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    The physical chemistry of corticosteroid-cyclodextrin complexes: The Host-guest Chemistry of Corticosteroid and Cyclodextrin Systems Elucidated with NMR and Applied to Novel Surface-decorated Surface Enhanced Raman Spectroscopic Probes

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    Author
    Eteer, Shahrazad A.
    Supervisor
    Scowen, Ian J.
    Munshi, Tasnim
    Telford, Richard
    Keyword
    Corticosteroids
    HFA
    Complexation
    Cyclodextrins
    Inhalation
    pMDI
    NMR
    SERS
    Nanoparticles
    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    Faculty of Life Sciences
    Awarded
    2018
    
    Metadata
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    Abstract
    Inhaled corticosteroids (ICS) are used to address inflammatory illnesses including asthma and COPD, with delivery commonly achieved using pressurised metered dose inhalers (pMDI). Hydrofluoroalkanes (HFAs) have been introduced as an alternative propellant to chlorofluorocarbons (CFCs) to reduce their environmental impact. However, the thermodynamic properties of HFAs are poorly understood and are different to those of CFCs. It is essential, therefore, to characterise the drugs and excipients used in HFA inhalers in order to obtain a comprehensive understanding of the device performance and the therapeutic efficacy. This work has developed different analytical methods to study the complexation between ICS and CD which are added to enhance the solubility of inhaled drugs in pMDI propellant systems providing rational control of suspension vs. solution formulations and hence their dose uniformity and stability. The Nuclear Magnetic Resonance (NMR) method developed has shown weaker complexation between budesonide and the derivatised CDs DIMEB and TRIMEB in organic solvents compared to D2O with the strength of the complex formed being ranked as D2O > MeOD > CDCl3 > CD3CN. The derivatisation of the CD also shows a marked difference in complexation with budesonide with the strength of the association being ranked as DIMEB > βCD > TRIMEB. Studies of various ICS compounds with TRIMEB in the fluorinated propellant HPFP showed the association to be greatest in budesonide, followed by beclomethasone dipropionate, momestasone furoate and fluticasone propionate. Surface-enhanced Raman scattering (SERS) has been used for the detection of corticosteroids in water using thiol functionalised βCD as a complementary study to NMR. This has been utilised to evaluate the host-guest complexes formed and provides further insight into the complexation of the compounds by their inclusion into the CD cavity. The structural data obtained using the NMR and SERS approaches developed have provided a fundamental insight into the physical chemistry of these interactions at a molecular level.
    URI
    http://hdl.handle.net/10454/17379
    Type
    Thesis
    Qualification name
    PhD
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    Theses

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