DOI

https://doi.org/10.25772/3YDB-N942

Defense Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Mechanical and Nuclear Engineering

First Advisor

Dr. Worth Longest

Second Advisor

Dr. Michael Hindle

Third Advisor

Dr. Laleh Golshahi

Fourth Advisor

Dr. Rebecca Heise

Fifth Advisor

Dr. Sheng-Chieh Chen

Abstract

The goal of this research project was to develop an infant air-jet dry powder inhaler (DPI) platform for high-efficiency nose-to-lung (N2L) aerosol administration to infants through optimization of individual system components followed by expansion of the system to higher doses and different formulations using a new approach. Primary challenges associated with aerosol delivery to infants using the N2L route include the extremely narrow extrathoracic airways, short inspiratory times (~0.2 sec), low safe airway pressure (H2O), and very low volumes of air (~10 mL) available to form the aerosol. The infant air-jet DPI system was comprised of three main components: an air source, a small volume turbulence-based aerosolization engine (referred to as the air-jet DPI), and nasal interface; which form the “Infant Air-Jet DPI Platform”. The platform efficiently aerosolized spray-dried powder formulations with conditions safe for infant inhalation to provide lung targeted delivery of inhaled therapeutics utilizing the excipient enhanced growth (EEG) approach, which has previously been developed at VCU. In vitro experiments utilized preterm infant (estimated 1600 g) nose-throat (NT) airway geometries.

Overall, the results of this study have produced an infant air-jet DPI platform that can safely (based on presented metrics) and rapidly (expected full dose delivery in under 3 minutes) deliver a variable (estimated 10 – 100 mg) dose of dry powder formulation with high efficiency (~45 – 60%) to preterm infants (1600 g in vitro model) with consistent performance across multiple formulations via passive metering element configurations, which has not been previously achieved.

Rights

© Connor Matthew Howe

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-7-2022

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