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

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.