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Pig Ear Skin ex Vivo as a Model for in Vivo Dermatopharmacokinetic Studies in Man

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Objective

The objective was to investigate pig ear skin as a surrogate for human skin in the assessment of topical drug bioavailability by sequential tape-stripping of the stratum corneum (SC). The potential benefits of ex vivo investigations are manifold: ethical approval is not required, multiple replicate experiments are more easily performed, and toxic compounds can be evaluated.

Materials and Methods

Ex vivo experiments on isolated pig ears were compared with in vivo studies in human volunteers. Four formulations, comprising the model drug, ibuprofen, in different propylene glycol (PG)-water mixtures (25:75, 50:50, 75:25 and 100:0), were compared.

Results

Derived dermatopharmacokinetic parameters characterizing the diffusion and partitioning of the drug in the SC ex vivo were consistent with those in vivo following a 30-minute application period. Further, the non-steady-state ex vivo results could be used to predict the in vivo concentration profile of the drug across the SC when a formulation was administered for 3 h (i.e., close to steady-state).

Conclusions

Taken together, the results obtained suggest that pig ear skin ex vivo has promise as a tool for topical formulation evaluation and optimization.

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Acknowledgments

We thank Leo Pharmaceutical Products (Denmark) for financial support. We are indebted to the following individuals for stimulating discussion, suggestions, comments and criticism of the work performed: Drs. A. Jorgensen, E. Didriksen, A. Fullerton, V. Shah and, in particular, Professor Annette Bunge from the Colorado School of Mines (Golden, CO, USA).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, University of Geneva, 30 quai E. Ansermet, CH-1211, Geneva 4, Switzerland

    Christophe Herkenne, Aarti Naik, Yogeshvar N. Kalia & Richard H. Guy

  2. Centre Pharmapeptides, Parc d'affaires International, F-74160, Archamps, France

    Christophe Herkenne, Aarti Naik & Yogeshvar N. Kalia

  3. The School of Pharmacy, University of London, 29/39 Brunswick Square, London, WC1N 1AX, UK

    Jonathan Hadgraft

  4. Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    Richard H. Guy

Authors
  1. Christophe Herkenne
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  2. Aarti Naik
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  3. Yogeshvar N. Kalia
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  4. Jonathan Hadgraft
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  5. Richard H. Guy
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Correspondence to Richard H. Guy.

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Herkenne, C., Naik, A., Kalia, Y.N. et al. Pig Ear Skin ex Vivo as a Model for in Vivo Dermatopharmacokinetic Studies in Man. Pharm Res 23, 1850–1856 (2006). https://doi.org/10.1007/s11095-006-9011-8

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  • DOI: https://doi.org/10.1007/s11095-006-9011-8

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