DOI
https://doi.org/10.25772/429V-CG42
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
Included in
Aerodynamics and Fluid Mechanics Commons, Biomechanical Engineering Commons, Biomedical Devices and Instrumentation Commons, Computer-Aided Engineering and Design Commons, Electro-Mechanical Systems Commons, Fluid Dynamics Commons, Investigative Techniques Commons, Medicinal Chemistry and Pharmaceutics Commons, Medicinal-Pharmaceutical Chemistry Commons, Nanomedicine Commons, Nanoscience and Nanotechnology Commons, Pharmaceutical Preparations Commons, Pharmaceutics and Drug Design Commons, Pulmonology Commons, Respiratory System Commons, Respiratory Tract Diseases Commons, Systems and Integrative Engineering Commons, Systems Engineering Commons, Therapeutics Commons, Virus Diseases Commons