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Title: Pharmaceutical polymorphs : crystallisation, stabilisation and delivery
Author: Capes, J. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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The work presented here describes a novel method for crystallising the metastable polymorph of paracetamol from an evaporating aqueous solution. Generally this form cannot be obtained from solution as it undergoes a rapid solvent-mediated phase transformation to the more stable form. In this new method it is found that the metastable polymorph nucleates and grows at the edge of the meniscus. The crystals form here due to favourable surface tension forces and a localised concentration increase. The metastable crystal is then unable to transform to the more stable form because the crystals are effectively removed from the solvent as the level of the solution drops away from this region as evaporation proceeds. The ability to obtain metastable polymorphs is particularly interesting as they can offer enhanced pharmaceutical properties such as increased dissolution rates. Therefore, the second part of this work looks at incorporating metastable drug crystals directly into delivery devices without further processing. This concept involves incorporating a crystallisation ‘dish’ into a dosage device in the form of an individual pore in a substrate or scaffold, so that the required crystal form can be grown in situ. A manufacturing method has been developed to produce polymer scaffolds with a very controlled pore structure by using sugar spheres as a regularly shaped solid porogen. In addition, an image processing technique, based on X-ray microtomography data, is used to fully characterise the resultant scaffolds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available