The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine

<b>Background/Objectives</b>: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible al...

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Main Authors: Feria Hasanpour, Mária Budai-Szűcs, Anita Kovács, Rita Ambrus, Orsolya Jójárt-Laczkovich, Boglárka Szalai, Branimir Pavlić, Péter Simon, Levente Törteli, Szilvia Berkó
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/3/324
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author Feria Hasanpour
Mária Budai-Szűcs
Anita Kovács
Rita Ambrus
Orsolya Jójárt-Laczkovich
Boglárka Szalai
Branimir Pavlić
Péter Simon
Levente Törteli
Szilvia Berkó
author_facet Feria Hasanpour
Mária Budai-Szűcs
Anita Kovács
Rita Ambrus
Orsolya Jójárt-Laczkovich
Boglárka Szalai
Branimir Pavlić
Péter Simon
Levente Törteli
Szilvia Berkó
author_sort Feria Hasanpour
collection DOAJ
description <b>Background/Objectives</b>: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible alternative to conventional lidocaine formulations, improving the dermal permeation and therapeutic efficacy. <b>Methods:</b> The lidocaine base was dissolved in a hydrophilic NADES system composed of choline chloride and citric acid, facilitating enhanced solubility, likely through new molecular interactions. Then, pH-adjusted hydrogels were formulated and optimized by employing a 3<sup>2</sup> full factorial design. Raman and nuclear magnetic resonance (NMR) spectroscopy were applied to evaluate the stability of lidocaine in the optimal formulation. The biopharmaceutical properties were investigated using in vitro drug release and skin permeation studies. In vivo tests assessed physiological skin parameters such as the hydration and transepidermal water loss. <b>Results:</b> The developed NADES-containing hydrogel significantly improved the solubility and stability of lidocaine. Skin permeation studies demonstrated enhanced dermal permeation compared with conventional hydrogel and ointment. These improvements, namely the enhanced solubility of lidocaine in the formulation and its increased permeation, were attributed to the dual effect of the NADES. <b>Conclusions:</b> NADES-containing hydrogels represent a promising green technology for formulating lidocaine-containing dermal preparations. This approach offers a biocompatible, natural-based alternative that can enhance the bioavailability and efficacy of topical anesthetics.
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spelling doaj-art-fd0111c9087f445eb9db7faced0cec772025-08-20T03:43:10ZengMDPI AGPharmaceutics1999-49232025-03-0117332410.3390/pharmaceutics17030324The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing LidocaineFeria Hasanpour0Mária Budai-Szűcs1Anita Kovács2Rita Ambrus3Orsolya Jójárt-Laczkovich4Boglárka Szalai5Branimir Pavlić6Péter Simon7Levente Törteli8Szilvia Berkó9Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, HungaryFaculty of Technology, University of Novi Sad, Blvd. Cara Lazara 1, 21000 Novi Sad, SerbiaInstitute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, Hungary<b>Background/Objectives</b>: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible alternative to conventional lidocaine formulations, improving the dermal permeation and therapeutic efficacy. <b>Methods:</b> The lidocaine base was dissolved in a hydrophilic NADES system composed of choline chloride and citric acid, facilitating enhanced solubility, likely through new molecular interactions. Then, pH-adjusted hydrogels were formulated and optimized by employing a 3<sup>2</sup> full factorial design. Raman and nuclear magnetic resonance (NMR) spectroscopy were applied to evaluate the stability of lidocaine in the optimal formulation. The biopharmaceutical properties were investigated using in vitro drug release and skin permeation studies. In vivo tests assessed physiological skin parameters such as the hydration and transepidermal water loss. <b>Results:</b> The developed NADES-containing hydrogel significantly improved the solubility and stability of lidocaine. Skin permeation studies demonstrated enhanced dermal permeation compared with conventional hydrogel and ointment. These improvements, namely the enhanced solubility of lidocaine in the formulation and its increased permeation, were attributed to the dual effect of the NADES. <b>Conclusions:</b> NADES-containing hydrogels represent a promising green technology for formulating lidocaine-containing dermal preparations. This approach offers a biocompatible, natural-based alternative that can enhance the bioavailability and efficacy of topical anesthetics.https://www.mdpi.com/1999-4923/17/3/324dermal permeationhydrogellidocainelocal anestheticsnatural deep eutectic solvents (NADESs)
spellingShingle Feria Hasanpour
Mária Budai-Szűcs
Anita Kovács
Rita Ambrus
Orsolya Jójárt-Laczkovich
Boglárka Szalai
Branimir Pavlić
Péter Simon
Levente Törteli
Szilvia Berkó
The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
Pharmaceutics
dermal permeation
hydrogel
lidocaine
local anesthetics
natural deep eutectic solvents (NADESs)
title The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
title_full The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
title_fullStr The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
title_full_unstemmed The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
title_short The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
title_sort role of natural deep eutectic solvents in a hydrogel formulation containing lidocaine
topic dermal permeation
hydrogel
lidocaine
local anesthetics
natural deep eutectic solvents (NADESs)
url https://www.mdpi.com/1999-4923/17/3/324
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