Preparation and Solid-State Characterization of Eltrombopag Crystal Phases

Abstract

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.

Entropy analysis and grey correlation coefficient cluster analysis of multiple indexes of 5 kinds of condiments

“…The results of thermo gravimetric analysis 1) Thermo gravimetric analysis of cinnamon (Abbinante et al, 2020;Aqel et al, 2021;Assali et al, 2020;Bashiri et al, 2021) The thermo gravimetric data of cinnamon are shown in Figure 2, Figure 3 and Table 2. It can be seen from 3) Thermogravimetric analysis of clove…”

Repurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus

“…Eltrombopag (EP), a non-peptide small molecule agonist of the human thrombopoietin receptor (TpoR), was discovered by screening small molecular libraries to bind TpoR and stimulate its downstream signaling, and further rationally designed to improve yielding and purity ( Bussel et al, 2019 ). The bisolamine salt EP Olamine [EP(O)] is the most common formulation, which was found to be easily produced, orally ingestible and environmentally stable ( Abbinante et al, 2020 ). EP is mainly used in the oral treatment of idiopathic thrombocytopenic purpura (ITP) ( Erickson-Miller et al, 2009 ).…”

Thermal and Structural Characterization of Two Crystalline Polymorphs of Tafamidis Free Acid

“…Conventional experimental methods employed to assess, at constant pressure, the relative thermal stability of polymorphs are thermoanalytical (DSC/TGA) or variable-temperature X-ray powder diffraction (VTXRD) analyses. Coupling these two techniques with structural powder diffraction analysis, which can provide atomic-scale models of polymorphs that cannot be isolated as single crystals of suitable size and quality, is now possible, and has largely benefited from the pioneering work of a few academic research groups [ 13 ], including ours [ 14 ].…”