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Title: Nanoparticle formulations in HFA propellants
Author: Ridder, Kristin Barbara
ISNI:       0000 0001 3518 272X
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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With the enforcement of the Montreal Protocol on ozone depleting gases, non-ozone depleting hydrofluoroalkanes (HFAs), i.e. HFA-134a and HFA-227ea, are now replacing the ozone depleting chlorofluorocarbon (CFC) propellants in pressurized metered-dose inhalers (pMDIs). The transition has proven to be difficult due to differences in the physical and chemical properties, e.g. higher polarity and higher vapour pressure. Since commonly used surfactants in CFC pMDIs, i.e. Span 85, oleic acid and lecithin are effectively insoluble in HFAs, a surfactant solubility study was carried out in this work in order to find HFA soluble surfactants. Further on, surfactant solubility in HFA-134a and HFA-227ea was compared with those in 2H,3H-decafluoropentane in order assess the latters suitability as a model propellant. This was followed by UV/VIS and fluorescence spectroscopic investigations into surfactant aggregation and aggregate orientation in HFA propellants. Beclomethasone dipropionate (BDP) nanoparticles were formulated from an emulsion template and dispersed in HFA-227ea with the aim of improving pulmonary drug deposition efficiency and drug targeting to smaller airways. In vitro drug deposition profiles of BDP nanoparticle suspension pMDIs were determined using Andersen Cascade impaction and compared to a commercially available BDP suspension CFC pMDI (Becotide) and a BDP solution phase HFA pMDI (Qvar). Furthermore, the stability of BDP nanoparticle suspension pMDIs at elevated conditions was assessed. Soluble surfactants could be found among the polyoxyethylene-ethers and poly (ethylene oxide)-poly (propylene oxide) block copolymers. 2H,3H-decafluoropentane has proven to be a good model propellant for HFA-134a only. The investigations into surfactant behaviour in HFA propellants suggests a stepwise aggregation of L1 orientated surfactant aggregates. Depending on formulation variables, e.g. drug concentration, surfactant concentration and the addition of cosolvent, an improved drug deposition profile compared to the microparticle CFC pMDI was shown for BDP nanoparticle pMDIs. The addition of polyvinylpyrrolidone (PVP) to the nanoparticle suspension proved to reduce particle growth, thus improved pMDI stability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available