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Determination of the Crystal Structure of a New Polymorph of Theophylline
Author(s) -
Eddleston Mark D.,
Hejczyk Katarzyna E.,
Bithell Erica G.,
Day Graeme M.,
Jones William
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201204369
Subject(s) - crystallite , crystal structure , transmission electron microscopy , crystal structure prediction , theophylline , crystallography , materials science , electron diffraction , diffraction , crystal (programming language) , chemistry , analytical chemistry (journal) , nanotechnology , optics , chromatography , physics , computer science , medicine , programming language , endocrinology
A new approach to crystal structure determination, combining crystal structure prediction and transmission electron microscopy, was used to identify a potential new crystal phase of the pharmaceutical compound theophylline. The crystal structure was determined despite the new polymorph occurring as a minor component in a mixture with Form II of theophylline, at a concentration below the limits of detection of analytical methods routinely used for pharmaceutical characterisation. Detection and characterisation of crystallites of this new form were achieved with transmission electron microscopy, exploiting the combination of high magnification imaging and electron diffraction measurements. A plausible crystal structure was identified by indexing experimental electron‐diffraction patterns from a single crystallite of the new polymorph against a reference set of putative crystal structures of theophylline generated by global lattice energy minimisation calculations.