Assessment of skin permeability to topically applied drugs by skin impedance and admittance

Schwingenschuh, Simon; Scharfetter, Hermann; Martinsen, Ørjan G.; Boulgaropoulos, Beate; Augustin, Thomas; Tiffner, Katrin I.; Dragatin, Christian; Raml, Reingard; Hoefferer, C.; Prandl, Eva; Sinner, Frank; Hajnsek, Martin

doi:10.1088/1361-6579/aa904e

Cited by 7 publications

(9 citation statements)

References 28 publications

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“…At present, the EIS method has been widely used in some clinical studies, such as in transdermal drug delivery by measuring skin impedance changes to determine the absorption of drug delivery, in monitoring of the late recovery of osseointegration in hearing therapy, and in studying muscle state [ 11 ]. Besides the EIS method, another method which means skin impedance measured at a single low frequency, such as f = 100 Hz or f = 1000 Hz, has also been adopted in research of the relationship between skin impedance and skin permeability [ 17 , 22 ].…”

Section: Methods and System For Impedance Measurementmentioning

confidence: 99%

“…There are some commercially available devices for performing EIS methods, like Gamry (Warminster, PA, USA) and Autolab (Herisau, Switzerland) [ 17 , 64 ], which perform well in accuracy and efficiency. However, these instruments are too large to be used for portable application.…”

Section: Methods and System For Impedance Measurementmentioning

confidence: 99%

“…A wet electrode is more like a nonpolarizable electrode and can be divided into two types as well: pre-gelled electrode and electrolyte electrode [ 17 , 44 ]. The pre-gelled electrode, which is generally referred to as the disposable pre-gelled Ag/AgCl wet electrode, is more convenient to use and is preferred in electrophysiological signal detection due to its low cost, good fitting with skin and nice conductivity.…”

Section: Electrodes For Skin Impedance Measurementmentioning

confidence: 99%

“…Skin permeability characterization, especially in the assessment of the penetration promotion effect, is one of the most important applications of skin impedance. The relationship between skin permeability and skin impedance has been studied by various methods [ 11 , 14 , 15 , 16 , 17 ], and much effort has been put towards proving the relationship between skin penetration and skin impedance, especially for the impedance of SC. References [ 18 , 19 ] demonstrated that humidity has a great influence on skin impedance because it changes the hydration state of SC.…”

Section: Introductionmentioning

confidence: 99%

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Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration Application

Wang

Zhao

et al. 2018

Biosensors

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Due to advances in telemedicine, mobile medical care, wearable health monitoring, and electronic skin, great efforts have been directed to non-invasive monitoring and treatment of disease. These processes generally involve disease detection from interstitial fluid (ISF) instead of blood, and transdermal drug delivery. However, the quantitative extraction of ISF and the level of drug absorption are greatly affected by the individual’s skin permeability, which is closely related to the properties of the stratum corneum (SC). Therefore, measurement of SC impedance has been proposed as an appropriate way for assessing individual skin differences. In order to figure out the current status and research direction of human SC impedance detection, investigations regarding skin impedance measurement have been reviewed in this paper. Future directions are concluded after a review of impedance models, electrodes, measurement methods and systems, and their applications in treatment. It is believed that a well-matched skin impedance model and measurement method will be established for clinical and point-of care applications in the near future.

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Section: Methods and System For Impedance Measurementmentioning

confidence: 99%

Section: Methods and System For Impedance Measurementmentioning

confidence: 99%

Section: Electrodes For Skin Impedance Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration Application

Wang

Zhao

et al. 2018

Biosensors

View full text Add to dashboard Cite

show abstract

“…Under low frequency conditions (100 Hz~1000 Hz), skin impedance can better reflect its penetration. The smaller the impedance of skin becomes, the greater the penetration of skin becomes [ 11 , 12 , 13 ]. Traditionally, skin permeability evaluation, which is realized by impedance detected at a certain frequency based on macro-electrode, has the disadvantages of large measurement error, low sensitivity, and difficulty in integration [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Flexible Interdigital Electrode Used in Skin Penetration Promotion and Evaluation with Electroporation and Reverse Iontophoresis Synergistically

Zhao

Wang

et al. 2018

Sensors

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Skin penetration is related to efficiencies of drug delivery or ISF extraction. Normally, the macro-electrode is employed in skin permeability promotion and evaluation, which has the disadvantages of easily causing skin damage when using electroporation or reverse iontophoresis by alone; furthermore, it has large measurement error, low sensitivity, and difficulty in integration. To resolve these issues, this paper presents a flexible interdigital microelectrode for evaluating skin penetration by sensing impedance and a method of synergistical combination of electroporation and reverse iontophoresis to promote skin penetration. First, a flexible interdigital microelectrode was designed with a minimal configuration circuit of electroporation and reverse iontophoresis for future wearable application. Due to the variation of the skin impedance correlated with many factors, relative changes of it were recorded at the end of supply, different voltage, or constant current, times, and duration. It is found that the better results can be obtained by using electroporation for 5 min then reverse iontophoresis for 12 min. By synergistically using electroporation and reverse iontophoresis, the penetration of skin is promoted. The results tested in vivo suggest that the developed microelectrode can be applied to evaluate and promote the skin penetration and the designed method promises to leave the skin without damage. The electrode and the method may be beneficial for designing noninvasive glucose sensors.

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Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion

et al. 2020

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Purpose Dermal open flow microperfusion (dOFM) has previously demonstrated its utility to assess the bioequivalence (BE) of topical drug products in a clinical study. We aimed to characterize the sources of variability in the dermal pharmacokinetic data from that study. Methods Exploratory statistical analyses were performed with multivariate data from a clinical dOFM-study in 20 healthy adults evaluating the BE, or lack thereof, of Austrian test (T) and U.S. reference (R) acyclovir cream, 5% products. Results The overall variability of logAUC values (CV: 39% for R and 45% for T) was dominated by inter-subject variability (R: 82%, T: 91%) which correlated best with the subject’s skin conductance. Intra-subject variability was 18% (R) and 9% (T) of the overall variability; skin treatment sites or methodological factors did not significantly contribute to that variability. Conclusions Inter-subject variability was the major component of overall variability for acyclovir, and treatment site location did not significantly influence intra-subject variability. These results support a dOFM BE study design with T and R products assessed simultaneously on the same subject, where T and R treatment sites do not necessarily need to be next to each other. Localized variation in skin microstructure may be primarily responsible for intra-subject variability.

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Assessment of skin permeability to topically applied drugs by skin impedance and admittance

Cited by 7 publications

References 28 publications

Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration Application

Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration Application

A Flexible Interdigital Electrode Used in Skin Penetration Promotion and Evaluation with Electroporation and Reverse Iontophoresis Synergistically

Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion

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