Solubility Behavior\nand Data Correlation of Edaravone\nin 12 Individual Solvents at Multiple Temperatures

Edaravone\nis an important free radical scavenger with significant\nefficacy in acute ischemic stroke (AIS) patients, which is essential\nin medical research. The solubility data of edaravone were measured\nby the static gravimetric method in 12 pure solvents (2-butanone,\n4-methyl-2-pentanone, hexane, 1,2-dichloroethane, 3-methyl-1-butanol,\nethyl lactate, dimethyl carbonate, butyl acetate, methyl acetate,\nisopropyl acetate, isobutyl acetate, and propyl acetate) from 283.15\nto 323.15 K and 101.2 kPa. The solubility of edaravone in all studied\nsolvents increased with the increase of temperature. At 298.15 K,\nthe solubility order of edaravone was: 1,2-dichloroethane (0.04168\nmol/mol) > ethyl lactate (0.03918 mol/mol) > 2-butanone (0.03722\nmol/mol)\n> 3-methyl-1-butanol (0.02609 mol/mol) > 4-methyl-2-pentanone\n(0.02432\nmol/mol) > methyl acetate (0.02372 mol/mol) > propyl acetate\n(0.02279\nmol/mol) > dimethyl carbonate (0.02011 mol/mol) > butyl acetate\n(0.01953\nmol/mol) > isobutyl acetate (0.01419 mol/mol) > isopropyl acetate\n(0.01621 mol/mol) > hexane (0.0005202 mol/mol). The Hansen solubility\nparameters (HSPs) were utilized to assess the solvents’ capability\nand to elucidate their ability to dissolve edaravone. The data obtained\nare partially in agreement with the analyses of the HSPs. The main\nfactors influencing the solubility behavior included the empirical\nsolvent polarity parameters (<i>E</i><sub>T</sub>(30)),\nhydrogen bonding, and cohesive energy density. It was found that the\nmost important factor affecting the solubility of edaravone was the\npolarity of the solvent. Three solubility fitting models were used\nto correlate the experimental mole fraction solubility data, including\nthe modified Apelblat model, the NRTL model, and the UNIQUAC model.\nAt the same time, the model parameters and data deviation values were\ncalculated. The results showed that the modified Apelblat model had\nbetter correlation results. Furthermore, mixing thermodynamic characteristics\nof edaravone in selected solvents were calculated by the NRTL model,\nwhich revealed that the mixing process was spontaneous and entropy-driven.\nThe aim of this study was to supplement the solubility data of edaravone\nin pure solvents and provide data support for the production of its\ncrystals with higher medicinal values.