Two Anhydrous and a Trihydrate Form of Tilorone Dihydrochloride: Hydrogen-Bonding Patterns and Reversible Hydration/Dehydration Solid-State Transformation

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• 作者：Vladimir V. Chernyshev ; Alexandr V. Yatsenko ; Sergey V. Pirogov ; Tamara F. Nikulenkova ; Ekaterina V. Tumanova ; Ivan S. Lonin ; Ksenia A. Paseshnichenko ; Andrei V. Mironov ; Yurii A. Velikodny
• 刊名：Crystal Growth & Design
• 出版年：2012
• 出版时间：December 5, 2012
• 年：2012
• 卷：12
• 期：12
• 页码：6118-6125
• 全文大小：684K
• 年卷期：v.12,no.12(December 5, 2012)
• ISSN：1528-7505

文摘

During the polymorph screening of an active pharmaceutical ingredient tilorone dihydrochloride (chemical name 2,7-bis[2-(diethylamino)ethoxy]-9-fluorenone dihydrochloride) two new polymorphic modifications 鈥?III and IV 鈥?were obtained. The crystal structures of both polymorphs were established from X-ray powder diffraction. An interesting phenomenon has been observed at ambient conditions for III, which transforms into a novel hydrated form IIIh during 2鈥? h when the humidity in the storage room increases to 70% or more. As soon as the relative humidity falls to 30% or less, IIIh transforms into the parent anhydrous form III within an hour. Form IIIh has been identified as a trihydrate of tilorone dihydrochloride, and its crystal structure has been established from X-ray powder diffraction. On the basis of the crystal structures and hydrogen-bonding patterns, a mechanistic model of reversible hydration/dehydration solid-state transformation III 鈫?IIIh depending on the relative humidity is proposed.