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dc.contributor.advisorKelly, Adrian L.
dc.contributor.advisorParadkar, Anant R.
dc.contributor.advisorGough, Timothy D.
dc.contributor.authorWood, Clive John*
dc.date.accessioned2018-01-19T13:06:56Z
dc.date.available2018-01-19T13:06:56Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10454/14580
dc.description.abstractThis project utilised a novel solvent-free continuous cocrystallisation (SFCC) method to manufacture pharmaceutical co-crystals. The objectives were to optimize the process towards achieving high co-crystal yields and to understand the behaviour of co-crystals under different conditions. Particular attention was paid to the development of near infrared (NIR) spectroscopy as a process analytical technology (PAT). Twin screw, hot melt extrusion was the base technique of the SFCC process. Changing parameters such as temperature, screw speed and screw geometry was important for improving the co-crystal yield. The level of mixing and shear was directly influenced by the screw geometry, whilst the screw speed was an important parameter for controlling the residence time of the material during hot melt extrusion. Ibuprofen – nicotinamide 1:1 cocrystals and carbamazepine – nicotinamide 1:1 co-crystals were successfully manufactured using the SFCC method. Characterisation techniques were important for this project, and NIR spectroscopy proved to be a convenient, accurate analytical technique for identifying the formation of co-crystals along the extruder barrel. Separate thermal and model shear deformation studies were also carried out to determine the effect of temperature and shear on co-crystal formation for several different pharmaceutical co-crystal pairs. Finally, NIR spectroscopy was used to create two partial least squares regression models, for predicting the 1:1 co-crystal yield of ibuprofen – nicotinamide and carbamazepine – nicotinamide, when in a powder mixture with the respective pure API. It is believed that the prediction models created in this project can be used to facilitate future in-line PAT studies of pharmaceutical co-crystals during different manufacturing processes.en_US
dc.description.sponsorshipEngineering and Physical Sciences Research Council (EPSRC)en_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>.eng
dc.subjectHot melt extrusion; Co-crystal; Near infrared (NIR) spectroscopy; Model shear; Twin screw extrusion; Quantification; Partial least squares; Solvent-free; Continuous cocrystallisationen_US
dc.titleInvestigation of a solvent-free continuous process to produce pharmaceutical co-crystals. Understanding and developing solvent-free continuous cocrystallisation (SFCC) through study of co-crystal formation under the application of heat, model shear and twin screw extrusion, including development of a near infrared spectroscopy partial least squares quantification methoden_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentSchool of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2016
refterms.dateFOA2018-07-28T02:30:09Z


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