Skin models for the testing of transdermal drugs

Abstract

The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro–in vivo correlation and the demonstration of bioequivalence.

Cutaneous Permeation and Penetration of Sunscreens: Formulation Strategies and In Vitro Methods

“…Indeed, both the composition and packing of stratum corneum lipids, known to be key factors of skin permeability, differ between rodent and pigskin [38].…”

Antidermatophytic Activity and Skin Retention of Clotrimazole Microemulsion and Microemulsion-Based Gel in Comparison to Conventional Cream

“…For the antidermatophytic activity study, Trichophyton mentagrophytes was selected as a model fungus since it is one of the most widespread zoophilic dermatophytes transmitted from animals to human [19,20]. For the skin penetration study, skin from naturally dead newborn pigs was used as the alternative membrane to human skin for ethical and morphological reasons [21,22].…”

Transdermal Permeation of Drugs in Various Animal Species

“…Cultured skin models have already been used in skin irritation/corrosion tests according to OECD guidelines, and also used as an alternative membrane to human and animal skins in in vitro skin permeation experiments, although they have no appendage organs, such as hair follicles and sweat ducts. A number of studies have compared epidermis (reconstructed human epidermis) and full-thickness (living skin equivalent) models with animal and human skin [8,28,34,57,71,75,76]. Schmook et al studied salicylic acid, hydrocortisone, clotrimazole, and terbinafine permeation through ex vivo human (dermatomed), porcine, rat skin, GraftSkin LSE and SkinEthic RHE [8].…”