In Vitro Evaluation of Medical Gases and Sprays Using Nasal Replicas
Creators: Chen, John
Publisher: name: University of Alberta Library
Year: 2022

<p>The objective of this thesis is to describe two new methodologies for evaluating medical gas and nasal spray delivery, respectively, in vitro using nasal replicas. The first half of the body of thesis describes the development of a new in vitro benchtop method for evaluating the delivery of medical gases across different modalities (e.g. delivery of pulsed vs. continuous flows). The second half describes the design and validation of an idealized nasal replica which mimics the average in vitro and in vivo regional deposition of nasal sprays in adult subjects.<br>
Chapter 1 provides the background and justification for the use of nasal replicas in in vitro evaluations of the delivery of medical gas and nasal sprays. For medical gases, previous researchers have relied on highly simplified geometries, which cannot simulate physiologically accurate pressure changes in the airways during breathing, nor account for the effect of intersubject variability in patient airway geometries on gas delivery. For sprays and aerosols, an extensive history of in vitro studies evaluating regional intranasal deposition using realistic nasal replicas already exists. These studies tend to be performed with a single geometry, which is unlikely to be representative of the population at large, highlighting the potential utility of a standardized idealized geometry which would mimic average regional in vivo and in vitro deposition across an adult population. <br>
Chapter 2 introduces the problem of equivalency between continuous flow and pulse flow delivery of supplemental oxygen and describes the development of a predictive in vitro model for inhaled oxygen delivery using a set of realistic nasal airway replicas.<br>
Experiments are reported to compare pulse flow delivery from a commercial portable oxygen concentrator (POC) with continuous flow from a compressed oxygen cylinder. A volume-averaged fraction of inspired oxygen (FiO2) was calculated by numerically integrating inhaled oxygen flow rates sampled at the exit of each replica and used as a common basis for comparison between continuous and pulse flow. Pulse flow delivered consistently lower FiO2 than continuous flow rates equivalent to nominal pulse flow settings. To the extent that the POC triggered successfully at the start of inhalation, intersubject variability in airway geometries had a minimal effect on FiO2. Testing using airway replicas was also useful in identifying cases of impaired device function or failure.<br>
Chapter 3 investigates the relative performance of four POCs both against each other and against continuous flow oxygen using a single realistic nasal replica which had a reliably high triggering pressure and which delivered a medium FiO2 compared to the full replica set. Oxygen delivery to the deep lung was also analyzed in silico by combining in vitro oxygen concentration waveforms over time and a single-path mathematical model of the lungs. Significant differences in POC performance based on FiO2 were found between continuous and pulse flow, and between pulse modes in different POCs at the same nominal device setting. In silico simulations revealed that while pulse flow is a more efficient mode of delivery than continuous flow, continuous flow ultimately delivers a greater volume of oxygen per breath.<br>
Chapter 4 describes the manufacture and in vitro validation experiments needed for the development of an idealized nasal replica, based on a geometry previously developed using in silico simulations. This replica, manufactured in plastic, was validated by comparing with regional deposition in realistic, sectioned nasal replicas obtained from in vitro deposition experiments and in previously published in vivo data. A commercial nasal spray pump was actuated repeatably into each realistic or idealized nasal replica under a steady inspiratory flow at two different orientations. It was found that regional deposition in the idealized replica agreed well with average regional deposition in the realistic replicas and with previously published in vivo gamma scintigraphy data.<br>
In Chapter 5, an aluminum version of the idealized nasal replica from Chapter 4 was used in order to facilitate further in vitro experiments with a wider set of intranasal drug formulations (one aqueous solution, one aqueous suspension and one propellant-based formulation). Good agreement was seen between deposition measured using the idealized replica and in vivo deposition patterns for all three nasal drug formulations that were tested.<br>
Chapter 6 summarizes the main conclusions of the thesis and provides possible directions for future research.</p>