Abstract
Background andobjective: Understanding the impact of inhaler resistance on particle transport anddeposition in the human upper airway is essential for optimizing inhalerdesigns, thereby contributing to the enhancement of the therapeutic efficacy ofinhaled drug delivery. This study demonstrates the potential effects of inhalerresistance on particle deposition characteristics in an anatomically realistichuman oropharynx and the United States Pharmacopeia (USP) throat usingcomputational fluid dynamics (CFD).
Method: Magnetic resonance(MR) imaging was performed on a healthy volunteer biting on a small mockupinhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiecewere reconstructed from the MR images. CFD simulations coupled with discrete phasemodelling were conducted. Inhaled polydisperse particles under two differenttransient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and60 L/min were investigated. The effect of inhaler mouthpiece resistance wasmodelled as a porous medium by varying the initial resistance (Ri) and viscousresistance (Rv). Three resistance values, 0.02 kPa0.5minL−1,0.035 kPa0.5minL−1 and 0.05 kPa0.5 minL−1,were simulated. The inhaler outlet velocity was set to be consistent across allmodels for both flow rate conditions to enable a meaningful comparison ofmodels with different inhaler resistances.
Result: The results from this study demonstrate that investigating the effect ofinhaler resistance by solely relying on the USP throat model may yieldmisleading results. For the geometrically realistic oropharyngeal model, boththe pressure and kinetic energy profiles at the mid-sagittal plane of theairway change dramatically when connected to a higher-resistance inhaler. Inaddition, the geometrically realistic oropharyngeal model appears to have aresistance threshold. When this threshold is surpassed, significant changes inflow dynamics become evident, which is not observed in the USP throat model.Furthermore, this study also reveals that the impact of inhaler resistance in ageometrically realistic throat model extends beyond the oral cavity and affectsparticle deposition downstream of the oral cavity, including the oropharynxregion.
Conclusion: Results from this study suggest that key mechanisms underpinning theworking principles of inhaler resistance are intricately connected to theircomplex interaction with the pharynx geometry, which affects the localpressure, local variation in velocity and kinetic energy profile in the airway.
Original language | English |
---|---|
Article number | 107673 |
Pages (from-to) | 1-13 |
Number of pages | 13 |
Journal | Computers in Biology and Medicine |
Volume | 167 |
Early online date | 10 Nov 2023 |
DOIs | |
Publication status | Published - Dec 2023 |
Bibliographical note
Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- Computational fluid dynamics
- Dry powder inhalers
- Inhaler resistance
- Particle deposition