Current profile regulates iontophoretic delivery of amino acids across the skin

J. Hirvonen, F. Hueber, R. H. Guy

Research output: Contribution to journalArticlepeer-review


In most of the reported studies of iontophoresis, direct current (DC), continuously applied for a defined period, has been used. However, this current profile can result in skin polarization and irritation. Therefore, the impact of alternative current profiles in regulating the permeation of two charged amino acids, lysine and glutamic acid, has been studied. The current profiles considered were: (1) none (passive control); (2) DC; (3) square-wave alternating current (AC) with different bipolar duty cycles (i.e., +/- ratios); (4) sine-wave AC; and (5) pulsed DC with different on/off ratios. Drug flux (nmol/cm2 per h), cumulative drug permeation (%), and amount of the drug in the skin after iontophoresis were determined in vitro using hairless mouse skin. The principal findings were: (1) Iontophoretic transport can be significantly modified and regulated by the use of different current profiles. (2) In terms of total transmembrane drug delivery, constant DC is most efficient; pulsed DC, even at comparable charge, may not deliver as much drug as uninterrupted DC. (3) Square-wave and sine-wave AC profiles (again, at comparable total charge) result in comparable transport rates. (4) Lysine and glutamic acid fluxes are directly proportional to the unipolar square-wave (positive) duty cycle; with bipolar AC (positive and negative), measurable drug delivery requires a threshold of 50% positive duty cycle, whereafter amino acid delivery is linear to 100%. (5) The frequency (2.5-2500 Hz) does not significantly effect the delivery of these small molecules. Pulsed iontophoresis, bipolar or unipolar, may be used as an effective and, potentially, better tolerated means of transdermal drug delivery relative to constant DC. The iontophoretic delivery of charged species can be controlled over a wide range, therefore, by appropriate regulation of the current profile and/or duty cycle.

Original languageEnglish
Pages (from-to)239-249
Number of pages11
JournalJournal of Controlled Release
Issue number3
Publication statusPublished - 31 Dec 1995


  • Current profile
  • Glutamic acid
  • Iontophoresis
  • Lysine
  • Transdermal drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science


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