title: Alternating current (AC) iontophoretic transport across human epidermal membrane: effects of AC frequency and amplitude.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors: Guang
authors: G
authors: Yan
authors: Qingfang
authors: Q
authors: Xu
authors: Yuri G
authors: YG
authors: Anissimov
authors: Jinsong
authors: J
authors: Hao
authors: William I
authors: WI
authors: Higuchi
authors: S Kevin
authors: SK
authors: Li
mesh_terms: D000279:Administration, Cutaneous; D001089:Arabinose / Q000008:administration & dosage / Q000378:metabolism*; D004058:Diffusion; D017097:Electric Impedance; D053841:Electroosmosis; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D008954:Models, Biological; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D019789:Tetraethylammonium / Q000008:administration & dosage / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D019789:Tetraethylammonium; D001089:Arabinose
references: J Pharm Sci. 2001 Jul;90(7):932-42
references: 11458340
references: Med Biol Eng Comput. 2005 Sep;43(5):622-9
references: 16411635
references: Diabetes Metab Res Rev. 2002 Jan-Feb;18 Suppl 1:S49-53
references: 11921430
references: J Control Release. 2002 Aug 21;82(2-3):249-61
references: 12175741
references: J Invest Dermatol. 2003 Feb;120(2):275-84
references: 12542533
references: J Control Release. 2003 Apr 14;89(1):31-46
references: 12695061
references: J Med Dent Sci. 2003 Mar;50(1):71-7
references: 12715922
references: J Control Release. 2003 Sep 4;91(3):327-43
references: 12932711
references: Pharm Res. 1994 May;11(5):687-97
references: 8058638
references: Pharm Res. 1994 Sep;11(9):1306-14
references: 7816761
references: Arch Phys Med Rehabil. 1995 May;76(5):463-6
references: 7741619
references: Nat Med. 1995 Nov;1(11):1198-201
references: 7584995
references: J Invest Dermatol. 1996 Jan;106(1):89-95
references: 8592088
references: J Pharm Sci. 1997 Oct;86(10):1162-72
references: 9344175
references: Biophys J. 1998 Feb;74(2 Pt 1):843-56
references: 9533696
references: J Pharm Sci. 1999 Apr;88(4):419-27
references: 10187752
references: J Pharm Sci. 1999 Oct;88(10):1044-9
references: 10514354
references: J Pharm Sci. 2004 Dec;93(12):2895-908
references: 15459891
references: J Pharm Sci. 2005 Mar;94(3):547-58
references: 15637683
references: J Pharm Sci. 2005 Aug;94(8):1839-49
references: 15986462
references: J Control Release. 2005 Dec 10;110(1):141-50
references: 16289410
references: Int J Pharm. 2002 Jan 31;232(1-2):45-57
references: 11790489