The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers

Takayuki Furuishi; Sara Taguchi; Siran Wang; Kaori Fukuzawa; Etsuo Yonemochi

doi:10.3390/pharmaceutics16030322

The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers

Pharmaceutics. 2024 Feb 26;16(3):322. doi: 10.3390/pharmaceutics16030322.

Authors

Takayuki Furuishi¹, Sara Taguchi¹, Siran Wang¹, Kaori Fukuzawa^{1

2}, Etsuo Yonemochi¹

Affiliations

¹ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
² Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

Abstract

In this study, we synthesized a family of novel ionic liquids (ILs) with meglumine (MGM) as cations and tartaric acid (TA), azelaic acid (AA), geranic acid (GA), and capric acid (CPA) as anions, using pharmaceutical additives via simple acid-base neutralization reactions. The successful synthesis was validated by attenuated total reflection-Fourier transform infrared (ATR-FTIR) and powder X-ray diffraction (PXRD). Thermal analysis using differential scanning calorimetry confirmed the glass transition temperature of MGM-ILs to be within the range of -43.4 °C--13.8 °C. We investigated the solubilization of 15 drugs with varying pKa and partition coefficient (log P) values using these ILs and performed a comparative analysis. Furthermore, we present MGM-IL as a new skin permeation enhancer for the drug model flurbiprofen (FRP). We confirmed that AA/MGM-IL improves the skin permeation of FRP through hairless mouse skin. Moreover, AA/MGM-IL enhanced drug skin permeability by affecting keratin rather than stratum corneum lipids, as confirmed by ATR-FTIR. To conclude, MGM-ILs exhibited potential as drug solubilizer and skin permeation enhancers of drugs.

Keywords: ionic liquid; meglumine; skin permeation enhancer; solubility; transdermal.

Grants and funding

This study was supported by the Hoshi University Grant-in-Aid for Leading Research Project grants in 2018; the OTC Self-Medication Promotion Foundation 2018; the Mochida Memorial Foundation for Medical and Pharmaceutical Research 2019–2020; and JSPS KAKENHI Grant Number 23K06220 (T.F.).