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

Abstract

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.

In vivo electrical characteristics of human skin, including at biological active points

“…As can be seen from Fig. 3, a major portion of the impedance spectrum of human skin lies in the frequency range of 3-100 Hz; this is in good agreement with an earlier paper (LANCKERMEIER et al, 1999). The major portion of the impedance arc for human skin is in the frequency range o f 10-100 Hz.…”

“…The described equivalent scheme is different from those proposed before (LANCKERMEIER et al, 1999;KALIA et al, 1996;KONTTURI et al, 1993;KONTURRI and MURTOMAKI, 1994;DORGAN and REILLY, 1999;SASSER et al, 1993) by an additional R-C circuit, in the case of the skin, the parameters R R and C R of the body are such that the low-frequency depressed semicircle dominates. In the BAP reading, the additional resistance Rp and capacitance Cp are due to the appearance, in the impedance spectrum of the BAPs, of the two low-and high-frequency semicircular arcs.…”

“…There are many electrical models of skin described in the literature, from a simple RC circuit to more complicated circuits with constant phase elements (LANCKERMEIER et al, 1999;KALIA et al, 1996;KONTTURI et al, MURTOMAKI, 1994;DORGAN and REILLY, 1999;SASSER et al, 1993). In all these models, the data are described using only one semicircle, whereas we clearly have two semicircles.…”

“…ELECTRICAL MEASUREMENTS of human skin, with the help of different impedance methods, are non-invasive and widely used for various clinical applications, such as bio-electrical impedance analysis, electrical impedance tomography, investigation of transdermal drug delivery and others (HANNAN et a l., 1995;BARBER et al, 1983;LANCKERMEIER et al, 1999;GRIFFITHS, 1995).…”

The Contributions of the Celtic Masters and Their Associates

“…The rapid onset and prolonged duration of topical anaesthesia from these systems was supported by extensive evidence of comparative permeability rates across a wide formulation space. Novel methods, including the use of alternating-current impedance spectroscopy [41,42] were used to determine in vitro and in vivo performance. For example, in this case, the onset time and duration of anaesthesia could be determined by non-invasive in vivo experiments and related directly to findings from laboratory studies.…”