Issue 43 — December 2007

Issue 43
Category		Title		Author
Congress Report		Percutaneous absorption: Proof of evidence and models		Wolfgang Pittermann

A question frequently asked in cosmetics which, among other things, was discussed at an educational meeting organized by the Swiss Society of Cosmetic Chemists relates to the penetration depth of active ingredients applied on the skin. A frequently given reply to this question is that many cosmetic substances "get stuck" in the uppermost skin layer and that the penetration depth of active ingredients is dependent on the kind of substance used. It would be preferable to reply that the penetration depth of active ingredients is dependent on the formulation and on the detection method used and that it is not fully known what really "gets stuck" (after repeated application).

The skin is the largest organ of the human body. If we, however, compare the amount of findings on the penetration of certain ingredients or active substances with penetration data of the gastro-intestinal tract for instance, some questions remain unanswered in relationship to the size of the skin as an organ. The above mentioned simple reply may thus be regarded as dissatisfying.

Methods and formulations for strategies for improved skin penetration are described and discussed in literature in detail (1). The impression arises that it is generally possible to give a proof of evidence. Yet, the penetration of cosmetic or dermatological formulations through the natural barrier of the horny layer is dependent on a combination of physiological and physical effects. Such results cannot be obtained by applying physical methods alone.

The main difficulty is given by the multiple layers of the skin, and the skin in itself, which is a living, very dynamic, growing biomembrane, and which additionally is closely associated with psychic factors. The most important factors influencing the permeability of active ingredients are the barrier and reservoir functions of the horny layer. The barrier and reservoir functions are characterized in a special way: With growing depth, the barrier function increases whereas its function to form a reservoir for topically applied substances decreases. In the original and in the model, the barrier and reservoir functions fulfill their tasks through an interplay with an adequate dermal receptor situation underneath the horny layer/ epidermis. Under natural conditions, this mainly concerns the blood vessel systems and, to a minor degree, the lymph vessels. The subpapillary capillar network also shows particular organ-specific properties, namely partly fenestrated vessel walls. They display a higher "leakage" for the absorption of foreign substances than the remaining organism.

A transportation of active ingredients is possible via the appendages of the skin, or through the epidermis. Under the aspect of providing an up-to-date proof of efficiency, both the penetration into sebaceous glands and hair follicles (root of hair) and the transepidermal route leading to the connective tissue of the dermis are of interest.

The following illustration shows various routes which a substance may take to penetrate the skin's barrier.

Illustration: Possible pathways for a penetrant to cross the skin barrier. (1) across the intact horny layer, (2) through the hair follicles with the associated sebaceaous glands, or (3) via the sweat glands (Figure 3, Rolf Daniels, Strategies for Skin Penetration Enhancement, Skin Care Forum 37, www.scf-online.com)

For penetration studies, various methods and models are available, such as microdialysis, the perfused bovine udder skin model (BUS) or the Franz Diffusion Chamber. There, the barrier and receptor arrangements differ largely, and therefore the models are applicable in various ways. With the formulation concepts which have been developed in the past few years and which are based on microemulsions or nanodispersing vehicle systems, new and high demands on the model situations arise. An improvement of the physical penetration of substances is made possible by iontophoresis, for example.

Further details on the subject of percutaneous absorption in the context of human skin models are given in a dissertation (2). The demand for alternative test methods in the safety assessment of cosmetics, chemicals and pharmaceuticals have been included in the EU directives. Alternative methods for the determination of percutaneous absorption are targeted at reducing or replacing the use of animals and to achieve a more reliable in vivo prediction of the response in human skin than in animal tests.

Remarks:

Dr. Wolfgang Pittermann gave a special paper on the topic "Percutane Absorption: Nachweise und Modelle" at the SWISS SCC, Fortbildungsveranstaltung, (Olten, October 2006).

Also see: Die Schweizer Kosmetika- und Parfum-Industrie, SWISS SCC Fortbildungsveranstaltung October 19, 2006, Olten, Switzerland: Wirksamkeit und Sicherheit - ein eingespieltes Team, ed. Marion Fröschle, EUROCOSMETICS 1-2007, 30-33.

References:

(1) Rolf Daniels, Strategien zur Verbesserung der Hautpenetration, Skin Care Forum 37, www.scf-online.com.

(2) Sylvia Schreiber, Charakterisierung humaner Hautmodelle - Stabilität und metabolische Kapazität sowie vergleichende Untersuchungen zur perkutanen Absorption, Dissertation, FB Biologie, Chemie, Pharmazie, Freie Universität Berlin, Berlin 2006.