Effect of mono, di, tri ethanolamine lactate ionic liquids on the solubility of acetaminophen: Experimental measurement and correlation

Solubility is one of the most important physicochemical properties in the discovery and development of drugs and adding a co-solvent to an aqueous solution for further designing drug formation is the most widely used method in the pharmaceutical industry. In recent years, protic ionic liquids (PILs) as a new low-cost and an environmentally friendly class of green solvents have been used to overcome drug solubility issues. In this research work, the effect of some PILs containing 2-hydroxyethylammonium, bis (2-hydroxyethyl)ammonium, and tris(2-hydroxyethyl)ammonium cations and lactate anion have been investigated for acetaminophen (ACP) solubility at temperature ranges (298.15 to 313.15) K. The results show that ACP solubility increases with increasing PIL concentration and at higher temperatures and that PILs containing tris(2-hydroxyethyl)ammonium lactate have a greater impact on ACP solubility. The obtained solubility data were fitted by the e-NRTL and Wilson models which e-NRTL model is more consistent with experimental data. Finally, by applying the Gibbs and van't Hoff equations, the apparent dissolution thermodynamic functions such as enthalpy, Gibbs free energy, and entropy have been estimated. The results indicate that ACP dissolution processes in the investigated systems are endothermic. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Solubility is a crucial property in drug discovery and development, and adding a co-solvent to aqueous solutions is a widely used method in the pharmaceutical industry. Protic ionic liquids (PILs) have emerged as a low-cost and environmentally friendly solvent for improving drug solubility. This research investigated the effect of PILs containing specific cations and anions on the solubility of acetaminophen (ACP), and found that higher concentrations and temperatures of PILs led to increased ACP solubility. The e-NRTL model was found to be more accurate in fitting the solubility data. Thermodynamic functions of ACP dissolution, such as enthalpy, Gibbs free energy, and entropy, were estimated using the Gibbs and van't Hoff equations, revealing an endothermic dissolution process.