Author ORCID Identifier

0000-0002-1570-9798

Defense Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Mechanical and Nuclear Engineering

First Advisor

P. Worth Longest

Second Advisor

Michael Hindle

Third Advisor

Laleh Golshahi

Fourth Advisor

Wei-Ning Wang

Fifth Advisor

Ram Gupta

Abstract

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) system delivered 71.6% of the nebulized dose to the tracheal filter of adult simulated subjects (Table 4.5) and successfully passed an initial human subject safety study. A second focus created a Heated Dryer System (HDS) from similar concepts as the LVMH but designed for unsteady flows such as direct oral breathing. System aerosol delivery efficiency of approximately 90% to the tracheal filter of a simulated adult subject was found for the HDS (Table 8.2). A jump in high-performance liquid chromatography (HPLC) recovery from ~85% for the LVMH to near total recovery of the nebulized dose for the HDS suggest a limited production of fugitive aerosol emission from the filtered HDS flow pathway (Tables 4.5 and 8.2). A third segment of work focused specifically on the production of EEG powders with vibrating mesh nebulizers for use in dry powder inhalers (DPIs). The developed VCU Small Particle Spray Dryer achieved production of powders with similar performance in a novel DPI as powders produced in a commercial lab-scale spray drying system (Table 9.4). Notably, the developed spray dryer was a fraction of the cost and contained expandable capacity for future experimental needs.

Rights

© Benjamin M. Spence

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-13-2021

Available for download on Tuesday, December 13, 2022

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