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dc.contributor.advisorBlagden, Nicholas
dc.contributor.advisorStorey, Richard
dc.contributor.authorBerry, David J.*
dc.date.accessioned2011-07-06T14:38:37Z
dc.date.available2011-07-06T14:38:37Z
dc.date.issued2011-07-06
dc.identifier.urihttp://hdl.handle.net/10454/4932
dc.description.abstractThe crystalline solid state is invaluable to both the pharmaceutical and fine chemical sectors. The advantages primarily relate to reducibility criteria required during processing of stable solid state materials and delivering purification, which is inherently performed by the crystal growth process. A major challenge is achieving control through crystallising solids with the desired physico-chemical properties. If this can be achieved the crystalline solid is of great financial and practical benefit. One emerging methodology for manipulating the solid crystalline form is the application of co-crystals. This work relates to key steps in the understanding of rational design of co-crystals utilizing crystal engineering concepts to determine systems before then applying screening criteria to the selected sub-set. Co-crystal screening is routinely undertaken using high-throughput solution growth. We report a low- to medium-throughput approach, encompassing both a melt and solution crystallization step as a route to the identification of co-crystals. Prior to solution studies, a melt growth step was included utilizing the Kofler mixed fusion method. This method allowed elucidation of the thermodynamic landscape within the binary phase diagram and was found to increase overall screening efficiency. This led to the discovery of a number of co-crystal systems with the co-former nicotinamide, with the single crystal structures determined for the following systems; R/S ibuprofen: nicotinamide, S ibuprofen: nicotinamide, R/S flurbiprofen: nicotinamide and salicylic acid: nicotinamide. To assess the crystallization and phase behaviours of determined co-crystals the R/S ibuprofennicotinamide system was selected and successful studies were undertaken determining the aqueous ternary phase behavior and the pre-nucleation speciation in methanol. There have, as yet, been a limited number of published examples which are concerned with pharmaceutical property enhancement by co-crystals, as vast proportion of the literature concerns the growth and isolation of these novel phases. To elucidate further the pharmaceutical relevance of co-crystals the properties of the R/S ibuprofen- nicotinamide system were then assessed showing a positive profile for this material.en_US
dc.description.sponsorshipAstraZeneca and the University of Bradforden_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.en_US
dc.subjectPharmaceuticalen_US
dc.subjectCo-crystalsen_US
dc.subjectDesignen_US
dc.subjectThermalen_US
dc.subjectMicroscopyen_US
dc.subjectScreeningen_US
dc.subjectNicotinamideen_US
dc.subjectIbuprofenen_US
dc.subjectCrystal engineeringen_US
dc.titlePharmaceutical Co-crystals. Combining thermal microscopy and phase space considerations to facilitate the growth of novel phases.en_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentSchool of pharmacyen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2009
dc.description.publicnotesThe accompanying "Experimental raw data files and cifs" are not available online.en
refterms.dateFOA2018-07-19T05:35:48Z


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