Solubilities and Transformations of Anhydrous and Hydrated Forms of N-Acetyl-D-Neuraminic Acid in Water–2-Propanol Solutions

Abstract

2-Propanol is used in the industrial crystallization of N-acetyl-D-neuraminic acid (NANA) to reduce its solubility, thereby enhancing its recovery. This study investigates the solubility and transition of NANA in mixed water–2-propanol systems. The solubility of NANA was measured within the temperature range of 273–336 K using high-performance liquid chromatography (HPLC) to determine the equilibrium compositions of NANA in aqueous solutions containing 67.9, 57.2, 35.5, 19.0, 9.2, 2.6 and 0 mol% of 2-propanol. Powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were employed to investigate the crystalline states of NANA. Thermodynamic properties, such as the entropy and enthalpy of dissolution, were estimated by applying the Van’t Hoff equation to plotting the solubility data. The mechanism of transformation from the anhydrous to dihydrated form is interpreted by considering the change in the water activity (primarily determined by the percentage of water and 2-propanol) of the solution. The results demonstrate that the states of NANA dihydrate and anhydrous NANA in water–2-propanol mixtures depend on both the water activity and temperature. These conclusions can provide useful information for determining the crystallization parameters needed to obtain a desired anhydrous or hydrated phase.