Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays
Abstract
:1. Introduction
2. Results
2.1. Model Development for MDI Delivery
2.1.1. MDI-Airway Geometry
2.1.2. Modeling of Spray Aerosols during Actuation
2.1.3. Inhalation Waveforms: Control and Variants
2.1.4. Computational Mesh
2.2. Characterization of MDI Actuation
2.2.1. Imaging of MDI Sprays
2.2.2. Reverse Identification of Orifice Discharge Velocity
2.3. Flow and Aerosol Dynamics in Airway: Control Case (QMax = 60 L/min)
2.3.1. Airflow Dynamics
2.3.2. Spray Droplet Dynamics
2.4. Effects of Breathing Depth
2.4.1. Variation in Airflows
2.4.2. Surface Deposition of MDI Droplets
2.4.3. Deposition Fraction (DF) and Penetration Rate (PR) vs. Time
2.4.4. Deposition Enhancement Factor (DEF)
3. Discussion
4. Materials and Methods
4.1. MDI and Airway Models
4.2. High-Speed Imaging and Image Analysis
4.3. Numerical Methods
4.3.1. Boundary Conditions
4.3.2. Experiment-Based Estimation of the Spray Discharge Speed
4.3.3. Flow and Particle Transport Simulations
5. Conclusions
- The initial velocity of the spray plume from the ProAir-FHA actuator orifice was predicted to be 26 m/s, which matched the measured velocities at 3 and 6 cm from the mouthpiece.
- The LES-Lagrangian predicted spray plume topologies into the open-air agreed well with corresponding high-speed images both temporally and spatially.
- The drug loss in the device itself peaked at 45–60 L/min, while that in the mouth constantly increased with the inhalation depth from 15 to 75 L/min.
- The pulmonary drug delivery efficiency (beyond G9) had a negative relationship with the inhalation rate, with a predicted penetration rate of 11.4% at PIFR of 60 L/min, 30.7% at 30 L/min, and 45.7% at 15 L/min.
- Model cross-validation with existing experiments indicates a high dosimetry sensitivity to initial spray properties (size and velocity) and transient inhalation rate, which should be correctly considered in numerical modeling for accurate dosimetry predictions.
- This study has not reached the most efficient way of inhalation for optimal ProAir delivery yet; however, improved personalized inhalation therapy can be achieved by matching the inhaler type with the patient’s disease and breathing capacity.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Talaat, M.; Si, X.A.; Xi, J. Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays. Pharmaceuticals 2022, 15, 706. https://doi.org/10.3390/ph15060706
Talaat M, Si XA, Xi J. Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays. Pharmaceuticals. 2022; 15(6):706. https://doi.org/10.3390/ph15060706
Chicago/Turabian StyleTalaat, Mohamed, Xiuhua April Si, and Jinxiang Xi. 2022. "Lower Inspiratory Breathing Depth Enhances Pulmonary Delivery Efficiency of ProAir Sprays" Pharmaceuticals 15, no. 6: 706. https://doi.org/10.3390/ph15060706