Aniracetam Solubility in Pure and Binary Solvents: Effect of Molecular Interaction and Analysis of Crystallized Products

The aim of this work is to study the solubility of aniracetam and discuss the molecular interaction between solute and solvent in the dissolution process. This work would be important to optimize the crystallization and extraction process of aniracetam. The equilibrium data of aniracetam in seven pure solvents including methanol, ethanol, n-propanol, isopropyl alcohol, acetone, toluene, ethyl acetate, and three binary mixtures were measured by using the isothermal saturation method from T = 273.15 to 318.15 K. The solubility of aniracetam in pure and mixed solvents increased with the increasing temperature. At a given temperature, the solubility of aniracetam in (acetone + alcohols) increased with increasing mass fraction of acetone. Moreover, it was greater in (acetone + methanol) than other mixed systems. The maximum solubility of aniracetam in pure solvents was obtained in acetone, and the order they follow from small to large is (n-propanol < isopropyl alcohol < ethanol < methanol < toluene < ethyl acetate < acetone). Two pure solvent models (modified Apelblat equation, λh equation) and two cosolvent models (CNIBS/R-K model and Jouyban–Acree model) were applied to analyze the obtained solubility data. The correlation showed the experiment data is very close to the calculated values and exhibit low values of RAD and RMSD. Infrared spectra recorded between crystallized products and raw material in the pure dry KBr matrix in pairs and Pearson correlation coefficient were used to quantify the degree of similarity. Furthermore, powder X-ray diffraction (PXRD) was applied before and after the experiments to analyze the crystal form of aniracetam studied in this work.