Skip to main content
Log in

Electrochemical Characterization of Human Skin by Impedance Spectroscopy: The Effect of Penetration Enhancers

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model with modern fractal mathematics, the effect of enhancers on the surface of skin is demonstrated. The enhancers appeared to open new penetration routes and increase the ohmic resistance, capacitive properties, and fractal dimension of skin, which means a rougher or more heterogeneous surface.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. 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 

  2. T. Yamamoto and Y. Yamamoto. Electrical properties of the epidermal stratum corneum. Med. Biol. Eng. 14:151–158 (176).

    Google Scholar 

  3. T. Yamamoto and Y. Yamamoto. Analysis for the change of skin impedance. Med. Biol. Eng. Comput. 15:219–227 (1977).

    Google Scholar 

  4. T. Yamamoto and Y. Yamamoto. Dispersion and correlation of the parameters for skin impedance. Med. Biol. Eng. Comput. 16:592–594 (1978).

    Google Scholar 

  5. Y. Yamamoto, T. Yamamoto, S. Ohta, T. Uehara, S. Tahara, and Y. Ishizuka. The measurement principle for evaluating the performance of drugs and cosmetics by skin impedance. Med. Biol. Eng. Comput. 16:623–632 (1978).

    Google Scholar 

  6. S. Grimnes. Skin impedance and electro-osmosis in the human epidermis. Med. Biol. Eng. Comput. 21:739–749 (1983).

    Google Scholar 

  7. A. Boxtel. Skin resistance during square-wave electrical pulses of 1 to 10 mA. Med. Biol. Eng. Comput. 15:679–687 (1977).

    Google Scholar 

  8. J. Rosell, J. Colominas, P. Riu, R. Pallas-Areny, and J. G. Webster. Skin impedance from 1 Hz to 1 MHz. IEEE Trans. Biomed. Eng. 35:649–651 (1988).

    Google Scholar 

  9. J. D. DeNuzzio and B. Berner. Electrochemical and iontophoretic studies of human skin. J. Contr. Release 11:105–112 (1990).

    Google Scholar 

  10. R. R. Burnette and B. Ongpipattanakul. Characterization of the permselective properties of excised human skin during iontophoresis. J. Pharm. Sci. 76:765–773 (1987).

    Google Scholar 

  11. R. R. Burnette and B. Ongpipattanakul. Characterization of the pore transport properties and tissue alteration of excised human skin during iontophoresis. J. Pharm. Sci. 77:132–137 (1988).

    Google Scholar 

  12. M. J. Pikal. Transport mechanisms in iontophoresis. I. A theoretical model for the effect of electroosmotic flow on flux enhancement in transdermal iontophoresis. Pharm. Res. 7:118–126 (1990).

    Google Scholar 

  13. M. J. Pikal and S. Shah. Transport mechanisms in iontophoresis. II. Electroosmotic flow and transference number measurements for hairless mouse skin. Pharm. Res. 7:213–221 (1990).

    Google Scholar 

  14. 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 

  15. S. M. Sims. Iontophoretic Transport Mechanisms Across Skin, Dissertation thesis, University of Utah, Salt Lake City, 1991.

    Google Scholar 

  16. 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 

  17. A. K. Banga and Y. W. Chien. Iontophoretic delivery of drugs: Fundamentals, developments and biomedical applications. J. Contr. Release 7:1–24 (1988).

    Google Scholar 

  18. J. Hirvonen, J. H. Rytting, P. Paronen, and A. Urtti. Dodecyl N,N-dimethylamino acetate and Azone enhance drug penetration across human, snake, and rabbit skin. Pharm. Res. 8:933–937 (1991).

    Google Scholar 

  19. B. A. Boukamp. A nonlinear least square fit procedure for analysis of immittance data of electrochemical systems. Solid State Ion. 20:31–44 (1986).

    Google Scholar 

  20. K. S. Cole. Membranes, Ions and Impulses, University of California Press, Berkeley, 1968.

    Google Scholar 

  21. J. R. MacDonald (ed.). Impedance Spectroscopy, John Wiley, New York, 1987.

    Google Scholar 

  22. T. Pajkossy. Electrochemistry at fractal surfaces. J. Electroanal. Chem. 300:1–11 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. R. F. Voss. In H. O. Peitgen and D. Saupe (eds.), The Science of Fractal Images, Springer-Verlag, New York, 1988, Chap. 4.

    Google Scholar 

  24. P. M. Elias. Epidermal barrier function: Intercellular lamellar lipid structures, origin, composition and metabolism. J. Contr. Release 15:199–208 (1991).

    Google Scholar 

  25. J. Hirvonen, R. Rajala, E. Laine, P. Paronen, and A. Urtti. Penetration enhancers dodecyl N,N-dimethylamino acetate and Azone alter the structure of the skin—A DSC study. In R. C. Scott, H. E. Bodde, R. H. Guy, and J. Hadgraft (eds.), Proceedings of the 2nd Conference of Prediction of Percutaneous Penetration, Southampton 2:350–354 (1991).

  26. B. Dubuc, S. W. Zucker, C. Tricot, J. F. Quiniou, and D. Wehbi. Evaluating the fractal dimension of surfaces. Proc. R. Soc. London A425:113–127 (1989).

    Google Scholar 

  27. C. Moler, J. Little, and S. Bangert. PC-MATLAB for MS-DOS Personal Computers, The MathWorks Inc., 1987.

  28. J. Hirvonen, K. Kontturi, L. Murtomäki, P. Paronen, and A. Urtti. Transdermal iontophoresis of sotalol and salicylate; the effect of skin charge and penetration enhancers. J. Contr. Release (submitted).

  29. J.-P. Diard, B. Le Gorrec, and C. Montella. Calculation, simulation and interpretation of electrochemical impedances. J. Electroanal. Chem. 326:13–36 (1992).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kontturi, K., Murtomäki, L., Hirvonen, J. et al. Electrochemical Characterization of Human Skin by Impedance Spectroscopy: The Effect of Penetration Enhancers. Pharm Res 10, 381–385 (1993). https://doi.org/10.1023/A:1018984121415

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018984121415

Navigation