Cutaneous Absorption on RHE: Guidance to the Choice of Solvent for Topical Application

Reconstructed human epidermis (RhE) model is recognized as a possible in vitro alternative of human skin to assess cutaneous absorption. RhE is a very relevant in vitro model as it combines barrier and biological functions. For topical application, the question to ask is how to choose the vehicle for optimized cutaneous absorption.

The absorbed dose of chemical topically applied should increase linearly with concentration until the saturated concentration. This limit corresponds to the saturated concentration of chemical in the stratum corneum. It should be independent of the nature of the vehicle, as it does not modify the barrier properties of the stratum corneum. Consequently, the best vehicle is not necessarily the best solvent adapted to solubilize the chemical. On the contrary, the greater absorption could be reached using the worst solvent for chemical solubility.

Caffeine and Butylated hydroxytoluene (BHT) solubilized either in water or in corn oil were applied on Episkin® model. Kinetic experiments with infinite dose were measured, allowing measuring permeability coefficient and flux at steady state.

Caffeine solubilized in water fits with the theory, whereas BHT differs. It means that the absorbed dose still increase above the saturated concentration of BHT in water as in corn oil. Nevertheless, the absorbed amount of BHT is around twice lower with corn oil whereas the saturated concentration is almost 400 greater than with water.

Such results should defined relevant rules to choose proper solvent for topical application on RhE. Similar conclusion could be extended to any other type of skin.