Erick A. White

On the correlation between single-frequency impedance measurements and human skin permeability to water

The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000 Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated. Compared with urea and mannitol, which are known to permeate skin through a polar pathway, the value of kp for water was found to be about two times larger than expected for transport through only the polar pathway, suggesting an approximately equal contribution from the lipophilic pathway. Equations relating kp to (RPARA) and (RskinA) were used to compare on a consistent basis proposed tests for identifying and excluding damaged skin from chemical absorption studies. The criterion of 20 kΩ cm2 for (RskinA) corresponds to a tritiated water permeability of 3.2×10(-3) cm/h, which should exclude damaged skin without screening undamaged but higher permeability skin samples from study.

Characterization of Damaged Skin by Impedance Spectroscopy: Mechanical Damage

PurposeElectrochemical impedance spectroscopy is a convenient method that has been used to characterize skin barrier function, which affects drug delivery into and through the skin. The objective of this study was to relate changes in skin barrier function arising from mechanical damage to changes in the impedance spectra. These observations are compared in a companion paper to changes in chemically damaged skin.MethodsElectrical impedance and the permeation of a non-polar compound were measured before and after human cadaver skin was damaged by needle puncture.ResultsThe impedance responses of all skin samples were consistent with an equivalent circuit model with a resistor and constant phase element (CPE) in parallel. Pinhole-damaged skin exhibited a lower resistance pathway acting in parallel with the skin resistance without changing the CPE behavior. The characteristic frequency of the impedance scans determined after needle puncture increased by an amount that could be predicted. The flux of 4-cyanophenol increased by a small but significant amount that did not correlate with the hole resistance calculated under the assumption that the resistance of the surrounding skin did not change.ConclusionsSkin impedance measurements are sensitive to irreversible damage caused by exposure to puncture with a needle.

A critical analysis of single-frequency LCR databridge impedance measurements of human skin

Testing whether the barrier of skin samples has sufficient integrity for meaningful measurements of in-vitro chemical permeability is usually required when data are generated for regulatory purposes. Recently, skin integrity has been assessed using LCR databridge measurements, which are reported as resistances determined in either series (SER) or parallel (PAR) modes at a single frequency, typically 100 or 1000Hz. Measurements made at different combinations of mode and frequency are known to differ, although the skin literature reveals confusion over the meaning of these differences and the impact on the interpretation of integrity test results. Here, the theoretical meanings of resistance and capacitance measurements in PAR and SER mode are described and confirmed experimentally. SER-mode resistances are equal to the real part of the complex impedance; whereas, PAR-mode resistances are the inverse of the real part of the admittance. Capacitance measurements reported in SER and PAR modes are similar manipulations of the imaginary parts of the complex impedance and admittance. A large body of data from human cadaver skin is used to show that the PAR-mode resistance and SER-mode capacitance measured at 100Hz are sensitive to skin resistivity, which is the electrical measurement most closely related to skin integrity.

On the Use of the power-law model for interpreting constant-phase-element parameters

Constant-phase elements (CPE) are often used to fit impedance data arising from a broad range of experimental systems. The power-law model has proven to be a powerful tool for interpretation of CPE parameters resulting from an axial or normal distribution of time constants. This paper addresses difficulties in applying this model associated with uncertain values for one of the model parameters. Methods are presented for bounding the value of the parameter, for calibration, and for comparative analysis in which the unknown parameter may be eliminated. The methods are illustrated by data taken from the literature for oxides on steels and for human skin.