A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs

The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development of the favored monohydrate form. Inspired by crystal structure prediction, the search for neat polymorphs was expanded to an unusual range of experiments, including melt crystallization under pressure, to work around solvate formation and the thermal instability of the molecule. Ten polymorphs of galunisertib were found; however, the structure predicted to be the most stable has yet to be obtained. We present the crystal structures of all ten unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modeling techniques to produce a complete structure landscape and assess the risk of late-appearing, more stable polymorphs. The exceptional conformational polymorphism of this prolific solvate former invites further development of methods, computational and experimental, that are applicable to larger, flexible molecules with complex solid form landscapes

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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High-pressure structural studies of energetic materials

This article reviews how the advances in the techniques for the collection and analysis of high-pressure X-ray and neutron diffraction data, augmented by spectroscopic data, now permit the accurate determination of the full crystal structure of energetic materials under extreme conditions. Using these methods, the crystal structure of the high-pressure gamma-form of RDX (1,3,5-trinitrohexahydro-striazine) has been determined - the first case of a high-pressure structure of an energetic material. In addition, the crystal structure of the highly metastable beta-form has been determined and, contrary to the previous reports, has been shown to be different from the form obtained at elevated temperatures and pressures