Assessment of solid–liquid equilibrium behavior of naphazoline nitrate in ten pure solvents by molecular simulation and thermodynamic analysis

Abstract

A laser monitoring method was used to determine the mole-fraction solubility of naphazoline nitrate (NPZN) in ten mono-solvents namely “methanol (MeOH), ethylene glycol monomethyl ether (EGME), ethanol (EtOH), ethylene glycol monoethyl ether (EGEE), n-propanol (n-PrOH), ethylene glycol monopropyl ether (EGPE), isopropanol (i-PrOH), ethylene glycol (EG), ethylene glycol monobutyl ether (EGBE) and N,N-dimethylformamide (DMF)” at (278.15 ∼ 323.15) K and 0.1 MPa. Results suggested that NPZN solubility values exhibited an increasing trend at investigated temperature ranges. Simultaneously, experimental solubility of NPZH had a general order of “DMF > EGME > EG > MeOH > EGEE > EGPE > EtOH > EGBE > n-PrOH > i-PrOH”. Hirshfeld surface was employed to analyze and quantize the intermolecular interaction of NPZN during the crystal construction process. The impact of solute–solvent interaction on NPZN solubility was investigated by calculating the solvation free energies of solute in selected solvents through molecular dynamic (MD) simulation. It turned out that NPZN solubility was positively associated with solute–solvent interaction. Solubility values of NPZN were correlated by Wilson, NRTL, NRTL-SAC as well as UNIQUAC model, corresponding fitting accuracies of different model were in variation based on various root mean squared deviation (RMSD) and average relative deviation (ARD). The computational results indicated that UNIQUAC model performed the highest accuracy in correlation of experimental solubility. Finally, thermodynamic properties of dissolution process and mixing process were investigated by UNIQUAC model in this research work. The existences of negative Gibbs energy changes and positive entropy changes were observed, which suggested that the dissolution process and mixing process were always spontaneous and entropy-increasing.