Skip to main content
SpringerLink
Log in

Hindered Diffusion of Polar Molecules Through and Effective Pore Radii Estimates of Intact and Ethanol Treated Human Epidermal Membrane

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

The in vitro passive transport of urea, mannitol, sucrose and raffinose across intact and ethanol treated human epidermal membrane was investigated. The intent of this study was to characterize the barrier properties and permeation pathways of these membranes for polar permeants under passive conditions. Based upon the relative permeabilities of these four solutes and hindered diffusion theory, the experimental data was adequately modeled for both membrane systems according to permeation through a porous membrane. Effective pore radii estimates for intact human epidermal membrane fell between 15 Å to 25 Å while similar estimates fell compactly between 15 Å to 20 Å for ethanol treated human epidermal membrane. Similarities between the relative permeabilities of human epidermal membrane for the four permeants studied and the relative permeabilities of these same permeants through ethanol pretreated human epidermal membrane indicate that significant similarities exist between the permeation pathways for both membrane systems. The results of this study have important implications for transdermal drug delivery in general and more specifically for strategies of designing effective chemical permeation enhancement systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. R. J. Scheuplein and I. H. Blank. Permeability of skin. Physiol. Rev. 51:702–747 (1971).

    Google Scholar 

  2. A. S. Michaels, S. K. Chandrasekaran, and J. E. Shaw. Drug permeation through human skin: Theory and in vitro experimental measurement. AIChE J. 21:985–996 (1975).

    Google Scholar 

  3. P. V. Raykar, M. C. Fung, and B. D. Anderson. The role of protein and lipid domains in the uptake of solutes by human stratum corneum. Pharm. Res. 5:140–150 (1988).

    Google Scholar 

  4. T. Hatanaka, M. Shimoyama, K. Sugibayashi, and Y. Morimoto. Effect of vehicle on the skin permeability of drugs: Polyethylene glycol 400-water and ethanol-water binary solvents. J. Controlled Release 23:247–260 (1993).

    Google Scholar 

  5. C. Ackermann, G. L. Flynn, and W. M. Smith. Ether-water partitioning and permeability through nude mouse skin in vitro. II. Hydrocortisone 21-n-alkyl esters, alkanols and hydrophilic compounds. Int. J. Pharm. 36:67–71 (1987).

    Google Scholar 

  6. Y. H. Kim, A. H. Ghanem, H. Mahmoud, and W. I. Higuchi. Short chain alkanols as transport enhancers for lipophilic and polar/ionic permeants in hairless mouse skin: Mechanism(s) of action. Int. J. Pharm. 80:17–31 (1992).

    Google Scholar 

  7. R. O. Potts and R. H. Guy. Predicting skin permeability. Pharm. Res. 9:663–669 (1992).

    Google Scholar 

  8. V. Srinivasan, W. I. Higuchi, S. M. Sims, A. H. Ghanem, and C. R. Behl. Transdermal iontophoretic drug delivery. Mechanistic analysis and application to polypeptide delivery. J. Pharm. Sci. 78:370–375 (1989).

    Google Scholar 

  9. T. Kurihara-Bergstrom, K. Knutson, L. J. DeNoble, and C. Y. Goates. Percutaneous absorption enhancement of an ionic molecule by ethanol-water systems in human skin. Pharm. Res. 7:762–766 (1990).

    Google Scholar 

  10. P. A. Cornwell and B. W. Barry. The routes of penetration of ions and 5-fluorouracil across human skin and the mechanisms of action of terpene skin penetration enhancers. Int. J. Pharm. 94:189–194 (1993).

    Google Scholar 

  11. T. M. Tuvunen, S. Buyuktimkin, N. Buyuktimkin, A. Urtti, P. Paronen, and J. H. Rytting. Enhanced delivery of 5-fluorouracil through shed snake skin by two new transdermal penetration enhancers. Int. J. Pharm. 92:89–95 (1993).

    Google Scholar 

  12. S. B. Ruddy and B. W. Hadzija. Iontophoretic permeability of polyethylene glycols through hairless rat skin: Application of hydrodynamic theory for hindered transport through liquid-filled pores. Drug Design and Discovery 8:207–224 (1992).

    Google Scholar 

  13. S. M. Sims, W. I. Higuchi, and V. Srinivasan. Skin alteration and convective solvent flow effects during iontophoresis: I. Neutral solute transport across human skin. Int. J. Pharm. 69:109–121 (1991).

