Effects of alternating current frequency and permeation enhancers upon human epidermal membrane

• Published in: International journal of pharmaceutics 2009-05, Vol.372 (1), p.24-32
• Main Authors: Xu, Qingfang, Kochambilli, Rajan P., Song, Yang, Hao, Jinsong, Higuchi, William I., Li, S. Kevin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Constant skin resistance AC iontophoresis; Electric Conductivity; Electric Impedance; Epidermis - drug effects; Epidermis - metabolism; Female; General pharmacology; Human epidermal membrane; Humans; In Vitro Techniques; Iontophoresis - instrumentation; Iontophoresis - methods; Male; Medical sciences; Middle Aged; Permeability - drug effects; Permeation enhancer; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pyrrolidinones - administration & dosage; Pyrrolidinones - pharmacokinetics; Skin Absorption - drug effects; Skin Absorption - physiology; Skin electrical resistance; Young Adult
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2008.12.036

Previous studies have demonstrated the ability of AC iontophoresis to control skin resistance in different transdermal iontophoresis applications. The objectives of the present study were to (a) identify the alternating current (AC) frequency for the optimization of AC pore induction of human epidermal membrane (HEM) and (b) determine the effects of chemical permeation enhancers upon the extent of pore induction under AC conditions. Experiments with a synthetic membrane system were first conducted as the control. In these synthetic membrane experiments, the electrical resistance of the membrane remained essentially constant, suggesting constant electromobility of the background electrolyte ions under the AC conditions studied. In the HEM experiments, the electrical resistance data showed that higher applied voltages were required to induce the same extent of pore induction in HEM at AC frequency of 1 kHz compared with those at 30 Hz. Even higher voltages were needed at AC frequencies of 10 kHz and higher. AC frequency also influenced the recovery of HEM electrical resistance after AC iontophoresis application. An optimal AC frequency region for effective pore induction and least sensation was proposed. Permeation enhancers were shown to enhance pore induction in HEM during AC iontophoresis. The enhancers reversibly reduced the AC voltage required to sustain a constant state of pore induction in HEM during AC iontophoresis, consistent with the mechanism of lipid lamellae electroporation in the stratum corneum.