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

• Published in: Crystal growth & design Vol. 12; no. 12; pp. 6118 - 6125
• Main Authors: Chernyshev, Vladimir V, Yatsenko, Alexandr V, Pirogov, Sergey V, Nikulenkova, Tamara F, Tumanova, Ekaterina V, Lonin, Ivan S, Paseshnichenko, Ksenia A, Mironov, Andrei V, Velikodny, Yurii A
• Format: Journal Article
• Language: English
• Published: Washington,DC American Chemical Society 05-12-2012
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg3012475

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  III and IV  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 2–3 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 ↔ IIIh depending on the relative humidity is proposed.