j. Cosmet. Sc]., 53, 291-319 (September/October 2002) Papers presented at the Annual Scientific Seminar of the Society of Cosmetic Chemists May 9-10, 2002 Hyatt ReDency San Antonio San Antonio, Texas 291

292 JOURNAL OF COSMETIC SCIENCE METHODS TO ASSESS SKIN PENETRATION Thomas J. Franz, M.D. Adequate delivery of drugs and cosmetics to their site of action in the skin is essential to the development of effective products. A number of different approaches (pharmacokinetic and pharmacodynamic) to assess the penetration of topically applied materials are currently available. Each has unique characteristics to support its relevance, but all have limitations as well. This presentation will discuss the utility of several of these techniques and examine the types of data obtained in each case. 1. Human Cadaver Skin Model: This model has been widely used over the past half-century to evaluate the movement of drugs, cosmetic agents, and toxicants through the skin and its relevance as a model for living man has been well documented. Its greatest use has been in the development and screening of formulations to enhance absorption and maximize bioavailability. The model is dependent tipon the fact that the skin's barrier (stratum corneum) retains its structural integrity after death and, therefore, is suitable for in vitro evaluation. Validation of function integrity following harvesting and mounting on diffusion chambers is essential and this is accomplished by assessing water permeability through the use of tritiated water or measurement of transepidermal water loss (TEWL). Though animal skin is frequently used in this model, the relevance to man is unpredictable and examples of misleading data common. Comparison of the bioavailability of monographed drugs (hydrocortisone, hydroquinone, salicylic acid) using the cadaver skin model show large differences between marketed products. Differences in efficacy can be assumed and, in one case, can be demonstrated. 2. Stratum Comeum Tape Stripping (DPK): In recent years there has been a resurgence of interest in tape stripping as a means to directly assay the content of drugs and cosmetics in the stratum corneum, or to quantitate percutaneous absorption through analysis of the "in transit" compartment. Elegantly simple in concept, there is currently an absence of data to demonstrate concordance between experimental results and theoretical expectations. Though the method does indeed have utility, complete validation is currently lacking and, at present, it must be used with caution. 3. Transepidermal Water Loss: Assessing changes in the functional integrity of the skin's barrier can be accomplished by measuring the rate of water loss (evaporimeter), since the prime function of the stratum corneum is to serve as a water barrier. Agents that affect the skin in different ways (irritants, retinoids) can be shown to alter barrier function, and the measurement of changes in the TEWL over time can be a very sensitive means by which to assess the dynamics of these agents. 4. Gene Profiling: A technique that combines stratum corneum tape stripping with the analytical tools of molecular biology holds great promise for the future. Recovery of intact DNA and RNA from the stratum corneum offers a non-invasive, sensitive, and specific method for assessing the actions of topically applied agents on the skin. The potential for use of this new technique to address a number of issues in both dermatopharmacology and dermatotoxicology are readily apparent.