Dynamic Response of Hygroscopic Pharmaceutical Aerosol on Inhalation

Abstract

Drug delivery to the lungs using aerosol is a well-established route for treating a wide range of respiratory and systemic diseases. However, the physicochemical processes that transform aerosol between generation and deposition are poorly understood. Control over time-dependent aerosol properties, such as size and composition, could improve the efficacy of inhalation therapeutics by targeted delivery of an active pharmaceutical ingredient (API) to the disease site. Aerosol tools, developed for probing atmospheric aerosol processes, have been applied to study the dynamics of inhalation aerosol. This thesis will provide important insights into factors that govern the capacity and dynamics of hygroscopic growth, influencing where aerosol deposits in the respiratory tract.
This thesis describes laboratory-based techniques that were used to explore the dynamic aerosol processes occurring during and prior to inhalation. An advanced electrodynamic balance (EDB) was designed and developed to replicate the saturated environmental conditions within the lungs. Elastic light scattering methods were used determine the time-dependence of droplet size and phase on evaporation, condensation, crystallisation and dissolution. In addition to single particle measurements, a double ring EDB and falling droplet column (FDC) were used to collect dried aerosol samples prior to scanning electron microscopy (SEM) imaging.
Evaporation measurements on an EDB were used to infer the hygroscopic response of a range of APIs and excipients frequently used in inhalable drug formulations. The influence of environmental conditions, particle morphology, particle composition and particle size on dissolution kinetics of a crystalline particle were investigated. In addition, the effect of drying conditions on crystallisation kinetics of an aqueous droplet are explored. Importantly, it is shown that the time taken for complete dissolution of a crystalline particle is significantly reduced by an increase in particle size and a decrease in the gas phase RH. This thesis draws a comparison between aerosol phase and bulk phase dissolution measurements.

Date of Award	22 Mar 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Jonathan P Reid (Supervisor)