Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt-Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study
Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt-Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study
复制标题
DOI：
10.1021/acs.cgd.6b00771
复制
发表时间：
2016-09-01
影响因子：
3.8
通讯作者：
Yonemochi, Etsuo
中科院分区：
文献类型：
--
作者：
Putra, Okky Dwichandra;Yoshida, Tomomi;Yonemochi, Etsuo
Dimenhydrinate (DIM) is an important drug used for the prevention of motion sickness. Surprisingly, the crystal structure of DIM has not been determined over the last 67 years. In this study, we have attempted to determine the structure of DIM through single crystal X-ray structure analysis and confirmed the salt-cocrystal ambiguity. Because of the existence of proton transfer, DIM exists as a salt crystal. The crystal structure of DIM contains the anionic form of 8-chlorotheophylline whose existence was confirmed using density functional theory calculation. Other solid-state characterizations based on spectroscopy and thermal analysis were also conducted in order to fill the vacancy regarding the solid-state characterization. Kinetic and intrinsic solubility tests were also performed to evaluate the physicochemical properties of DIM raw material.
