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A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
Published on: February 23, 2018
A multiphase microscopic diffusion model for stratum corneum permeability. II. Estimation of physicochemical
Tsuo-Feng Wang1, Gerald B Kasting, Johannes M Nitsche
1Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260-4200, USA.
Journal of Pharmaceutical Sciences
|September 19, 2007
Summary
This study refines the stratum corneum (SC) microtransport model, finding that transcellular pathways largely govern compound permeation, irrespective of lipophilicity. The improved model better predicts skin hydration and transient permeation profiles.
Area of Science:
- Biophysics
- Pharmacokinetics
- Materials Science
Background:
- Previous work established a biphasic microtransport model for the stratum corneum (SC).
- Accurate modeling of skin permeation is crucial for drug delivery and toxicology.
- Existing models often struggle with predicting transient permeation and hydration effects.
Purpose of the Study:
- To fully parameterize the SC biphasic microtransport model using transport theory and existing data.
- To investigate the dominant pathway for compound permeation through the SC.
- To improve the prediction of skin hydration and transient permeation profiles.
Main Methods:
- Developed four microscopic transport properties (D(cor), K(cor/w), D(lip), K(lip/w)) from independent sources.
- Derived the mass transfer coefficient for transbilayer hopping (k(trans)) by fitting the model to permeability data.
- Utilized dimensionless groups (R and sigma) to analyze experimental data and determine permeation pathways.
Main Results:
- The stratum corneum (SC) permeation is predominantly via the transcellular pathway for most compounds, independent of lipophilicity.
- The developed model shows improved overall fit compared to the Potts-Guy equation, especially in estimating lag times.
- Simple approximations allow for spreadsheet implementation of the full numerical solution.
Conclusions:
- The refined SC microtransport model provides a more accurate representation of skin permeation dynamics.
- The dominance of the transcellular pathway offers a new perspective on SC barrier function.
- The model's enhanced predictive capabilities for lag times and transient profiles are valuable for formulation development.
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