Optimisation of inhaled corticosteroid delivery to asthmatic children: integration of in vitro and in vivo methods

[Truncated abstract] Inhaled corticosteroids (ICS) are the treatment of choice for asthmatic children with persistent symptoms. The inter-relationships between the particle size of ICS, delivery device and inhalation profile can be used to determine the characteristics which optimise the delivery of ICS to children. Gamma scintigraphy has been widely used to assess the total body deposition and regional deposition of radiolabelled ICS from different delivery devices in vivo. Recorded breathing patterns can be transferred to a Flow-Volume Simulator connected to a Next Generation Impactor to measure drug output in vitro. The main aims of this thesis are therefore: to use gamma scintigraphy to determine in vivo biodistribution of ICS with different particle sizes, delivered via pMDI-spacer, with different inhalation techniques; to determine the relationship between delivery device, inhalation profile and variability in lung deposition; to use Flow-Volume Simulation and Next Generation Impaction to predict lung deposition of inhaled corticosteroids from pre-recorded breathing patterns of asthmatic children in vitro. The main hypotheses of this thesis are: that delivery of ICS via small volume pMDI-spacer can be improved by using formulations with a small particle size and a slow single maximal inhalation, followed by a 'breath hold'; that variability in the delivery of ICS to young children can be reduced with a slow single maximal inhalation or with an incentive spacer device with tidal breathing; that inspiratory parameters of the first inhaled breath via small volume pMDI-spacer can be predictive of lung deposition and oropharyngeal and gastrointestinal; that in vivo lung deposition can be predicted in vitro from recorded breathing patterns and Flow-Volume Simulation in tandem with impaction...