Effect of novel surfactant protic ethanolamine based ionic liquids on the aqueous solubility and thermodynamic properties of acetaminophen

Mohammad Bagheri, Hemayat Shekaari, Masumeh Mokhtarpour, Aysan Alavi, Sara Dorosti, Mika Sillanpää, Ky Nguyen

Research output: Contribution to journalArticlepeer-review


The solubility of poorly soluble drugs in aqueous media remains an obstacle in the pharmaceutical development process. Ionic liquids (ILs), with their remarkable solvent properties, have gained considerable attention as potential solubility enhancers for such drugs. In this context, surfactant protic ethanolamine-based ILs have emerged as a particularly promising class of compounds due to their unique dual functionality. This study explores the significant role of these novel solvents in improving drug solubility, focusing on their potential applications in pharmaceutical formulations. Acetaminophen (ACP), a widely used analgesic and antipyretic drug, often encounters solubility limitations that hinder its effective pharmaceutical applications. In the past few years, there has been a growing recognition of the potential of ILs (ionic liquids) as effective solvents. They offer promising prospects for enhancing the solubility of pharmaceutical substances in water-based solutions. This study investigates the enhancement of ACP solubility through the utilization of ILs. The solubilization behavior of ACP in the attendance of mono, bis and tris-(2-hydroxyethylammonium) octanoate systems is explored, highlighting the significant impact of different number of hydroxyethyl groups combinations on its solubility profile. Experimental results reveal that these ILs exhibit a remarkable ability to improve the solubility of ACP, making them attractive candidates for pharmaceutical formulations. The mechanisms underlying this enhancement are discussed, encompassing factors such as the ion-specific interactions, polarity, and hydrogen bonding capabilities of ionic liquids. Furthermore, the potential implications of utilizing ILs for enhancing the bioavailability and formulation versatility of ACP are considered. To accurately correlate the solubility data, various thermodynamic models were employed. Furthermore, to examine the observable thermodynamic characteristics of dissolution in the studied systems Van't Hoff and Gibbs equations were used. The findings indicated that the dissolution process in all co-solvents used was characterized by an endothermic nature and driven by enthalpy.

Original languageEnglish
Article number124999
JournalJournal of Molecular Liquids
Publication statusPublished - 15 Jul 2024


  • Acetaminophen
  • Activity coefficient model
  • Ethanolamine
  • Ionic liquid
  • Solubility

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Materials Chemistry


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