Dipartimento di Scienza e Alta Tecnologia & To.Sca.Lab., Università dell'Insubria, via Valleggio 11, 22100 Como, Italy.
Chemessentia srl, via Bovio 6, 28100 Novara, Italy.
Molecules. 2020 Dec 25;26(1):65. doi: 10.3390/molecules26010065.
Eltrombopag, of CHNO chemical formula, is a drug used against thrombocytopenia, marketed worldwide under different tradenames in the form of its bis-olamine salt. The free acid (CAS no. 496775-61-2) is an intermediate species used for the final drug isolation and is reported to crystallize in more than 20 distinct crystal forms, including a large number of hydrates and solvates. Their identification, and, ultimately, their quantification in industrial lots require the usage of accurately measured X-ray powder diffraction pattern, as well as the assessment of the metrical features (crystal symmetry and lattice parameters), nowadays accessible by powerful crystallographic software. Here, the complete indexing of 13 monophasic samples, prepared using literature or newly tailored crystallization methods, jointly to simultaneous thermogravimetric and calorimetric analyses and to variable temperature X-ray diffraction studies, provide a clear picture of the stability fields of the different crystal phases and their mutual interconversion processes, leading, in a few cases, to new and unexpected crystalline polymorphs or solvates of the pristine unsolvated Form I.
依替膦酸二钠，化学式为 CHNO，是一种用于治疗血小板减少症的药物，以其双羟胺盐的形式在全球范围内以不同的商品名销售。游离酸（CAS 号 496775-61-2）是用于最终药物分离的中间物种，据报道可结晶成 20 多种不同的晶体形式，包括大量的水合物和溶剂化物。为了对工业批次中的这些化合物进行鉴定和最终定量分析，需要使用准确测量的 X 射线粉末衍射图谱，并评估其度量特征（晶体对称性和晶格参数），这些都可以通过强大的晶体学软件来实现。在这里，通过同时进行热重分析和量热分析以及变温 X 射线衍射研究，对使用文献或新定制的结晶方法制备的 13 种单相样品进行了完全索引，这清楚地展示了不同晶体相的稳定场及其相互转化过程，在某些情况下，导致了原始非溶剂化的 I 型的新的和意想不到的晶态多晶型物或溶剂化物。
