In vivo methods for percutaneous absorption measurements

Abstract

There is a persistent belief that skin viability has little importance in percutaneous absorption. This concept of skin as a passive membrane has led to the domination of the study of percutaneous absorption by laws of mass action and physical diffusion. This concept has also led investigators to use skin excised from cadavers (human and animal) and then to physically (e.g., by freezing or heat separation) and chemically isolate skin sheets or sections and determine chemical diffusion across these treated tissues. A recent study shows that these methods destroy skin viability (1). Human skin viability currently can be maintained for up to a week under the proper conditions. A consequence of this earlier concept was the designation of the stratum corneum as the barrier to percutaneous absorption. Many compounds such as low-molecular-weight alcohols were studied, and the barrier properties of the isolated stratum corneum were demonstrated for these chemicals. It has then been assumed that the stratum corneum is the primary barrier for all compounds. The need to study percutaneous absorption has its reality in dermatotoxicity, by which compounds pose a threat to human health, and in dermatopharmacology, for which drugs need to be delivered into and through the skin to treat disease both locally (skin disease) and systemically (transdermal delivery). Most compounds and defined drugs that are of interest and concern in dermatotoxicology and dermatopharmacology are lipophilic.