Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis

<b>Background/Objectives</b>: Reverse iontophoresis (R-IP) is a technology that transdermally delivers components from inside the body to outside the body using electroosmotic flow (EOF) generated by applying a low electric current through the skin. It has attracted attention as a non-in...

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Main Authors: Rie Yamauchi, Shuji Ohno, Yasuko Obata
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/5/677
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author Rie Yamauchi
Shuji Ohno
Yasuko Obata
author_facet Rie Yamauchi
Shuji Ohno
Yasuko Obata
author_sort Rie Yamauchi
collection DOAJ
description <b>Background/Objectives</b>: Reverse iontophoresis (R-IP) is a technology that transdermally delivers components from inside the body to outside the body using electroosmotic flow (EOF) generated by applying a low electric current through the skin. It has attracted attention as a non-invasive sampling method for therapeutic drug monitoring (TDM). The purpose of this study was to determine whether urea and Tween 80 effectively enhance drug extraction from beneath the skin using R-IP. <b>Methods</b>: An in vitro drug extraction test using hairless mouse skin and R-IP was performed with a 3-chamber Franz cell and Ag|AgCl electrodes by applying a constant current (0.25 mA/cm<sup>2</sup>) for 6 h. Acetaminophen was chosen as the model drug, and its solution (30, 100, or 300 μg/mL) was placed in the subdermal compartment. The pH of both the electrode and subdermal compartment solutions was maintained at 7.4. <b>Results</b>: Acetaminophen was gradually extracted into the electrode compartment in a concentration-dependent manner and was more abundant in the cathode compartment than in the anode compartment. In addition, urea significantly promoted drug extraction, particularly on the cathode side, and a linear relationship was observed between the subdermal concentration and extracted amount. This effect is likely due to skin hydration caused by urea, which enhances EOF generation in the skin. Conversely, Tween 80 had no effect on drug extraction. <b>Conclusions</b>: R-IP combined with urea is expected to not only shorten the treatment time but also enable its application to drugs with low concentrations in blood.
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spelling doaj-art-a21a37ea366e4db88b0d6dfae3873c032025-08-20T02:34:01ZengMDPI AGPharmaceutics1999-49232025-05-0117567710.3390/pharmaceutics17050677Effect of Urea on Drug Extraction Efficiency in Reverse IontophoresisRie Yamauchi0Shuji Ohno1Yasuko Obata2Division of Pharmaceutical Education and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, JapanDivision of Pharmaceutical Education and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, JapanLaboratory of Pharmaceutical Science and Technology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan<b>Background/Objectives</b>: Reverse iontophoresis (R-IP) is a technology that transdermally delivers components from inside the body to outside the body using electroosmotic flow (EOF) generated by applying a low electric current through the skin. It has attracted attention as a non-invasive sampling method for therapeutic drug monitoring (TDM). The purpose of this study was to determine whether urea and Tween 80 effectively enhance drug extraction from beneath the skin using R-IP. <b>Methods</b>: An in vitro drug extraction test using hairless mouse skin and R-IP was performed with a 3-chamber Franz cell and Ag|AgCl electrodes by applying a constant current (0.25 mA/cm<sup>2</sup>) for 6 h. Acetaminophen was chosen as the model drug, and its solution (30, 100, or 300 μg/mL) was placed in the subdermal compartment. The pH of both the electrode and subdermal compartment solutions was maintained at 7.4. <b>Results</b>: Acetaminophen was gradually extracted into the electrode compartment in a concentration-dependent manner and was more abundant in the cathode compartment than in the anode compartment. In addition, urea significantly promoted drug extraction, particularly on the cathode side, and a linear relationship was observed between the subdermal concentration and extracted amount. This effect is likely due to skin hydration caused by urea, which enhances EOF generation in the skin. Conversely, Tween 80 had no effect on drug extraction. <b>Conclusions</b>: R-IP combined with urea is expected to not only shorten the treatment time but also enable its application to drugs with low concentrations in blood.https://www.mdpi.com/1999-4923/17/5/677reverse iontophoresisnon-invasive drug monitoringacetaminophenureaextraction enhancerskin hydration
spellingShingle Rie Yamauchi
Shuji Ohno
Yasuko Obata
Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
Pharmaceutics
reverse iontophoresis
non-invasive drug monitoring
acetaminophen
urea
extraction enhancer
skin hydration
title Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
title_full Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
title_fullStr Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
title_full_unstemmed Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
title_short Effect of Urea on Drug Extraction Efficiency in Reverse Iontophoresis
title_sort effect of urea on drug extraction efficiency in reverse iontophoresis
topic reverse iontophoresis
non-invasive drug monitoring
acetaminophen
urea
extraction enhancer
skin hydration
url https://www.mdpi.com/1999-4923/17/5/677
work_keys_str_mv AT rieyamauchi effectofureaondrugextractionefficiencyinreverseiontophoresis
AT shujiohno effectofureaondrugextractionefficiencyinreverseiontophoresis
AT yasukoobata effectofureaondrugextractionefficiencyinreverseiontophoresis