Crystallographic tomography and molecular modelling of structured organic polycrystalline powders

March 02, 2021

Parmesh Gajjar (1), Thai T. H. Nguyen (2), Jun Sun (3), Ioanna D. Styliari (4), Hrishikesh Bale (5), Samuel A. McDonald (1), Timothy L. Burnett (1), Benjamin Tordoff (6), Erik Lauridsen (3), Robert B. Hammond (2), Darragh Murnane (4), Philip J. Withers (1,7), Kevin J. Roberts (2)

CrystEngComm, 23, 2021:2520-2531. DOI: 10.1039/D0CE01712D


A fundamental understanding of the behaviour of polycrystalline materials, including pharmaceuticals, is vital for control of their physicochemical and crystalline properties, which in turn has the potential to improve drug product development for example. In this work, attenuation X-ray computed tomography (CT) and diffraction contrast tomography (DCT) are combined with molecular modelling to understand the powder packing behaviour and crystal interactions of the organic cubic compound hexamine (hexamethylenetetramine). It is the first application of DCT to polycrystalline organic materials. The crystal morphology is predicted through synthonic modelling, with fully 3D-resolved confirmation of the crystallography of the external {110} facets, edges and corner directions by DCT. Analysis of the powder-bed reveals agglomerate structures and orientational texture, with its chemical origins energetically predicted to be face-to-face in accordance with the experimental data. Finally, measurements of crystal & crystallite interactions provide evidence for different mechanisms of powder bed agglomeration.

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Author Affiliation

(1) Henry Moseley X-ray Imaging Facility, Department of Materials, The University of Manchester, Manchester, M13 9PL, UK
(2) Centre for the Digital Design of Drug Products, School of Chemical and Process Engineering, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
(3) Xnovo Technology ApS, Theilgaards Alle 9,1th, 4600 Køge, Denmark
(4) School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK
(5) Carl Zeiss X-ray Microscopy, 4385 Hopyard Rd #100, Pleasanton, CA 94588, USA
(6) Carl Zeiss Microscopy GmbH, Carl-Zeiss-Straße 22, 73447 Oberkochen, Germany
(7) Henry Royce Institute for Advanced Materials, The University of Manchester, Manchester, M13 9PL, UK