Understanding What Happens to Aerosols on Inhalation: Dynamics of Size and Compositional Change
Jonathan P. Reid1, Allen E. Haddrell1, David Lewis2 & Tanya Church2
1School of Chemistry, University of Bristol, Bristol, BS81TS, United Kingdom
2Chiesi Limited, Bath Road Industrial Estate, Chippenham, Wilts, United Kingdom
In inhalation therapies, many microphysical processes can occur on timescales directly comparable to timescales for inhalation and exhalation. The uptake and loss of water, propellant evaporation, co-solvent evaporation, dissolution of crystalline or amorphous particles, and particle coalescence may all occur for newly formed particles emitted from drug delivery devices such as dry powder inhalers (DPIs), metered dose inhalers (MDIs) and nebuliser systems. Although analysis of residual particles can be routinely achieved, many of the processes occurring in the aerosol phase are not amenable to investigation by conventional techniques, requiring the development of new approaches to more fully establish the factors that control aerosol particle deposition, disposition and, ultimately, efficacy. Here, we present microphysical aerosol particle measurements that directly allow access to the timescales, environmental conditions and particle sizes that must be addressed when understanding what happens to aerosol particles from the point of generation to deposition. In particular, we explore the dynamics of water transport, specifically the kinetics of water transport to and from particles during condensational growth or evaporation. To quantify the size-dependent changes that can be expected on inhalation, it is necessary to both determine the capacity of particles to grow by absorbing water as a function of the environmental relative humidity and temperature, and the timescale for particle size change. Thus, we report measurements of the equilibrium growth (the capacity) of a range of typical excipients and pharmaceutical ingredients (e.g. drug, lactose, and other excipients) and the kinetics of water condensation. In addition, we suggest mechanisms by which the timescale of growth can be actively controlled and tuned to be slower than the inhalation/exhalation time.