Pig ear skin ex vivo as a model for in vivo dermatopharmacokinetic studies in man

Pharm Res. 2006 Aug;23(8):1850-6. doi: 10.1007/s11095-006-9011-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Data Interpretation, Statistical
  • Diffusion
  • Diffusion Chambers, Culture
  • Ear, External / metabolism*
  • Female
  • Humans
  • Ibuprofen / administration & dosage
  • Ibuprofen / pharmacokinetics
  • In Vitro Techniques
  • Kinetics
  • Male
  • Middle Aged
  • Propylene Glycols / chemistry
  • Skin Absorption / physiology*
  • Swine

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Propylene Glycols
  • Ibuprofen