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Alternating Current (AC) Iontophoretic Transport across Human Epidermal Membrane: Effects of AC Frequency and Amplitude

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Abstract

Purpose

As a continuing effort to understand the mechanisms of alternating current (AC) transdermal iontophoresis and the iontophoretic transport pathways in the stratum corneum (SC), the objectives of the present study were to determine the interplay of AC frequency, AC voltage, and iontophoretic transport of ionic and neutral permeants across human epidermal membrane (HEM) and use AC as a means to characterize the transport pathways.

Materials and Methods

Constant AC voltage iontophoresis experiments were conducted with HEM in 0.10 M tetraethyl ammonium pivalate (TEAP). AC frequencies ranging from 0.0001 to 25 Hz and AC applied voltages of 0.5 and 2.5 V were investigated. Tetraethyl ammonium (TEA) and arabinose (ARA) were the ionic and neutral model permeants, respectively. In data analysis, the logarithm of the permeability coefficients of HEM for the model permeants was plotted against the logarithm of the HEM electrical resistance for each AC condition.

Results

As expected, linear correlations between the logarithms of permeability coefficients and the logarithms of resistances of HEM were observed, and the permeability data were first normalized and then compared at the same HEM electrical resistance using these correlations. Transport enhancement of the ionic permeant was significantly larger than that of the neutral permeant during AC iontophoresis. The fluxes of the ionic permeant during AC iontophoresis of 2.5 V in the frequency range from 5 to 1,000 Hz were relatively constant and were approximately 4 times over those of passive transport. When the AC frequency decreased from 5 to 0.001 Hz at 2.5 V, flux enhancement increased to around 50 times over passive transport.

Conclusion

While the AC frequency for achieving the full effect of iontophoretic enhancement at low AC frequency was lower than anticipated, the frequency for approaching passive diffusion transport at high frequency was higher than expected from the HEM morphology. These observations are consistent with a transport model of multiple barriers in series and the previous hypothesis that the iontophoresis pathways across HEM under AC behave like a series of reservoirs interconnected by short pore pathways.

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Acknowledgments

This research was supported by NIH Grant GM 063559. The authors thank Watson Pharmaceuticals Inc. (Salt Lake City, UT) for their generous donation of some of the HEM samples used in the present study and Dr. Michael S. Roberts for his helpful discussion.

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Authors and Affiliations

  1. Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112, USA

    Guang Yan, William I. Higuchi & S. Kevin Li

  2. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, Rm 136 HPB, Cincinnati, Ohio, 45267, USA

    Qingfang Xu, Jinsong Hao & S. Kevin Li

  3. School of Biomolecular and Physical Sciences, Griffith University, Nathan, Queensland, 4111, Australia

    Yuri G. Anissimov

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  1. Guang Yan
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  2. Qingfang Xu
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  3. Yuri G. Anissimov
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  5. William I. Higuchi
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  6. S. Kevin Li
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Correspondence to S. Kevin Li.

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Yan, G., Xu, Q., Anissimov, Y.G. et al. Alternating Current (AC) Iontophoretic Transport across Human Epidermal Membrane: Effects of AC Frequency and Amplitude. Pharm Res 25, 616–624 (2008). https://doi.org/10.1007/s11095-007-9405-2

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  • DOI: https://doi.org/10.1007/s11095-007-9405-2

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