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Non Steady-state Descriptions of Drug Permeation Through Stratum Corneum. I. The Biphasic Brick-and-Mortar Model

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Abstract

Purpose. The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases.

Methods. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated.

Results. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and corneocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases.

Conclusions. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.

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REFERENCES

  1. F. de Haan, H. Boddé, W. de Bruijn, L. Ginsel, and H. Junginger. Visualising drug transport across stratum corneum: cryotechniques, vapour fixation, autoradiography. Int. J. Pharm. 56:75–86, 1989.

    Google Scholar 

  2. M. Lampe, A. Burlinghame, J. Whitney, M. Williams, B. Brown, E. Roitman, and P. Elias. Humans stratum corneum lipids: characterisation and regional variation. J. Lipid Res, 24:120–130, 1983.

    Google Scholar 

  3. P. Elias. Epidermal barrier function: intercellular lamellar lipid structures, origin, composition and metabolism. J. Cont. Rel, 15:199–208, 1991.

    Google Scholar 

  4. J. Bouwstra, M. de Vries, G. Gooris, W. Bras, J. Brussee, and M. Ponec. Thermodynamic and structural aspects of the skin barrier. J. Cont. Rel, 15:227–236, 1991.

    Google Scholar 

  5. B. Forslind. A domain mosaic model of the skin barrier. Acta Derm. Venerol, 74:1–6, 1993.

    Google Scholar 

  6. T. Degim, J. Hadgraft, and W. Pugh, Prod. Int. Sym. Cont. Rel. Bio. Mater., 22:652, 1995.

    Google Scholar 

  7. C. Maxwell. Treatise on Electricity and Magnetism. Oxford University Press, London. I:365, 1873.

    Google Scholar 

  8. W. Albery and J. Hadgraft. Percutaneous absorption: in vivo experiments. J. Pharm. Pharmacol. 31:140–147, 1978.

    Google Scholar 

  9. R. Lange-Lieckfeld and G. Lee. Use of a model lipid matrix to demonstrate the dependence of the stratum corneum's barrier properties on its internal geometry. J. Cont. Rel. 20:183–194, 1992.

    Google Scholar 

  10. A. Michaels, S. Chandrasekaran, and J. Shaw. Drug permeation through human skin: theory and in vitro experimental measurement. AIChE J. 21:985–996, 1975.

    Google Scholar 

  11. K. Tojo. Brick model for drug transport across stratum corneum, J. Pharm. Sci. 76:889–891, 1987.

    Google Scholar 

  12. D. Edwards and R. Langer. A linear theory of transdermal transport phenomena. J. Pharm. Sci, 83:1315–1334, 1994.

    Google Scholar 

  13. R. Lieckfeld, J. Villalaín, J. Gómes-Fernándes, and G. Lee. Diffusivity and structural polymorphism in some model stratum corneum lipid systems. Biochim. Biophys. Acta. 1151:182–188, 1993.

    Google Scholar 

  14. W. Hackbusch. On first and second order base schemes. Computing 41:277–296, 1989.

    Google Scholar 

  15. W. Hackbusch. Multi-grid Methods and Applications. Springer, Berlin, 1985.

    Google Scholar 

  16. G. Wittum. On the robustness of ILU-smoothing. SIAM, J. Sci. Stat. Comp. 10:699–717, 1989.

    Google Scholar 

  17. P. Bastian and G. Wittum. Adaptivity and robustness. In: Adaptive Methods-Algorithms, Theory and Applications. Hackbusch, W., and Wittum, G. eds. NNFM, Braunschweig, 1994.

    Google Scholar 

  18. J. Crank. The Mathematics of Diffusion. Oxford University Press, London, 49–53, 1975.

    Google Scholar 

  19. H. Boddé, I. van den Brink, H. Koerten, and F. de Haan. Visualisation of in vitro percutaneous penetration of mercuric chloride; transport through intercellular space versus cellular uptake through desmosomes. J. Cont. Rel. 15:227–236, 1991.

    Google Scholar 

  20. B. Barry. Dermatological Formulations, Marcel Dekker, New York, 1983.

    Google Scholar 

  21. M. Fartasch and M. Ponec. Improved barrier structure formation in air-exposed human keratinocyte culture systems. J. Invest. Dermatol. 102:366–374, 1994.

    Google Scholar 

  22. S. Teng. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell 30:361–363, 1982.

    Google Scholar 

  23. D. Swartzendruber, P. Werz, K. Madison, and D. Downing. Evidence that the corneocyte has a chemically bound lipid envelope. J. Invest. Dermatol. 88:709–713, 1987.

    Google Scholar 

  24. K. Packer and T. Sellwood. Proton magnetic resonance studies of hydrated stratum corneum. J. Chem. Soc. Faraday II. 74:1592–1605, 1978.

    Google Scholar 

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Heisig, M., Lieckfeldt, R., Wittum, G. et al. Non Steady-state Descriptions of Drug Permeation Through Stratum Corneum. I. The Biphasic Brick-and-Mortar Model. Pharm Res 13, 421–426 (1996). https://doi.org/10.1023/A:1016048710880

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  • DOI: https://doi.org/10.1023/A:1016048710880

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