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Title: Surfactant-mediated surface modification of microparticles for pressurised metered dose inhalation
Author: Beausang, Emma Louise
ISNI:       0000 0004 2685 2711
Awarding Body: University College London
Current Institution: University College London (University of London)
Date of Award: 2005
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The necessary phase-out of CFC propellants and their replacement with HFA propellants has re-awakened an interest in the formulation science of pMDI suspension formulations, largely driven by the need to identify novel surfactants as a result of the altered physicochemical properties of HFA propellants with respect to CFCs. The aims of this thesis were to explore the validity of using surfactants with a low solubility in HFA propellants as stabilising agents in pMDI HFA suspension formulations, and in so doing to investigate the relationship between powder surface energy and suspension performance within these systems. Adsorption of a range of non-ionic surfactants to the surface of a model hydrophilic drug, terbutaline sulphate (TS), was achieved and the performance of corresponding pMDI suspension formulations was investigated. Surfactant adsorption was found to improve pMDI suspension stability by reducing phase separation and particle aggregation. The improvement in suspension performance was linked to a reduction in both the dispersive and acidic components of powder surface energy following surfactant adsorption. Similar adsorption experiments were carried out using a model hydrophobic drug, budesonide. While surfactant adsorption to the drug surface succeeded in reducing powder surface energy values, the anticipated improvement in pMDI suspension performance was not observed. Surfactant adsorption did however reduce the amount of suspended material adhered to the container wall. The effect of surfactant adsorption to both drugs on pMDI suspension formulations over extended storage periods was investigated. Adsorption of a hydrophobic poloxamer surfactant to the surface of TS was seen to confer a limited protective effect against water-induced instability in pMDI suspension systems. In the case of budesonide, reduced adhesion to the container wall was seen in all surfactant-containing formulations when compared with controls. Attempts to correlate surface energy with adhesion were complicated by the necessary use of two separate methods for surface energy determination. Work in this thesis has confirmed that surfactants with a low solubility in HFA propellants may be considered as potential stabilisers in pMDI suspension systems, and a greater understanding of the role played by surface energy in the performance of these systems has been achieved.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available