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Title: An exploration of polymorphism in pharmaceutical compounds using high pressure
Author: Abbas, Nasir
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2010
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The effects of high pressure on a selection of organic compounds have been studied. Crystallisation at high pressure has been successfully used to grow a single crystal of an elusive polymorph (form II) of mefenamic acid. Milling experiments revealed that form I can be converted to form II by milling at both ambient temperature and at -78 °C. Direct compression of powder samples of form I at 1.5 GPa using methanol:ethanol as a pressure-transmitting medium resulted in the formation of a new high-pressure form III and this new form is recoverable to ambient pressure. Compression of powder samples of forms I and II using Fluorinert- FC77 as a pressure-transmitting medium resulted in a reversible phase transition to a new high-pressure form IV. High-pressure crystallisation of N,N'-dimethylurea resulted in the formation of two new high-pressure polymorphs designated as forms III and IV. Crystal structures of these forms are reported here. Form III was also produced by compression of a powder samples of form I and decompression studies showed that it can be recovered to ambient pressure, but it was metastable compared to form I. Form II was produced through compression of form I using Fluorinert FC-77 as a pressure-transmitting medium. Form IV was produced by heating a mixture of form II and III to 150 °C at 1.75 GPa. Decompression of form IV resulted in formation of a new form, which was recoverable at ambient pressure. The experimental results have been compared with crystal structure prediction calculations. High-pressure techniques have been used to study polymorphism of GSK developmental compounds A and B. New polymorphs for these compounds have been obtained at high pressure. Of particular importance are forms III and VI of compounds A and B, respectively, where recrystallisation at high pressure resulted in production of these forms and decompression studies have shown that they can be recovered to ambient pressure. From the compression studies performed on the powder samples of compound A, two new high-pressure forms designated as forms V and VI were obtained at 0.9 and 1.4 GPa, respectively. New polymorphs for these compounds were also produced from recrystallisation at ambient pressure.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available