Directly Probing the Dynamic Behaviour of Particles Originating from DPI and MDI Starting Formulations
Allen Haddrell1, David Lewis2, Tanya Church2, Jonathan Reid1
1University of Bristol, Bristol, UK
2Chiesi Farmaceutici S.p.A., Chippenham, UK
How deep in the respiratory tract a pharmaceutical aerosol penetrates is dependent on the size of the particle at the point of inhalation, its composition, and the microphysical processes that occur during inhalation. The aerosol composition influences the degree to which particles grow when inhaled directly, affecting the deposited dose and pattern. An understanding of the dynamic behaviour of inhalable aerosol is expected to be critical to predicting regional and total dose, which in turn will affect overall efficacy. Meaning, there is the potential to tailor the dynamics of pharmaceutical aerosol, through including trace quantities of additives to the starting formulation, to deliver the desired dose to a specific region in the lung.
Previously, precise measurements of pharmaceutical aerosol’s thermodynamics (e.g. hygroscopic growth from dry to >99% relative humidity (RH)) and dynamic (rapid size change resulting from changes in RH) has been demonstrated for nebulizer formulations. To be presented here is the expansion of this technology to directly measure the dynamic behaviour of aerosol originating from metered dose inhaler (MDI), and dry powder inhaler (DPI) starting formulations. These measurements include: (1) the dissolution, in the aerosol phase, of DPI particles and, (2) the rapid evaporation of volatile species from droplets from MDI starting formulation, to saturated water droplet, to final particle. The time scale for these processes was observed to be on the same order as that of a single breath, meaning they will directly impact their deposition pattern in the lung.