Eltrombopag, of C25H22N4O4 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.
Keywords: Eltrombopag; X-ray diffraction; pattern indexing; polymorphism; thermal analysis.