the pure liquid systems is quantitatively confirmed. The effect of the solubility characteristics of different vehicles on skin permeability is discussed. It is shown that with the aid of a few simple principles and a knowledge of the solubility character of the vehicle, the permeation of different substances can be qualitatively predicted.