Donepezil Multicomponent Systems: Donepezil–Water–Maleic Acid Crystals and More

• Published in: Crystal growth & design Vol. 20; no. 4; pp. 2283 - 2293
• Main Authors: Bae, Jae Ho, Sun, Hyun Ji, Park, Arm, Kim, Daeyoung, Yeon, Jisun, Kang, Sung Kwon, Lee, Eun Hee
• Format: Journal Article
• Language: English
• Published: American Chemical Society 01.04.2020
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.9b01413

Eight donepezil multicomponent systemssix new multicomponent systems (donepezil–mandelic acid, donepezil–mandelic acid–water, donepezil–water–maleic acid, donepezil–fumaric acid, donepezil–benzenesulfonic acid–water, and donepezil 3.5 hydrate) and two known multicomponent systems (donepezil–benzenesulfonic acid and donepezil–oxalic acid–water)were investigated in the present study. A detailed structural and spectroscopic analysis of the donepezil multicomponent systems was conducted to determine which interactions are involved and which class each system belongs to. It was found that various interactions, such as cation–anion, water–cation, water–anion, hydrogen-bond, and water–water interactions, were present in these systems. In addition, an interesting donepezil–maleic acid multicomponent system that only exists in an amorphous form in the absence of water was discovered. Water is necessary to bridge the donepezil molecules with the maleic acid molecules in the crystalline state; therefore, no acid–base interaction is observed in the system. This type of interaction is difficult to identify without single-crystal X-ray analysis. This donepezil–maleic acid multicomponent system is neither a salt nor a cocrystal system, even though the system includes basic drug and acid components, but may represent a donepezil multicomponent hydrate. This study illustrates the importance of detailed analysis to determine the interactions present within multicomponent systems and demonstrates the interesting multicomponent hydrate system.