Single particle mass spectrometry techniques were applied to the analysis of aerosol
particles originating from inhaler devices, used to deliver pharmaceuticals for the
treatment of lung disease such as asthma.The inhalation products studied were Seretide® for which the formulated drug product
is composed of a blend of fluticasone propionate (FP) which is a corticosteroid and
salmeterol xinofoate (SX) which is a long acting f3- agonist. It has been suggested
previously that the formation of particles that are composed of both FP and SX by coassociation can give improved efficacy: however in the past it has been difficult to
analyze this type of co- associated particle. Hence, the purpose of the work described
in this thesis was to develop single particle mass spectrometry methods that could
assess the degree of co- association between FP and SX in fine aerosolized particles
emitted from the inhaler devices.Two types of inhaler device were investigated and these were pressurized metered
dose inhalers ( pMDIs) and dry powder inhalers (DPIs). The formulated product for
pMDIs was a blend of FP and SX held in a suspension of propellant in a pressurized
canister. The formulated product for the DPIs is comprised of a blend of FP and SX
and an excipient lactose.Two commercial single particle mass spectrometers were used in this work; an
Aerosol Time -of- Flight Mass Spectrometer (TSI, Shoreview, MN, USA) and an
Aerodyne Aerosol Mass Spectrometer (Aerodyne, Billerica, MA, USA). Although the
general layout of these instruments was similar in that they are both comprised of an
inlet, a particle sizing region and a mass spectrometer, there were some differences in
their design. For example, the ionization source of the Aerosol Time -of- Flight Mass
Spectrometer used a single step process involving laser ablation and ionization while
the Aerodyne Aerosol Mass Spectrometer used a two step process involving thermal
desorption from a hot plate followed by electron ionization. These instruments were
compared and evaluated in terms of their design and the characteristics of the data
acquired on aerosols of pharmaceutical materials.Data analysis methods for single particle mass spectrometry were developed based on
the mass spectrometric fragmentation patterns indicative of either pure or coassociated particles. Data analysis was performed by either using representative ions
from the mass spectrum taken from each particle or by using multivariate statistical
analysis as a pattern recognition tool applied to the complete mass spectrum for each
particle.High levels (above 50 %) of co- association were found in the emitted doses from both
pMDI and DPI products. Although the design of each instrument was different,
reasonable agreement in the levels of co- association was found as long as the size of
particle that was analyzed by the mass spectrometer in each case was taken into
account.Finally a comparison of the applicability of each of the commercial single particle
mass spectrometers to the analysis of materials taken from pharmaceutical aerosols
was made. Recommendations for future work on instrument development and further
applications for inhalation products are given
