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.

Until the early 1960s, theory suggested that cosmetic ingredients rarely penetrated the skin. However, many experts today suspect that penetration occurs with most ingredients. As consumers and health care professionals have become educated about safety, the percutaneous penetration of cosmetic and fragrance ingredients has gained interest. Therefore, the industry has sought means to estimate the penetration of chemical structures through human skin.

While previous algorithms for predicting the skin absorption of permeants was based on in vitro data, the present article proposes a quantitative structure-activity relationship (QSAR) model based on in vivo human data. Here, a set of human in vivo data is described that provides entry into predicting the penetration of cosmetic ingredients.

Assessing Delivery
Due to skin barrier properties, a chemical must exhibit specific physicochemical traits in order to be a candidate for passive transdermal delivery. For example, its molecules should be small (MW < 500) and have a low melting point (< 200°C).1 However, detailed analysis of the pharmacokinetics of transdermal drug delivery and its correlation with physicochemical characteristics of the delivered drugs is minimal. Predictive equations for skin permeability coefficients of chemicals are made based on in vitro static cell experiments using animal or human skin.^{2, 3} Moreover, there is considerable interindividual variation in transdermal penetration and pharmacokinetics,⁴ which could be one reason for imprecision in predicting dermatopharmacokinetic parameters of transdermally delivered drugs based on their molecular properties.

Therefore, the dermatopharmacokinetic parameters of transdermal drugs are reviewed here. In addition, the interindividual variations in pharmacokinetic parameters such as maximal plasma concentration (Cmax) are assessed and the in vivo data and physicochemical characteristics of the drugs are correlated. For the present work, patches were chosen since they minimize variance by removing three forces that affect penetration: rub-off, exfoliation and wash.⁵

Pharmacokinetic Parameters for Delivery
The single dose pharmacokinetic profile for transdermal delivery includes three periods: the time until plasma concentrations are achieved (the lag time), the plateau at constant steady-state plasma concentrations and a declining phase, post-patch removal. The last phase may be prolonged due to a drug’s pharmacokinetic characteristics and the presence of a skin depot, where chemicals remain in the skin after the delivery system is removed; these materials may therefore enter the circulation.^{6, 7}