Thesis

Structural insights into pharmaceutical solids from synchrotron and laboratory x-ray powder diffraction data

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Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13212
Qualification Level
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Department, School or Faculty
Abstract
  • Structural insights into a wide range of pharmaceutically relevant solids, including pharmaceutical salts, co-crystals and amorphous solids have been gained through the use of X-ray powder diffraction techniques. By combining global optimisation methods with high-quality powder diffraction data collected in the laboratory or at a synchrotron radiation source, the crystal structures of pharmaceutically relevant materials were solved successfully and reproducibly. The crystal structures which were solved are moderately complex, and at the midpoint of the complexity that can be routinely tackled by the DASH structure solution package. The crystal structures of six salts of the β2-adrenoceptor agonist, salbutamol were solved directly from powder diffraction data collected in the laboratory. For five of these salts, no single crystals could be grown, however, for one salt, a single crystal was obtained, and comparison of the single crystal structure with the structure solved from powder diffraction data confirms the excellent accuracy of structures from powder diffraction data. Co-crystals of the anti-epileptic drug, carbamazepine were examined on beamline I11 at Diamond Light Source in Oxfordshire. The beamline was in the optimisation phase when the co-crystals were examined, and were the first fully organic structures to be examined on the beamline. The accuracy of the structures solved from powder data was confirmed by comparison with published single crystal structures. Additional carbamazepine co-crystal structures were solved from laboratory powder diffraction data in order to assess the increase in accuracy associated with high resolution powder diffraction collected at a synchrotron radiation source. Total scattering pair distribution function (TS-PDF) analysis was carried out on nanocrystalline powders of carbamazepine and the NSAID indomethacin, and it was found that melt-quenched "amorphous" carbamazepine is in actual fact a nanocrystalline version of form II, which is the clinically used polymorph.
Advisor / supervisor
  • Florence, Alastair J.
  • Shankland, Kenneth
Resource Type
DOI
Date Created
  • 2012
Former identifier
  • 947980

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