Combined Experimental\nand Theoretical Approach to\nthe Investigation of Nafcillin Sodium Solubility

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