Understanding solvent effects on solvatomorphisms of donepezil-maleic acid

The aim of this work is to investigate the action of solvents in the preparation of donepezil-maleic acid. Five forms of donepezil-maleic acid, including: anhydrous donepezil-maleic acid (DM), donepezil-maleic acid-acetone (DM-A), donepezil-maleic acid-ethyl acetate (DM-EA), donepezil−maleic acid-ethanol (DM-E) and donepezil-maleic acid-water (DM-W), were prepared by mechanochemistry. The crystal structures of the four solvates were determined by single crystal X-ray diffraction, and structure analysis showed that solvents without OH hydrogen bond donors (acetone and ethyl acetate) were weakly connected with donepezil-maleic acid only by atypical hydrogen bonds in the lattice, while solvents containing hydrogen bond donors (ethanol and water) provided strong intermolecular interactions to maintain the spatial structure. Furthermore, the desolvation process and stability of five forms were investigated by various analytical techniques including powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. In addition, the crystal transformation relationship of the mentioned forms was explored. The result showed that DM-W was the most stable form among the five forms, which was attributed to the strong hydrogen bonding network.