Solid-State Forms of Koumine Hydrochloride: Phase Transformations and the Crystal Structure and Properties of the Stable Form

[Image: see text] To investigate the solid-state forms of koumine hydrochloride (KMY), solid form screening was performed, and one amorphous form and five crystalline forms (forms A, B, C, D, and E) were identified by powder X-ray diffraction. Form A was the dominant crystal product, and its crystal structure and packing pattern were determined by single-crystal X-ray diffraction. The crystals displayed an orthorhombic crystal system and symmetry of space group P2(1)2(1)2(1) with Z′ = 1. The amorphous form transformed to form A at 105–120 °C or 75% RH, while forms B, C, D, and E could only be intermediate phases and readily transformed to form A at room temperature. Therefore, the phase transformations of KMY solid-state forms were established. The properties of the amorphous form and form A were further elucidated by applying vibrational spectroscopy, moisture sorption analysis, and thermal analysis. Accordingly, form A, the KMY anhydrate, was found to be the thermodynamically stable form with low hygroscopicity under ambient conditions. These characteristics are crucial in the manufacture and storage of active pharmaceutical ingredients.