Solubility modelling, solvent effect and preferential solvation of carbendazim in aqueous co-solvent mixtures of N,N-dimethylformamide, methanol, ethanol and n-propanol

Highlights: • Carbendazim solubility in four cosolvent mixtures was determined and correlated. • Solute-solvent and solvent-solvent interactions were investigated using KAT-LSER model. • Preferential solvation parameters were derived by IKBI method. -- Abstract: The equilibrium solubility of carbendazim in solvent mixtures of N,N-dimethylformamide (DMF, 1) + water (2), methanol (1) + water (2), ethanol (1) + water (2) and n-propanol (1) + water (2) were determined experimentally by using the saturation shake-flask method at the temperatures ranging from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). The solubility of carbendazim increased positively with increasing temperature and molar fraction of organic solvents in each binary system. The minimum solubility was observed in neat organic solvents. The solid phase was tested by X-ray power diffraction, which showed that no polymorphic transformation, solvate formation or crystal transition during entire experiments conclusively. The drug' solubility was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.95% for correlative studies. The preferential solvation parameters were derived from their thermodynamic solution properties with the inverse Kirkwood–Buff integrals. The preferential solvation parameters for DMF, methanol, ethanol or n-propanol (δx_1,3) were positive in the four solvent mixtures in intermediate and co-solvent-rich compositions, which indicated that carbendazim was preferentially solvated by co-solvent. It could act mainly as a Lewis acid interacting with proton-acceptor functional groups of the co-solvents. Temperature has a little effect on the preferential solvation magnitudes. Furthermore, the solvent effect was analyzed in the framework of linear solvation energy relationships by considering suitable combinations of solvent descriptors.