Combined Experimental and Theoretical Approach to the Investigation of Nafcillin Sodium Solubility

A comprehensive understanding of the thermodynamic properties of substances is an essential foundation for the successful development, optimization, and scale-up of crystallization processes. To address the lack of data on the solubility and thermodynamic properties of nafcillin sodium, the solubility data of nafcillin sodium in six pure solvents, namely, methanol, ethanol, acetonitrile, acetone, isopropanol, and butyl acetate, as well as two binary solvents of methanol–acetone and methanol–butyl acetate, were determined by using the dynamic gravimetric method. It was found that the solubility of nafcillin sodium was greatly affected by the temperature and solvent type, with greater solubility in alcohol solvents and poorer solubility in ester solvents. In addition, the solubility of nafcillin sodium in a binary solvent system increased with the increase of the molar ratio of methanol. Meanwhile, the experimental solubility data were correlated by applying the Apelblat model, λh model, and nonrandom two-liquid (NRTL) model, among which the Apelblat model provided the best fit. In addition, the microscopic reasons for the significant differences in the solubility properties between different pure solvents were also revealed by molecular simulations. The solute–solvent interactions were analyzed using radial distribution function (RDF), mean square displacement (MSD), and solvation free energy (SFE). It was found that the strongest interaction was between nafcillin sodium and methanol, and the solute had the highest diffusion coefficient in methanol with good solubility.