In this study, the solubility of (R, S)-(±)-sodium ibuprofen dihydrate solids at 25 °C was determined in 23 solvents using a robust and scalable initial solvent-screening method (13). Good solvents were identified, and the solubility curves of the solids in various good solvents were constructed. Good solvents were defined as solvents in which the solubility of racemic (R, S)-(±)-sodium ibuprofen dihydrate had a solubility of < 1 mg/mL at 25 °C. All solids were produced from the supersaturated solution of the good solvents by temperature cooling from 60–25 °C.
Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD) determined the polymorphism, crystallinity, and drying scheme of the solid samples (14). Optical microscopy (OM) and scanning electron microscopy (SEM) were used for crystal-habit imaging. The solids' solubilities and crystal habits were related to the solvent microscopic properties of dispersion forces (δd) polar forces (δp), and hydrogen bonding (δh) by the Hansen model adopted from the paint industry at 25 °C (15).Solvent liquids generally are held together by van der Waals forces, which are electromagnetic interactions among molecules. The strength of van der Waals forces is directly reflected by the heat of vaporization (ΔHv). ΔHv can be translated into a correlation between vaporization and the solubility behavior because the types of intermolecular attractive forces needed to be overcome to vaporize a solvent liquid are the same as those that must be overcome to dissolve it. The Hildebrand numerical value (δt[Pa1/2 ]) of the solvency behavior of a specific solvent was invented as a function of ΔHv (15) in the following:
in which R is the gas constant (8.314 J/mol • K), T is the temperature (measured in K), and Vm is the molar volume (measured in m3 /mol).