Crystal Structures, Stability, and Solubility Evaluation of Two Polymorphs of a 2:1 Melatonin–Piperazine Cocrystal

• Published in: Crystal growth & design Vol. 20; no. 2; pp. 1079 - 1087
• Main Authors: Yan, Yan, Dai, Xia-Lin, Jia, Jun-Long, Zhao, Xing-Hua, Li, Zhi-Wei, Lu, Tong-Bu, Chen, Jia-Mei
• Format: Journal Article
• Language: English
• Published: American Chemical Society 05.02.2020
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.9b01405

The polymorphism of cocrystals is not studied as widely as that of single-component crystals. In this work, two polymorphic forms of a cocrystal of melatonin with piperazine (MLT–PIP I and MLT–PIP II) in a 2:1 stoichiometry were successfully obtained and fully characterized. The crystal structures exhibit differences in hydrogen bonding modes and molecular packing arrangements across two polymorphs. Theoretical computations were carried out to compare their crystal lattice energy. They were also evaluated by thermal analysis, variable temperature X-ray powder diffraction, and dynamic vapor sorption measurements, as well as powder and intrinsic dissolution experiments. The results of experimental and theoretical studies conclude that MLT–PIP II, as the stable form, exhibits a significantly improved solubility and dissolution rate and is suitable to be developed into a more efficient formulation of melatonin.