In Vivo ac Impedance Spectroscopy of Human Skin: Theory and Problems in Monitoring of Passive Percutaneous Drug Delivery

: The use of impedance spectroscopy to evaluate transdermal drug delivery is discussed and new techniques and protocols are suggested to avoid or minimize potential problems. A novel multichannel impedance analyzer, exploiting the advantages of the “three‐electrode” configuration, was employed to measure the effects of differing topically applied concentrations of the percutaneous local anesthetic amethocaine on the electrical properties of the treated skin sites. Each measured impedance spectrum was modeled by an equivalent circuit consisting of a resistor in series with the parallel combination of a pseudocapacitance and a resistor. Due to differences in skin sites and to the finite times taken to apply each electrode, it was difficult to satisfactorily compare and contrast the results obtained from adjacent skin sites. Normalization of data highlighted differences in relative impedance changes and aided the meaningful comparison of treated skin sites.