    Google Scholar 

  14. J. C. Keister and G. B. Kasting. A kinetic model for ion transport across skin. J. Membrane Sci. 71:257–271 (1992).

    Google Scholar 

  15. H. Inada, A. H. Ghanem, and W. I. Higuchi. Studies on the effects of applied voltage and duration on human epidermal membrane alteration/recovery and the resultant effects upon iontophoresis. Pharm. Res. 11:687–697 (1994).

    Google Scholar 

  16. M. J. Pikal and S. Shah. Transport mechanisms in iontophoresis. III. An experimental study of the contributions of electroosmotic flow and permeability change in transport of low and high molecular weight solutes. Pharm. Res. 7:222–229 (1990).

    Google Scholar 

  17. W. M. Deen. Hindered transport of large molecules in liquid-filled pores. AIChE J. 33:1409–1425 (1987).

    Google Scholar 

  18. R. E. Beck and J. S. Schultz. Hindrance of solute diffusion within membranes as measured with microporous membranes of known pore geometry. Biochim. Biophys. Acta 255:272–303 (1972).

    Google Scholar 

  19. R. A. Conradi, A. R. Hilgers, N. F. H. Ho, and P. S. Burton. The influence of peptide structure on transport across caco-2 cells. Pharm. Res. 8:1453–1459 (1991).

    Google Scholar 

  20. T. Inamori, A. H. Ghanem, W. I. Higuchi, and V. Srinivasan. Macromolecular transport in and effective pore size of ethanol pretreated human epidermal membrane. Int. J. Pharm. 105:113–123 (1994).

    Google Scholar 

  21. W. M. Deen, M. P. Bohrer, and N. B. Epstein. Effect of molecular size and configuration on diffusion in microporous membranes. AIChE J. 27:952–959 (1981).

    Google Scholar 

  22. K. D. Peck, A. H. Ghanem, W. I. Higuchi, and V. Srinivasan. Improved stability of the human epidermal membrane during successive permeability experiments. Int. J. Pharm. 98:141–147 (1993).

    Google Scholar 

  23. P. Liu, J. A. S. Nightingale, and T. Kurihara-Bergstrom. Variation of human skin permeation in vitro: Ionic vs neutral compounds. Int. J. Pharm. 90:171–176 (1993).

    Google Scholar 

  24. S. M. Sims, W. I. Higuchi, V. Srinivasan, and K. Peck. Ionic partition coefficients and electroosmotic flow in cylindrical pores: Comparison of the predictions of the Poisson-Boltzmann equation with experiment. J. Colloid Interface Sci. 155:210–220 (1993).

    Google Scholar 

  25. V. A. Gierer and K. Wirtz. Molekulare theorie der mikroreibung. Z. Naturforsch. 8a:532–538 (1953).

    Google Scholar 

  26. A. Leo, C. Hansch and D. Elkins. Partition coefficients and their uses. Chem. Rev. 71:525–616 (1971).

    Google Scholar 

  27. W. D. Stein. Transport and Diffusion Across Cell Membranes, Academic Press, Orlando, 1986.

    Google Scholar 

  28. G. M. Golden, D. B. Guzek, A. H. Kennedy, J. E. Mckie, and R. O. Potts. Stratum corneum lipid phase transitions and water barrier properties. Biochem. 26:2382–2388 (1986).

    Google Scholar 

  29. E. R. Scott, A. I. Laplaza, H. S. White, and J. B. Phipps. Transport of ionic species in skin: Contribution of pores to the overall skin conductance. Pharm. Res. 10:1699–1709 (1993).

    Google Scholar 

  30. G. B. Kasting and L. A. Bowman. Electrical analysis of fresh, excised human skin: A comparison with frozen skin. Pharm. Res. 7:1141–1146 (1990).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112

    Kendall D. Peck, Abdel-Halim Ghanem & William I. Higuchi

Authors
  1. Kendall D. Peck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdel-Halim Ghanem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William I. Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peck, K.D., Ghanem, AH. & Higuchi, W.I. Hindered Diffusion of Polar Molecules Through and Effective Pore Radii Estimates of Intact and Ethanol Treated Human Epidermal Membrane. Pharm Res 11, 1306–1314 (1994). https://doi.org/10.1023/A:1018998529283

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018998529283

Search

Navigation