Zileuton (ZIL) is an active oral inhibitor of the enzyme 5-lipoxygenase used for the maintenance treatment of asthma. Though ZIL was first approved by the United States FDA 20 years ago, structural knowledge of this active pharmaceutical ingredient (API) has been omitted. Here, we report the crystal structure of the commercially available anhydrous ZIL (form A) for the first time. It's also found that a monohydrate of ZIL (form H) can be formed when the compound is exposed to high relative humidity (RH) conditions. Such a phase change is not desired during manufacturing and storage, for the physicochemical and pharmacokinetic behaviours of ZIL may also be modified along with the solid state hydration. Cocrystallization experiments involving ZIL with nicotinamide (NIC) and isonicotinamide (ISO) were successfully performed and the obtained cocrystal forms, ZIL–NIC and ZIL–ISO, demonstrated superior phase stability against moisture. Additionally, all these ZIL forms were characterized by a variety of analytical methods, which provide plentiful information for the solid-state landscape of this important drug substance.

中文翻译：

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齐留通的共晶体具有增强的物理稳定性†

Zileuton（ZIL）是5-脂氧合酶的活性口服抑制剂，可用于哮喘的维持治疗。尽管ZIL于20年前首次获得美国FDA批准，但该活性药物成分（API）的结构知识已被省略。在这里，我们首次报告了可商购的无水ZIL（A型）的晶体结构。还发现当该化合物暴露于高相对湿度（RH）条件下时，可以形成ZIL（H型）的一水合物。这种相变在制造和存储期间是不期望的，因为ZIL的物理化学和药代动力学行为也可以随着固态水合而改变。ZIL与烟酰胺（NIC）和异烟酰胺（ISO）的共结晶实验成功进行，获得的共晶形式ZIL–NIC和ZIL–ISO表现出优异的防潮相稳定性。此外，所有这些ZIL形式均通过多种分析方法进行了表征，这些分析方法为该重要原料药的固态图谱提供了丰富的信息。