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.

中文翻译：

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2：1褪黑素-哌嗪共晶体的两个多晶型的晶体结构，稳定性和溶解性评估

共晶的多态性没有像单组分晶体那样被广泛研究。在这项工作中，成功获得了褪黑激素与哌嗪共结晶的两种多晶型物（MLT-PIP I和MLT-PIP II），其化学计量比为2：1。晶体结构在两个多晶型物之间的氢键合模式和分子堆积安排上表现出差异。进行了理论计算以比较它们的晶格能量。还通过热分析，可变温度X射线粉末衍射和动态蒸气吸附测量以及粉末和固有溶解实验对它们进行了评估。实验和理论研究的结果表明，MLT–PIP II，作为稳定的形式，表现出显着改善的溶解度和溶解速率，并且适合发展为褪黑激素的更有效制剂。