Exploring cytotoxicity of some choline-based deep eutectic solvents and their effect on the solubility of lamotrigine in aqueous media

Lamotrigine (LTG) is one of the well-known antiepileptic agents approved for the treatment of partial, primary, and secondary generalized tonic−clonic seizures, and it also is used for the treatment of seizures associated with Lennox−Gastaut syndrome. This drug has fewer side effects but the low aqueous solubility of LTG (0.189 g/L at 25 °C) is responsible for its delayed onset of action. The aim of the present study was to increase the solubility of LTG in the presence of a new generation of environmentally friendly solvents named deep eutectic solvents (DESs). The used DESs (choline chloride (ChCl)/ethylene glycol, urea and glycerol) enhanced the aqueous solubility of the drug. On the basis of solubility studies, it was found that ChCl/ethylene glycol has a more pronounced effect on increasing the solubility of LTG as compared to two other DESs. The measured data were fitted to the Jouyban – Acree, Apelblat – Jouyban – Acree, Van't Hoff – Jouyban – Acree, e-NRTL and Wilson models. On the other hand, one of the most important and fundamental considerations in pharmaceutical sciences is the selection of a low-toxic solvent. In this regard, the used co-solvent's cytotoxicity was studied and the results showed their moderate cytotoxicity on Lung cells. Furthermore, the apparent thermodynamic properties of the dissolution process are computed according to Van't Hoff and Gibbs equations.