Reconstructed epidermis and full-thickness skin for absorption testing: influence of the vehicles used on steroid permeation.
A protocol for percutaneous absorption studies has been validated, based on the use of reconstructed human epidermis (RHE) and aqueous solutions of test substances. However, it is often the case that it is more-complex formulations of drugs or chemicals which will make contact with the skin surface. To investigate whether RHE and the reconstructed full-thickness skin model (FT-model) can be used to predict uptake from formulations, we compared the permeation of hydrocortisone and testosterone when applied in emulsion form and as a solution containing the penetration enhancer, ethanol. Human and pig skin and a non-cornified alveolar model served as references. The results were compared with steroid release from the formulations. The permeation rates of the steroids were ranked as: alveolar model >> RHE > FT-model, pig skin > human skin. In accordance with the rapid hydrocortisone release from the formulations, the permeation rates of this steroid exceeded those of testosterone. Only minor differences were observed when comparing the testosterone formulations, in terms of release and permeation. However, the ranking of the permeation of the hydrocortisone formulations was: solution > w/o emulsion > o/w emulsion, which permitted the elucidation of penetration enhancing effects, which is not possible with drug release studies. Differences in penetration were most obvious with native skin and reconstructed tissues, which exhibited a well-developed penetration barrier. In conclusion, RHE and skin preparations may be useful in the development of topical dermatics, and in the framework of hazard analysis of toxic compounds and their various formulations.
Schäfer-Korting
Monika
M
Freie Universtät Berlin, Institut für Pharmazie (Pharmakologie & Toxikologie), Königin-Luise-Strasse 2-4, Berlin, Germany. msk@zedat.fu-berlin.de
Mahmoud
Ashraf
A
Lombardi Borgia
Simone
S
Brüggener
Barbara
B
Kleuser
Burkhard
B
Schreiber
Sylvia
S
Mehnert
Wolfgang
W
D000328:Adult; D000728:Androgens / Q000493:pharmacokinetics; D000826:Animal Testing Alternatives / Q000592:standards*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics; D004655:Emulsions; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000493:pharmacokinetics; D008875:Middle Aged; D014677:Pharmaceutical Vehicles / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013256:Steroids / Q000493:pharmacokinetics*; D013552:Swine; D013739:Testosterone / Q000493:pharmacokinetics
D000728:Androgens; D000893:Anti-Inflammatory Agents; D004655:Emulsions; D014677:Pharmaceutical Vehicles; D013256:Steroids; D000431:Ethanol; D013739:Testosterone; D006854:Hydrocortisone