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Instruments / Technical Area	Publication Details	Published	Actions
I19-Small Molecule Single Crystal Diffraction	A prolific solvate former, galunisertib, under the pressure of crystal structure prediction, produces ten diverse polymorphs Rajni M. Bhardwaj , Jennifer A. Mcmahon , Jonas Nyman , Louise S. Price , Sumit Konar , Iain D. H. Oswald , Colin R. Pulham , Sarah L. Price , Susan M. Reutzel-Edens Journal Of The American Chemical Society DOI: 10.1021/jacs.9b06634 Diamond Proposal Number(s): [16139] Open Access Show Abstract ▼ Abstract: 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 10 unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modelling 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.	Aug 2019
I12-JEEP: Joint Engineering, Environmental and Processing	Olanzapine form IV: discovery of a new polymorphic form enabled by computed crystal energy landscapes Sean Askin , Jeremy K. Cockcroft , Louise S. Price , Andrea Goncalves , Min Zhao , Derek A. Tocher , Gareth R. Williams , Simon Gaisford , Duncan Q. M. Craig Crystal Growth & Design DOI: 10.1021/acs.cgd.8b01881 Diamond Proposal Number(s): [17450] Show Abstract ▼ Abstract: Olanzapine is a polymorphic drug molecule that has been extensively studied, with over 60 structures reported in the Cambridge Structural Database. All anhydrous and solvated forms of olanzapine known to date contain the SC0 dimer packing motif. In this study, a new screening approach was adopted involving heat-induced forced crystallization from a polymer-based molecular dispersion of olanzapine. Simultaneous differential scanning calorimetry-powder X-ray diffraction (DSC-PXRD) was used to heat the amorphous dispersion and to identify a novel physical form from diffraction and heat flow data. Comparison of the diffraction data with those from a computed crystal energy landscape allowed the crystal structure to be determined. The result was the discovery of a new polymorph, form IV, which does not use the SC0 motif. Hence, while dimer formation is the dominant process that defines crystal packing for olanzapine formed from solution, it seems that molecularly dispersing the drug in a polymeric ma-trix permits crystallization of alternative motifs. Having identified form IV, it proved possible to scale up the synthesis and demonstrate its enhanced dissolution properties over form I.	Mar 2019

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