Predicting the Percutaneous Penetration of Cosmetic Ingredients

By: Sara Farahmand, PhD, University of Cincinnati College of Pharmacy; and Howard I. Maibach, MD, PhD, University of California School of Medicine

Posted: March 30, 2010, from the April 2010 issue of Cosmetics & Toiletries.

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The pharmacokinetic evaluation of a transdermal therapeutic system (TTS) is often accomplished through randomized crossover studies that compare either the pharmacokinetic profile of a transdermal system with that of an intravenous or oral dose or different products for bioequivalence studies. The pharmacokinetic data of transdermal patches after single dose treatment was recently summarized.⁸

Models for Permeability In relation to a material’s delivery is its penetration. Scheuplein and Blank proposed that epidermal penetration depends on the structural features of the penetrant.⁹ The epidermal transport of most solutes is restricted to passive diffusion across the stratum corneum (SC) and studies have evaluated the role of molecular structure and physicochemistry in this process. Most attempts to develop predictive equations for permeability have focused on the contributions of molecular size and the solubility in SC lipids.

The data availability and relative success in addressing the wide range of biophysical processes involved in skin permeation make molecular weight (MW) and logarithmically transformed octanol-water partition coefficient (log K_oct) the most widely used parameters for predicting skin penetration.¹ Melting point may also be considered an important predictor of skin permeability coefficient since it correlates strongly with the oil solubility of drugs.

Two types of structure-activity models have been used to estimate the skin permeability coefficients of chemicals: empirical and theoretical. Theoretical models are based on the contributions of the possible routes of percutaneous penetration and the interactions of the elements of these routes with the penetrants. Empirical models rely on the measured experimental permeability coefficients of series of chemicals and correlate them with physicochemical properties.

The Guy and Hadgraft theoretical model¹⁰ is based on a linear pharmacokinetic model. The rate constants in this model have been chosen so that they may be related to the penetrant’s physicochemical properties. Equations have been derived that may be used to estimate the concentration of drug in the plasma following transdermal application. A database of in vitro skin permeability coefficient values has been consolidated, and more than 20 empirical equations have been published estimating the permeability coefficients for chemicals penetrating the human skin from aqueous vehicles.¹