Various solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical industry. By recrystallization from ethyl acetate, a novel polymorph of 6-fluoro-3-hydroxypyrazine-2-carboxamide (trademark favipiravir, RNA polymerase inhibitor) was obtained and characterized using differential scanning calorimetry (DSC), infra-red spectroscopy and powder X-ray diffraction (XRD) analysis. The favipiravir molecule in two polymorphs realizes similar H-bonding motifs, but the overall H-bonded networks differ. Based on periodic density functional theory calculations, the novel tetragonal polymorph with two interpenetrated H-bonded networks is slightly less stable than the orthorhombic one with the zst topology of the underlying H-bonded net that is in accord with experimentally observed powder XRD patterns of slow conversion of the tetragonal phase to the orthorhombic one. However, topological analysis of net relations revealed that no transformations can be applied to convert H-bonded networks in the experimental unit cells, and DSC data indicate no solid-state reactions at heating.

中文翻译：

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法维拉韦的新型多晶型物–抗病毒药

药学上重要的化合物的各种固体形式表现出不同的物理性质和生物活性。因此，了解活性药物成分的结构概况和自发多晶型转变的预测对制药业具有实用价值。通过从乙酸乙酯中重结晶，获得了新型的6-氟-3-羟基吡嗪-2-羧酰胺多晶型物（商标为favipiravir，RNA聚合酶抑制剂），并使用差示扫描量热法（DSC），红外光谱和粉末X射线分析对其进行了表征。衍射（XRD）分析。两个多晶型物中的favipiravir分子可实现相似的H键基序，但整体H键网络不同。根据周期密度泛函理论计算，底层H键网的zst拓扑结构，与实验观察到的粉末状XRD模式相一致，该模式将四方相缓慢转化为正交晶体。但是，对净关系的拓扑分析显示，在实验单位晶胞中无法应用任何转换来转换H键网络，并且DSC数据表明在加热时没有固态反应。