Hydrates are common in pharmaceutical development, and the formation of hydrates affects the performance of the final product. However, the role that water plays in crystal packing remains unclear. In this study, Avibactam sodium, which has one dihydrate (Form E), one monohydrate (Form A), and two anhydrous forms (Form B and D), was chosen as the model compound to understand this subject. Single crystal structures of four solid forms were obtained and characterized by single X-ray diffraction. The dynamic vapor sorption experiments revealed the moisture-dependent stability increased in the order: Form B < Form D < Form A < Form E. It can be envisaged that the integration of water molecules could noticeably compensate the potential intermolecular interactions, thereby significantly improving the crystal stabilities of hydrates. Furthermore, the hydration of Form B was investigated to understand the integration of water molecules by measuring the critical hydration water activities (a_w). The results indicated that both water activities and temperature are vital factors to determine the amount of water molecules existing in crystal lattice. Moreover, to probe the disintegration of water molecules, the dehydration of dihydrate was investigated in detail by solid-state transformation and solvent-mediated transformation experiments. Finally, two-step dehydration and one-step dehydration + recrystallization mechanisms of these different pathways were proposed by analyzing the transformation experiment results and the crystal structure of various solid forms.

中文翻译：

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了解水在阿维巴坦钠不同固体形式中的作用及其影响机理

水合物在药物开发中很常见，水合物的形成会影响最终产品的性能。但是，水在晶体堆积中所起的作用仍不清楚。在这项研究中，选择具有一种二水合物（形式E），一种一水合物（形式A）和两种无水形式（形式B和D）的阿维巴坦钠作为模型化合物，以了解该主题。获得四种固体形式的单晶结构，并通过单X射线衍射表征。动态蒸气吸附实验表明，与水有关的稳定性按以下顺序增加：B型<D型<A型<E型水合物的晶体稳定性。此外，一个_{w ^}）。结果表明，水分活度和温度都是决定晶格中水分子含量的重要因素。此外，为了探测水分子的分解，通过固态转化和溶剂介导的转化实验详细研究了二水合物的脱水。最后，通过分析转化实验结果和各种固体形式的晶体结构，提出了这些不同途径的两步脱水和一步脱水+再结晶机理。