Diflufenican equilibrium solubilities when dissolved in a series of cosolvent mixtures of (ethanol + water), (ethylene glycol, EG + water), (propylene glycol, PG + water), and (N,N-dimethyl formamide, DMF + water) were determined and analyzed by the isothermal saturation method from 278.15 to 323.15 K at an ambient pressure of 101.2 kPa. Four pure organic solvents including ethanol, EG, PG, and DMF showed great dissolving capacity in various aqueous cosolvency systems and their solubility (in mole fraction) order was as follows: DMF (2.983 × 10–3, 323.15 K) > PG (2.454 × 10–4, 323.15 K) > ethanol (1.129 × 10–4, 323.15 K) > EG (7.490 × 10–5, 323.15 K) > water (1.042 × 10–6, 323.15 K). Among many factors, temperature and solvent water content were the two variables that had the greatest impact on diflufenican solubility. Taking temperature as an example, the monotonicity of the drug mole fraction curve was in step with the changing trend of the temperature. On the contrary, the monotonicity of the dissolved amount was in an antagonistic relationship with the trend of the water content of the solvent. It was found that the maximum solubility (2.983 × 10–3, 323.15 K) was observed in the DMF + water system. X-ray powder diffraction (XPRD) was used to characterize the diflufenican crystal samples to eliminate the possibility of chemical reaction and formation of solvates when diflufenican is mixed with various solvents. Thermodynamic mathematical models (Jouyban–Acree model, Van’t Hoff–Jouyban–Acree model, and the modified Apelblat–Jouyban–Acree model) were used to analyze and correlate the equilibrium diflufenican solubilities in the four cosolvent mixtures. The largest RAD and RMSD obtained from the three cosolvency models were 2.83 × 10–2 and 1.15 × 10–5 based on the correlation results, respectively. All models provided a good description of the solubility behaviors of diflufenican and the Jouyban–Acree model gave the best fitting results. The entire data obtained in this work are helpful for purification and recrystallization processes.
Electrostatic characteristics of acidity and basicity of the diflufenican molecule were uncovered by examining the Hirshfeld surface and the electrostatic potential surface, respectively. When it comes to nucleophilic and electrophilic assault, the >NH, =O, and -O- groups are where it is at. Diflufenican-solvent interactions were shown using an independent gradient model based on Hirshfeld partition analysis. Under 101.2 kPa, the isothermal saturation technique was used to experimentally obtain the diflufenican solubility in mixtures of isopropanol/methanol + water and ethyl acetate + ethanol across the temperature range from 278.15 to 323.15 K. Diflufenican was more soluble in ethyl acetate + ethanol blends than alcohol + water blends at the same temperature and cosolvent composition. Maximum relative average deviation of 9.57 percent was obtained using the Jouyban-Acree and modified van't Hoff-Jouyban-Acree models of correlation. The literature-reported solubility of diflufenican in ethylene glycol (EG), ethanol, propylene glycol (PG), and N , N -dimethylformamide (DMF) + water, as well as our determined in ethyl acetate + ethanol and methanol/isopropanol + water at 298.15 K, were all investigated using an extended Hildebrand solubility parameter approach. The local mole fractions of diflufenican in the seven solutions were also investigated using the inverse Kirkwood-Buff integrals technique. Preferential solvation of diflufenican by PG, ethanol, DMF, methanol, and isopropanol in aqueous solutions and by ethyl acetate in ethyl acetate + ethanol solutions was observed. Diflufenican in aqueous EG mixes was not preferentially solvated by EG. Results and discussion of the enthalpy–entropy compensation features of dissolution were reached.
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