TY  - JOUR
PB  - American Chemical Society
IS  - 5
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10071313
Y1  - 2019/05/01/
A1  - Askin, S
A1  - Cockcroft, J
A1  - Price, L
A1  - Goncalves, A
A1  - Zhao, M
A1  - Tocher, D
A1  - Williams, G
A1  - Gaisford, S
A1  - Craig, D
SN  - 1528-7483
N2  - 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.
AV  - public
VL  - 19
TI  - Olanzapine form IV: discovery of a new polymorphic form enabled by computed crystal energy landscapes
EP  - 2757
SP  - 2751
JF  - Crystal Growth and Design
UR  - https://doi.org/10.1021/acs.cgd.8b01881
ER  -