Hexamorphism of Dantrolene: Insight into the Crystal Structures, Stability, and Phase Transformations

Dantrolene represents yet another interesting example of abundant molecular crystal polymorphism existing in at least six different neat polymorphs, three of which can be obtained via crystallization (I-III) and an additional three (IV- VI) via solid-state dehydration from three different monohydrates (MH-I-MH-III). The reasons for polymorph formation were rationalized by analyzing the crystal structures of the polymorphs and hydrates used in their preparation. The thermodynamic relations among the polymorphs were established from calorimetric data, solubility measurements, and lattice energy calculations