Dynamic Change of Hygroscopic Spiriva Respimat Aerosol Passing Through a Cascade impactor: Single Particle Measurements and a Deposition Simulation

Natalie Armstrong Green



Cascade impactors are often used to measure the deposition fraction of an ensemble of particles across a range of stages all varying in size. However, particle sizes can often be dynamic during aerosolisation and inhalation, behaviour that cannot be resolved by impactors, but which may significantly impact on the recorded deposited fractions in different stages. The dynamic processes experienced by particles on inhalation into the humid lungs, where the relative humidity often exceeds 99.5%, can significantly change particle size distributions, with particles growing by water condensation. There are currently three main delivery devices used for administering aerosolised drugs to the lung, MDIs, DPIs and nebulisers. Respimat® is a new type of inhaler used for respiratory drugs and, with a precisely engineered nozzle, it generates a soft mist containing a high fine particle fraction of liquid aerosol. In these measurements, a cascade impactor was used to measure the fractionated particle masses of Spiriva Respimat® (API tiotropium bromide aerosol) at various sampling RHs, with the aerosol generated initially at high water content. Measurements are compared with simulations that account for the dynamics of size change during the passage of the aerosol through the cascade impactor, responding to the different sampling RHs. The dynamics are based on measurements of the individual droplet evaporation and condensation kinetics of the solution in Spiriva Respimat® under the same RH conditions. This cascade impactor model allows the hygroscopic properties of the substance to be applied to the dynamics as a function of time, sampling RH and the initial particle size distribution. The results of the cascade impactor simulations show good agreement with experimental data. Such an approach could be used for a range of APIs and formulations delivered by Respimat®, both in aqueous and ethanolic solutions.

Key Message

A simulation cascade impactor has been developed including dynamic changes of aerosol during transport, where evaporation and condensation depend on relative humidity. The model is based on the hygroscopic response of single particles formed from the Spiriva Respimat ® solution. The simulated data matches well with experimental cascade impactor results.

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