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Qualitative and quantitative comparison of heat separated epidermis and dermatomed skin in percutaneous absorption studies
Authors:Nicolas Atrux-Tallau  Fabrice Pirot  Françoise Falson  Michael S. Roberts  Howard I. Maibach
Affiliation:(1) Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, Faculté de Pharmacie, EA 4169, Fonctions normales et pathologiques de la barrière cutanée, 8, Avenue Rockefeller, Université Lyon 1, 69373 Lyon cedex 08, France;(2) Therapeutics Research Unit, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD, 4102, Australia;(3) Department of Dermatology, University of California, San Francisco, CA 94142-0989, USA
Abstract:Transepidermal water loss (TEWL), mainly regulated by the stratum corneum, was quantitatively correlated to percutaneous absorption of compounds in human and suggested for the ex vivo assessment of skin integrity. The present study investigated qualitatively and quantitatively the relevance of 100-μm heat separated epidermis (HSE) in percutaneous absorption studies as compared to 500-μm dermatomed skin by dual complementary approaches. Percutaneous absorption of caffeine delivered from aqueous solution through dermatomed skin or HSE specimens (n = 9) was measured using vertical static diffusion cells coupled with an unventilated evaporimeter enabling the assessment of TEWL and skin integrity for 21 h. Permeation of caffeine exhibited different finite dose-like profiles ranged according to the thickness of skin specimens (cumulative dose absorbed up to 21 h: 11.5 ± 11.5 μg/cm2 and 29.4 ± 36.2 μg/cm2 through dermatomed skin and HSE, respectively). Normalized TEWL and caffeine fluxes were similar through dermatomed skin and HSE suggesting that the intrinsic permeability properties of both models were undifferentiated over time. Interestingly, a significant relationship was shown between TEWL and caffeine fluxes, suggesting the usefulness of TEWL measurement as an element in the estimation of percutaneous drug absorption. In conclusion, the present showed that percutaneous absorption through HSE was qualitatively and quantitatively similar to dermatomed skin when TEWL as endogenous standard and skin thickness were considered in permeability data comparisons.
Keywords:Heat separated epidermis  Dermatomed skin  Caffeine  Transepidermal water loss  Skin permeability
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