Expanding the Performance and Functionality of Air-Jet Dry Powder Inhalers Across Multiple Applications

Abstract

This dissertation aims to expand the performance and functionality of air-jet dry powder inhaler (DPI) applications through the development of a next-generation, mesh-nebulizer-based, and scalable spray dryer for the production of pharmaceutical aerosols, along with new spray-dried formulation production methods, novel formulations, and new air-jet DPI components for aerosol delivery to both infants and adults. The first aim focused on the development of a custom small-particle spray drying system capable of integrating vibrating mesh nebulizer technologies in various configurations for the production of excipient enhanced growth (EEG) formulations. This flexible system enabled efficient production of both small- and large-particle powders for pulmonary and nasal-targeted drug delivery. Additional advantages of the developed spray dryer included a significant increase in production rates using dual- and triple-mesh nebulizer configurations. Formulations produced in this work included a synthetic lung surfactant formulation (SLS-EEG), which demonstrated improved aerosol performance with a fine particle fraction (FPF < 5 µm) of 89.9% and a reduction in pre-separator loss from 30% to 6% when tested using the Next Generation Impactor (NGI) and compared with powder previously produced using the commercial Buchi B-90 Nano Spray Dryer.

The second aim of this work focused on the development and evaluation of an infant manual cyclic (MC) air source for operating air-jet DPIs, delivering consistent and repeatable low air volumes (up to 17 mL) in compliance with Lung Ventilator Code ISO 10651-4 when the device is paired with an infant air-jet DPI. A compact version of the MC air source was also developed for various air-jet DPI applications, including nasal-targeted delivery.

Together, these aims advanced the performance of air-jet DPIs through the development of a scalable and mesh-nebulizer based spray dryer capable of producing efficient EEG formulations, and the development of new DPI components suitable for both pediatric and adult populations.