Gabapentin, as an anticonvulsant is commonly prescribed off-label to treat neuropathic pain. Gabapentin is classified as a low-permeability drug in the gastrointestinal tract. To address this challenge, various optimization strategies have been explored. Surface-active ionic liquids (SAILs), combine surfactant and ionic liquid characteristics and offer potential as permeability enhancers. This study examines the interplay between gabapentin and ethanolamine-based SAILs in aqueous solutions to evaluate their potential for improving gabapentin’s drug-related properties. For this purpose, density, speed of sound, and electrical conductivity of gabapentin in water and aqueous (2-hydroxyethyl)ammonium Stearate, [2-HEA][St], bis(2-hydroxyethyl) ammonium stearate, [BHEA][St], and tris(2-hydroxyethyl) ammonium stearate, [THEA][St], were measured over a varied temperature range. The apparent molar volumes, <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="10765_2025_3589_Article_IEq1.gif" Format="GIF" Height="19" Rendition="HTML" Resolution="72" Type="Linedraw" Width="21" /> </InlineMediaObject> <EquationSource Format="TEX">$V_{\varphi }$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>V</mi> <mi>φ</mi> </msub> </math></EquationSource> </InlineEquation>, and apparent molar isentropic compressibility, <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="10765_2025_3589_Article_IEq2.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="20" /> </InlineMediaObject> <EquationSource Format="TEX">$\kappa_{\varphi }$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>κ</mi> <mi>φ</mi> </msub> </math></EquationSource> </InlineEquation>, were calculated and fitted by the Masson equation. The structural organization facilitated by gabapentin in the presence of SAILs has been substantiated. This interaction promotes enhanced hydrophobic hydration and various intermolecular interactions, which collectively contribute to improved bulk compressibility properties. The findings indicate that [THEA][St] demonstrates the lowest critical micelle concentration (CMC) value [1.0203 (mol·m−3) for [THEA][St] in water and 0.5401 (mol·m−3) in 0.0500 mol·kg−1 aqueous gabapentin solution] compared to the other studied SAILs. This suggests that the presence of [THEA][St] enhances the interaction with the gabapentin drug, making it the most favorable option for improving gabapentin drug-related properties. Analysis of the COSMO results indicates that as the molecular size increases, as shown by the expansion of surface area and volume, the solvation properties of the molecules generally improve. Graphical Abstract

Micellization and Thermodynamic Behavior of Surface-Active Ionic Liquids Based on 2-Hydroxyethylammonium Stearate in the Presence of Gabapentin

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发表日期：

2025年6月30日

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Mohammad Bagheri Hokm Abad,
Hemayat Shekaari,
Masumeh Mokhtarpour,
Behrang Golmohammadi

摘要

Gabapentin, as an anticonvulsant is commonly prescribed off-label to treat neuropathic pain. Gabapentin is classified as a low-permeability drug in the gastrointestinal tract. To address this challenge, various optimization strategies have been explored. Surface-active ionic liquids (SAILs), combine surfactant and ionic liquid characteristics and offer potential as permeability enhancers. This study examines the interplay between gabapentin and ethanolamine-based SAILs in aqueous solutions to evaluate their potential for improving gabapentin’s drug-related properties. For this purpose, density, speed of sound, and electrical conductivity of gabapentin in water and aqueous (2-hydroxyethyl)ammonium Stearate, [2-HEA][St], bis(2-hydroxyethyl) ammonium stearate, [BHEA][St], and tris(2-hydroxyethyl) ammonium stearate, [THEA][St], were measured over a varied temperature range. The apparent molar volumes, $V_{\varphi }$ $V_{φ}$ , and apparent molar isentropic compressibility, $\kappa_{\varphi }$ $κ_{φ}$ , were calculated and fitted by the Masson equation. The structural organization facilitated by gabapentin in the presence of SAILs has been substantiated. This interaction promotes enhanced hydrophobic hydration and various intermolecular interactions, which collectively contribute to improved bulk compressibility properties. The findings indicate that [THEA][St] demonstrates the lowest critical micelle concentration (CMC) value [1.0203 (mol·m⁻³) for [THEA][St] in water and 0.5401 (mol·m⁻³) in 0.0500 mol·kg⁻¹ aqueous gabapentin solution] compared to the other studied SAILs. This suggests that the presence of [THEA][St] enhances the interaction with the gabapentin drug, making it the most favorable option for improving gabapentin drug-related properties. Analysis of the COSMO results indicates that as the molecular size increases, as shown by the expansion of surface area and volume, the solvation properties of the molecules generally improve.

Graphical Abstract