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In Silico Prediction of Percutaneous Absorption and Disposition Kinetics of Chemicals

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Abstract

Purpose

To develop in-silico model for predicting percutaneous absorption and disposition kinetics of chemicals in skin layers so as to facilitate the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure.

Methods

A general-purpose computer model for simulating skin permeation, absorption and disposition kinetics in the stratum corneum, viable dermis and dermis has been developed. Equations have been proposed for determining the partition and diffusion properties of chemicals by considering molecular partition, binding and mobility in skin layers. In vitro skin penetration data of 12 chemicals was used to validate the model.

Results

The observed and simulated permeation and disposition in skin layers were compared for 12 tested chemicals. For most tested chemicals, the experimental and model results are in good agreement with the coefficient of determination >0.80 and relative root mean squared error <1.20. The disposition kinetic parameters of the maximum concentration and the area under the curve in the viable epidermis and dermis initially increased with hydrophobicity, but reached maxima and then decreased with further increase of hydrophobicity.

Conclusions

By considering skin physiological structure and composition, the partition and diffusion properties of chemicals in skin layers are determined. This allows in-silico simulation of percutaneous permeation, absorption and disposition kinetics of wide chemical space. The model produced results in good agreement with experimental data of 12 chemicals, suggesting a much improved framework to support transdermal delivery of drug and cosmetic actives as well as integrated risk assessment.

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ACKNOWLEDGMENTS AND DISCLOSURES

This research is supported by Unilever R&D Colworth UK, Program for New Century Excellent Talents in University (Project No. NCET-11-0477), and Program for Changjiang Scholars and Innovative Research Team in University (Project No. IRT1293). We wish to thank Cameron MacKay and Michael Davies for providing skin absorption data and helpful comments on the manuscript.

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Authors and Affiliations

  1. College of Engineering, China Agricultural University (East Campus), P.O. Box 191, 17 Qing-Hua-Dong-Lu, Beijing, 100083, People’s Republic of China

    Longjian Chen & Lujia Han

  2. Unilever Research Colworth, Colworth Park, Sharnbrook, Bedfordshire, MK44 1LQ, UK

    Ouarda Saib & Guoping Lian

  3. Department of Chemical and Process Engineering, University of Surrey, Guildford, GU2 7XH, UK

    Guoping Lian

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  1. Longjian Chen
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  2. Lujia Han
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  3. Ouarda Saib
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  4. Guoping Lian
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Correspondence to Lujia Han or Guoping Lian.

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Chen, L., Han, L., Saib, O. et al. In Silico Prediction of Percutaneous Absorption and Disposition Kinetics of Chemicals. Pharm Res 32, 1779–1793 (2015). https://doi.org/10.1007/s11095-014-1575-0

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  • DOI: https://doi.org/10.1007/s11095-014-1575-0

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