In drug development, evaluating the stability of the hydrate is particularly important because changes in the hydration state could cause alterations of the physicochem. properties. In this study, it was found that ondansetron hydrochloride dihydrate, a competitive serotonin type 3 receptor antagonist, dehydrated to anhydrate in two steps with a hemihydrate form as an intermediate. The crystal structures of the unstable hemihydrate and anhydrate forms were successfully analyzed through the structure detn. from powder diffraction data technique using high-temp. synchrotron X-ray diffraction data. Comparison of the crystal structures of the dihydrate and hemihydrate revealed that in the first dehydration step the water mol. hydrogen-bonded to the imidazole ring was removed. In the second step, the remaining water mol. that was closely bound to the chloride anions was removed to form a void. Moreover, the mol. rearrangement caused by the dehydration was examd. through anal. of the intermol. interactions. Furthermore, the hygroscopic properties of the hydration and dehydration were investigated. These phase transitions triggered by dry and high temp. conditions are common in drug development. Therefore, the crystal structure and physicochem. properties of all phases of hydrates and anhydrates should be characterized. [on SciFinder(R)]
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