A Novel Method for Investigating Plume Dynamics and Hygroscopicity in Therapeutic Aerosols

Abstract

Aerosol-based drug delivery to the lungs is widely used to treat respiratory diseases, as it provides direct access to the respiratory tract. However, the complex transformations that aerosol particles experience from generation to deposition remain incompletely understood. This thesis employs advanced aerosol measurement techniques to explore these transformations, with a focus on how relative humidity and particle composition affect the behaviour and deposition of inhaled aerosols, ultimately enhancing therapeutic efficacy in pulmonary drug delivery.
In this work, a novel Tandem Aerosol Particle Sizer (TAPS) technique is employed to examine the temporal variations in particle size distributions of therapeutic aerosols at different RH levels, simulating both ambient and lung-like conditions. The TAPS method offers high time-resolution data and simultaneously measures particle size distributions at two RHs. These dual measurements allow for precise assessment of how RH influences aerosol size dynamics. Comparative Kinetics-Electrodynamic Balance (CK-EDB) measurements complement TAPS data, providing insight into plume dynamics based on single-droplet behaviour. Additionally, this thesis examines the hygroscopic growth behaviour of various nebulized pharmaceutical formulations—mannitol, trehalose, salbutamol, and tobramycin—by correlating single-droplet growth factors with aerodynamic properties observed in aerosolized particles. The influence of formulation composition is further analysed by exploring how ethanol content impacts particle size and mass in aerosols generated by the Respimat® Soft Mist Inhaler (SMI).
Together, these findings emphasize the critical role of formulation and environmental conditions in shaping aerosol properties for optimized pulmonary drug delivery.

Date of Award	18 Mar 2025
Original language	English
Awarding Institution	University of Bristol
Sponsors	Chiesi Farmaceutici S.p.A, Chippenham & EPSRC Centre in Doctoral Training in Aerosol Science
Supervisor	Jonathan P Reid (Supervisor) & Rachael E H Miles (Supervisor)