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Olanzapine form IV: discovery of a new polymorphic form enabled by computed crystal energy landscapes

Askin, S; Cockcroft, J; Price, L; Goncalves, A; Zhao, M; Tocher, D; Williams, G; ... Craig, D; + view all (2019) Olanzapine form IV: discovery of a new polymorphic form enabled by computed crystal energy landscapes. Crystal Growth and Design , 19 (5) pp. 2751-2757. 10.1021/acs.cgd.8b01881. Green open access

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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 demon-strate its enhanced dissolution properties over form I.

Type: Article
Title: Olanzapine form IV: discovery of a new polymorphic form enabled by computed crystal energy landscapes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.cgd.8b01881
Publisher version: https://doi.org/10.1021/acs.cgd.8b01881
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10071313
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