Finite dose skin mass balance including the lateral part: Comparison between experiment, pharmacokinetic modeling and diffusion models

D. Selzer, T. Hahn, A. Naegel, M. Heisig, K. H. Kostka, C. M. Lehr, D. Neumann, U. F. Schaefer, Gabriel Wittum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

This work investigates in vitro finite dose skin absorption of the model compounds flufenamic acid and caffeine experimentally and mathematically. The mass balance in different skin compartments (donor, stratum corneum (SC), deeper skin layers (DSL), lateral skin parts and acceptor) is analyzed as a function of time. For both substances high amounts were found in the lateral skin compartment after 6 h of incubation, which emphasizes not to elide these parts in the modeling. Here, three different mathematical models were investigated and tested with the experimental data: a pharmacokinetic model (PK), a detailed microscopic two-dimensional diffusion model (MICRO) and a macroscopic homogenized diffusion model (MACRO). While the PK model was fitted to the experimental data, the MICRO and the MACRO models employed input parameters derived from infinite dose studies to predict the underlying diffusion process. All models could satisfyingly predict or describe the experimental data. The PK model and MACRO model also feature the lateral parts.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalJournal of Controlled Release
Volume165
Issue number2
DOIs
StatePublished - Jan 28 2013

Keywords

  • Homogenized diffusion model
  • Mathematical modeling
  • Prediction mass profiles
  • Skin absorption
  • Skin penetration

ASJC Scopus subject areas

  • Pharmaceutical Science

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