Solubility Behavior and Data Correlation of Edaravone in 12 Individual Solvents at Multiple Temperatures

Abstract

Edaravone is an important free radical scavenger with significant efficacy in acute ischemic stroke (AIS) patients, which is essential in medical research. The solubility data of edaravone were measured by the static gravimetric method in 12 pure solvents (2-butanone, 4-methyl-2-pentanone, hexane, 1,2-dichloroethane, 3-methyl-1-butanol, ethyl lactate, dimethyl carbonate, butyl acetate, methyl acetate, isopropyl acetate, isobutyl acetate, and propyl acetate) from 283.15 to 323.15 K and 101.2 kPa. The solubility of edaravone in all studied solvents increased with the increase of temperature. At 298.15 K, the solubility order of edaravone was: 1,2-dichloroethane (0.04168 mol/mol) > ethyl lactate (0.03918 mol/mol) > 2-butanone (0.03722 mol/mol) > 3-methyl-1-butanol (0.02609 mol/mol) > 4-methyl-2-pentanone (0.02432 mol/mol) > methyl acetate (0.02372 mol/mol) > propyl acetate (0.02279 mol/mol) > dimethyl carbonate (0.02011 mol/mol) > butyl acetate (0.01953 mol/mol) > isobutyl acetate (0.01419 mol/mol) > isopropyl acetate (0.01621 mol/mol) > hexane (0.0005202 mol/mol). The Hansen solubility parameters (HSPs) were utilized to assess the solvents’ capability and to elucidate their ability to dissolve edaravone. The data obtained are partially in agreement with the analyses of the HSPs. The main factors influencing the solubility behavior included the empirical solvent polarity parameters (E_T(30)), hydrogen bonding, and cohesive energy density. It was found that the most important factor affecting the solubility of edaravone was the polarity of the solvent. Three solubility fitting models were used to correlate the experimental mole fraction solubility data, including the modified Apelblat model, the NRTL model, and the UNIQUAC model. At the same time, the model parameters and data deviation values were calculated. The results showed that the modified Apelblat model had better correlation results. Furthermore, mixing thermodynamic characteristics of edaravone in selected solvents were calculated by the NRTL model, which revealed that the mixing process was spontaneous and entropy-driven. The aim of this study was to supplement the solubility data of edaravone in pure solvents and provide data support for the production of its crystals with higher medicinal values.