Structural and Thermodynamic Features of Three Stable Crystal Forms of Temazepam: A Sedative Drug

Two anhydrous crystal forms (Form X and Form VI) of temazepam were determined by single crystal X-ray diffraction and compared with the crystal structure of the literature crystal form, Form 0. All three polymorphic forms have Z′ > 1. Forms 0 and VI reveal a self-inclusion host–guest type crystal packing whereas Form X shows a layered 3D-packing arrangement. The three polymorphic forms are monotropically related, and their relative thermodynamic stability is in the following order: Form 0 > Form X > Form VI. This study further reveals the origin of the thermodynamically more stable form (Form 0) and evaluates its intriguing structural and thermodynamic features with two other stable crystal forms: Forms X and VI, respectively.