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Characterisation of non-crystalline pharmaceuticals (ionic liquids/liquid crystals) by NMR spectroscopy
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Mann, Sarah Kate (2020) Characterisation of non-crystalline pharmaceuticals (ionic liquids/liquid crystals) by NMR spectroscopy. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3520013
Abstract
Non-crystalline forms of pharmaceuticals (ionic liquids/liquid crystals) offer tremendous scope for alteration of the physicochemical and pharmacokinetic properties of drugs with otherwise non-ideal properties. The pharmaceutical industry currently relies predominantly on solid-state crystalline therapeutics, for which a standard set of characterisation methods is available. However, such methods (e.g., X-ray crystallography) are not applicable to liquid therapeutics. In order to facilitate the transition of non-crystalline forms of pharmaceuticals from laboratory to the market, routine methods for their characterisation are required. The overall aim of the work presented in this thesis is to develop such methodology and build on the knowledge of the microscopic/molecular structures and dynamics of ionic liquid (IL), deep eutectic solvent (DES) and liquid crystal (LC) materials used in pharmaceutical applications.
Nuclear magnetic resonance (NMR) is a powerful probe of the local atomic environment and intermolecular interactions (e.g., hydrogen bonding) and can also provide detailed information on molecular dynamics. Thus, NMR is the primary technique utilised in this thesis. Specifically, 1H solution-state and 1H and 13C magic angle spinning (MAS) NMR experiments have been employed to provide insight into the diffusivity, intermolecular interactions between active pharmaceutical ingredients (APIs), exchange processes and reorientational dynamics in a range of pharmaceuticals and model systems.
It is demonstrated that for a series of protic ILs, small changes in structure (hydrogen bonding ability, alkyl chain length and degree of branching) strongly influence the bulk properties (proton transfer, ionicity, viscosity and conductivity). Such properties are dependent on the molecular structure of the constituents and nature of the the inter-ionic interactions. Key hydrogen bonding interactions are directly detected for a model DES composed of two APIs, lidocaine and ibuprofen, by two-dimensional 1H-1H NOESY and ROESY MAS NMR experiments. The hydrogenbonding dynamics are qualitatively determined by following the chemical exchange between the labile protons by means of variable temperature 1H MAS NMR linewidth analysis. Insight into the nature and strength and dynamics of hydrogen bonding is also obtained for an IL composed of choline and geranate (CAGE) and a series of six structural analogues from the 1D 1H MAS NMR spectra. Fast proton exchange is revealed by a single resonance for the carboxylic acid and hydroxyl protons, while the temperature dependence of the 1H chemical shift of
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QC Physics Q Science > QD Chemistry |
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Library of Congress Subject Headings (LCSH): | Liquid crystals, Liquid crystals -- Therapeutic use, Nuclear magnetic resonance spectroscopy, Eutectics | ||||
Official Date: | June 2020 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Physics | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Brown, Steven P. ; Lewandowski, Józef R | ||||
Format of File: | |||||
Extent: | xviii, 232 leaves : illustrations | ||||
Language: | eng |
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