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dc.contributor.advisorIsreb, Mohammad
dc.contributor.authorBright, Andrew G.
dc.date.accessioned2018-05-18T09:25:30Z
dc.date.available2018-05-18T09:25:30Z
dc.date.issued2015
dc.identifier.urihttp://hdl.handle.net/10454/15943
dc.description.abstractThis dissertation has focused on studying the effect of four glycine derivatives on the solid state properties of mannitol, glycine, and sucrose when freeze dried into blended mixtures. The primary goal was to assess their value for use in the stabilisation of vaccines in the solid state, by examining key physical and chemical characteristics, which have been documented to be beneficial to the stabilisation of biopharmaceutical formulations. The novel excipients; dimethyl glycine, and trimethyl glycine, were shown to retard the crystallisation and increase the overall glass transition temperature, of mannitol, when freeze dried as evidenced by DSC and Powder X-ray diffraction. Mannitol’s glass transition temperature increased from 100C to 12.650C and 13.610C when mixed with methyl-glycine and dimethyl glycine respectively. The glycine derivatives did not show the same effect on sucrose which remained amorphous regardless of the concentration of the other excipient. The different behaviour with the sucrose system was thought to be due to relatively high glass transition temperature of sucrose. Conversely glycine remained highly crystalline due it’s relatively low glass transition temperature. The novel excipient formulations were also assessed for their effect on the aggregation of the adjuvant aluminium hydroxide when freeze dried by Dynamic Light Scattering (DLS).The formulations containing the glycine derivatives all caused a decrease in the aggregation size of the adjuvant from ~26 μm, to 185 nm in the presence of methyl glycine. The effects of lysozyme and viral antigen on the adjuvants were also examined showing that the addition of the virus did not affect the size of the aggregates formed, however lysozyme showed significant decreases in the aggregates formed. Examination of the freezing method were also made showing that faster freezing rates produced smaller aggregates of the adjuvant. When investigating the rate at which the excipients lost water during secondary drying there was evidence of the formation of hydrates of glycine, trimethyl glycine, and mannitol has shown that the glycine derivatives have attributes which would be beneficial in stabilising vaccines in the solid state when freeze dried.en_US
dc.description.sponsorshipStabilitech Ltd. and the Engineering 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.subjectFreeze dryingen_US
dc.subjectGlycine derivativesen_US
dc.subjectDifferential scanning calorimetry (DSC)en_US
dc.subjectPowder X-Ray diffraction (P-XRD)en_US
dc.subjectRaman spectroscopyen_US
dc.subjectCrystallisationen_US
dc.subjectWater lossen_US
dc.subjectVaccinesen_US
dc.subjectAdjuvanten_US
dc.subjectStabilisationen_US
dc.subjectAmorphousen_US
dc.subjectGordon-Taylor equationen_US
dc.subjectSolubility parametersen_US
dc.subjectKarl Fischeren_US
dc.subjectExcipientsen_US
dc.subjectProteinsen_US
dc.subjectDLS (Dynamic Light Scattering)en_US
dc.subjectPolymorphsen_US
dc.subjectVaccinesen_US
dc.subjectFormulationen_US
dc.subjectMannitolen_US
dc.subjectSucroseen_US
dc.subjectBiopharmaceuticalsen_US
dc.titleMechanistic Insights into the Stabilisation of Biopharmaceuticals using Glycine Derivatives. The Effect of Glycine Derivatives on the Crystallisation, Physical Properties and Behaviour of Commonly used Excipients to Stabilise Antigens, Adjuvants and Proteins in the Solid Stateen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentSchool of Pharmacy, Faculty of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2015
refterms.dateFOA2018-07-29T02:03:16Z


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