Abstract
Recently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15-313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat-Jouyban-Acree > Van't Hoff-Jouyban-Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van't Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA < MEAP < MEAL. These findings indicated that these PILs had low to moderate toxicity. It is noteworthy that the functional groups of the anions were not the only determinant factor of the cytotoxicity. Other factors encompassing concentration, exposure time, and cell line characteristics also had significant effects.