Characterization and drug solubilization of arginine-based ionic liquids - Impact of counterions and stoichiometry

Siran Wang; Qihui Xu; Takayuki Furuishi; Kaori Fukuzawa; Etsuo Yonemochi

doi:10.1016/j.ijpharm.2024.124228

Characterization and drug solubilization of arginine-based ionic liquids - Impact of counterions and stoichiometry

Int J Pharm. 2024 May 12:659:124228. doi: 10.1016/j.ijpharm.2024.124228. Online ahead of print.

Authors

Siran Wang¹, Qihui Xu¹, Takayuki Furuishi², Kaori Fukuzawa³, Etsuo Yonemochi⁴

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 Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: t-furuishi@hoshi.ac.jp.
³ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Japan.
⁴ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: e-yonemochi@hoshi.ac.jp.

PMID: 38744415
DOI: 10.1016/j.ijpharm.2024.124228

Abstract

Ionic liquids (ILs) exhibit very diverse physicochemical properties, such as non-volatility, stability, and miscibility, which render them excellent candidate excipients for multi-purpose use. Six novel arginine (Arg)-based ILs were obtained using a one-step ultrasound method. Salt formation was confirmed by Fourier-transform infrared (FTIR), Raman, and nuclear magnetic resonance (NMR) spectroscopies. Moreover, the effects of anions and molar ratio on the molecular states and thermal properties of Arg-ILs were investigated. In addition, the solubilization of drugs with different pKa and LogP values was attempted using Arg-ILs consisting of asparagine, proline, octanoic acid, and malic acid, respectively, and a comparative study was performed. Furthermore, the interaction mode between the drugs and ILs was determined by FTIR and Raman spectroscopy. Presumably, partial interaction between the component of ILs and drugs such as ofloxacin and valsartan occurred, whereas flurbiprofen and isosorbide mononitrate were dispersed in the viscous IL. The development of strategies for the application of ILs as solubilizers or carriers of active pharmaceutical ingredients is an extremely promising and wide avenue of research.

Keywords: Arginine; Ionic liquids; Molecular state; Oligomeric ionic liquids; Solubilization.