Measurement and Thermodynamic Modeling of Lamotrigine Solubility in the Presence of Some Choline-Based Ionic Liquids

Choline chloride-based ionic liquids (ILs) have recently received a great deal of attention in many fields of science. In this regard, the mole fraction solubility data of lamotrigine (LTG) in the presence of three choline-based ILs were measured from 298.15 to 313.15 K. The LTG is known as an antiepileptic anticonvulsant or antiepileptic drug. This drug has few side effects in comparison to other drugs, and it has a slightly delayed onset of action because of the poor aqueous solubility of LTG (0.187 g/L at 298.15 K). The used ILs (choline glycinate [Ch] [Gly], choline alaninate [Ch] [Ala], and choline bitartrate [Ch] [Bitar]) increased the drug aqueous solubility. Based on the results of solubility studies, it was clear that [Ch] [Gly] has a more pronounced effect on LTG solubility enhancement as compared to the two other ILs. Also, in binary solvent systems (ILs and water), the solubility values increased with the rise of temperature. Analysis of the data showed that the solubility behavior was influenced by some properties, including the polarity, hydrogen bonds, cohesive energy density, and molecular structures. The measured data were fitted to some applicable models. The performance of the used models according to %ARD is e-NRTL (0.66%) > Wilson (4.04%) > Jouyban-Acree (5.59%) > Yalkowsky (5.73%) > Apelblat (5.78%). Additionally, the apparent thermodynamic properties of the dissolution process, including the Gibbs energy, enthalpy, and entropy, were calculated using the van't Hoff and Gibbs equations. The results showed that the dissolution process is an endothermic process and enthalpy-driven in all applied cosolvents. The solubility data for LTG in these neoteric green solvents can be widely used in the pharmaceutical sciences.