Skin impedance

IN VITRO SKIN IMPEDANCE GUIDED HIGH-THROUGHPUT SCREENING... 

Figure 4 (A) Schematic of in vitro skin impedance guided high-throughput screening tool, INSIGHT. (B) Skin permeability skin impedance correlation for 1.5%wt/vol. menthol (open squares), 1.5%wt/vol. lauric acid (filled triangles), 1.5%wt/vol. Brij 35 (open circles), 1.0%wt/vol. Lauryl sarcosinate (filled circles), 1.0%wt/vol. sorbitan monolaurate (open triangles), and 1.5%wt/vol. benzyldodecyldimethyl ammonium chloride (filled squares) in 1 1 PBS EtOH. Abbreviation PBS EtOH, phosphate buffered saline ethanol.

INSIGHT uses the fundamental correlation between the electrical and permeability properties of skin. Skin permeability shows a strong correlation with skin impedance, as shown in Figure 4B. Figure 4B shows 150 independent and simultaneous measurements of mannitol skin permeability and skin impedance for six different enhancer formulations. The relationship between skin impedance and permeability to hydrophilic solutes confirms that the former can be used as a surrogate measure for the later. Skin conductance is quick and easy to obtain and does not require additional sample handling and analysis. 

Skin impedance measured in INSIGHT at 24 hours correlates very well with skin inulin permeability at steady states (Fig. 5). This reduces incubation times, as compared to FDCs. 

INSIGHT uses skin impedance to evaluate the efficacy of formulations in increasing skin permeability as against the use of a model permeant. As a result, there is no dependence of the physicochemical properties of the model permeant on the measured efficacy of the formulation. 

Figure 5 Plot of conductivity enhancement ratios (ERs) in INSIGHT at 24 hours versus permeability ERs in FDC for 12 enhancer formulations. A strong linear correlation indicates the validity of observations in INSIGHT when compared with those from traditional tools such as FDC. Abbreviations. INSIGHT, in vitro skin impedance guided high-throughput screening FDC, Franz diffusion cell.

Craane-van Hinsberg, W.H.M., et al. 1994. Iontophoresis of a model peptide across human skin in vitro Effects of iontophoresis protocol, pH and ionic strength on peptide flux and skin impedance. Pharm Res 11 1296. 

Bodde, H. E., Pechtold, L. A. R. M. and de Haan, F. H. N. A large scale, noninvasive in vivo screening of human skin barrier and water holding properties recording infrared spectra, TEWL, skin impedance and temperature. Pharmaceutical Research 9 S186, 1992. 

The lack of SC lipid bilayer alteration during iontophoresis is contrary to the conclusion drawn from published results involving skin impedance measurements [3]. In these experiments, as current was applied across the skin, the electrical impedance was measured as a function of temperature. At around 65 °C, a 100-fold decrease in the electrical resistance was observed, which corresponded to a solid-to-fluid phase change affecting the structure of SC bilayers, as observed using other techniques [13,15,30]. As the current density was increased from 13 to 130 pA/cm, the impedance decrease occurred at a lower temperature, suggesting a current-induced perturbation of the SC bilayer... 

Impedance spectroscopy (IS) is a measurement of the conductive and dielectric properties of electroactive systems over a wide range of frequencies. Its popularity and applicability has increased dramatically over the past 25 years with the advent of fast-response potentiostats and frequency response analyzers. Impedance spectroscopy has been applied extensively in electrochemistry, especially in battery and sensor research, and it has been used to study active transport in biological membranes. Skin impedance has also been investigated with IS, but many of these studies attempted to correlate impedance with hydration and provided no insight into the mechanism of charge transport. More recent studies have used IS to elucidate the pathways of ion transport through skin, with special emphasis on understanding the mechanism... 

The profound variability in the skin s Impedance is one of the primary problems in the application of impedance spectroscopy to the study of the skin. It is thus necessary to control or remove as many factors as possible that lead to the variability in skin impedance before useful information can be obtained from impedance measurements [9]. Several methods have been proposed that can be implemented to decrease the variability of impedance measurements. Such methods include the following ... 

Since irritants also influence the hydration state and the integrity of the skin, impedance spectroscopy provides a useful method for the quantification of skin irritant effects. The chief irritant studied has been sodium lauryl sulfate (SLS) [24-26]. Studies show that as the dose of SLS was increased, the amount of decrease in impedance was also increased [26]. By following the skin s impedance after the application of SLS, changes in the skin s conductivity showed up well before any visual signs of skin irritation were detectable [24]. In addition, it was demonstrated that exposure to SLS resulted in a gradual loss in the skin s barrier properties [24]. Finally, skin lotions have been shown to decrease the damage (as assessed by the degree the skin s impedance has decreased) caused to the skin by SLS. 

Archer, W., Kohli, R., Roberts, J. and Spencer, T. Skin Impedance Measurement. In R. Rietschel and T. Spencer, eds. Methods for Cutaneous Investigation. New York, Dekker,... 

Yamamoto, T. and Yamamoto, Y. The measurement principle for evaluating the performance of drugs and cosmetics by skin impedance. Med. Biol. Eng. Comput. 76 623, 1978. 

A pulsed depolarizing iontophoretic system has been developed by Advance Co. [26] that delivers a current of frequency 40 Hz and an on-off duty of 30% to deliver a significant amount of metoprolol into the blood without any observed skin irritation or erythema at the site of application. Okabe et al. [26] hypothesized that the high-frequency pulses provided low skin impedance in addition, the capacitance of the skin was restored to its initial state at the start of each pulse cycle. Chien et al. [89] reported that a sine waveform induced a faster hypoglycemic effect with insulin, with the peak at approximately 2 hours, than either a trapezoidal (7 hours) or a square waveform (12 hours) however, the duration of the hypoglycemia was also shorter (11 hours) compared with the other two waveforms [89]. 

Researchers have reported that, for impedance measurements on human skin under fixed-amplitude galvanostatic modulation, significant changes in skin properties were observed that could be attributed to the impedance measurement. The magnitude of the skin impedance varied from about 10 Ocm at high frequency to 100 fcOcm at low frequency. The perturbation amplitude was 0.1 mA on an exposed skin sample of 1 cm area. Explain the reasons for their observation and suggest an improved experimental protocol. 

Skinning Beginning superficial solidification (curing) of a reactive adhesive applied to an adherend. Skinning impedes or even prevents the wetting of the second adherend. Examples polyurethane, silicone adhesives. 

Silny, J., Rau, G. (1977). Messung des komplexen Hautwiderstandes [Measurement of complex skin impedance]. Biomedizinische Technik, 22, 409-410. 

The model to the left in Figure 10.3 is often used to model skin impedance. For instance, R may represent the deeper viable parts and the parallel R and C components represent the poorly conducting stratum corneum (SC). The model to the right may be used for tissue as shown in Figure 10.2. Then G models the extracellular electrolyte, C, the cell membranes, and R the intracellular resistance. Fixed component values in the two models can be found so that they have exactly the same impedance spectrum. 

Grimnes S. 1983b. Skin impedance and electro-osmosis in the human epidermis. Med Biol Eng Comput 21,739-749. 

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