Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model
Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient mul...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/1/61 |
| _version_ | 1797491271814610944 |
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| author | Mohamed Talaat Xiuhua Si Jinxiang Xi |
| author_facet | Mohamed Talaat Xiuhua Si Jinxiang Xi |
| author_sort | Mohamed Talaat |
| collection | DOAJ |
| description | Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions. |
| first_indexed | 2024-03-10T00:45:05Z |
| format | Article |
| id | doaj.art-60dc9b355d214b43b368cd3a88a08b4e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T00:45:05Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-60dc9b355d214b43b368cd3a88a08b4e2023-11-23T15:01:28ZengMDPI AGPharmaceuticals1424-82472022-01-011516110.3390/ph15010061Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract ModelMohamed Talaat0Xiuhua Si1Jinxiang Xi2Department of Biomedical Engineering, University of Massachusetts, Lowell, MA 01854, USADepartment of Aerospace, Industrial, and Mechanical Engineering, California Baptist University, Riverside, CA 92504, USADepartment of Biomedical Engineering, University of Massachusetts, Lowell, MA 01854, USAAccurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.https://www.mdpi.com/1424-8247/15/1/61metered dose inhaler (MDI)press-and-breatheactuation–inhalation coordinationdispersionorificehigh-speed imaging |
| spellingShingle | Mohamed Talaat Xiuhua Si Jinxiang Xi Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model Pharmaceuticals metered dose inhaler (MDI) press-and-breathe actuation–inhalation coordination dispersion orifice high-speed imaging |
| title | Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model |
| title_full | Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model |
| title_fullStr | Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model |
| title_full_unstemmed | Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model |
| title_short | Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model |
| title_sort | effect of mdi actuation timing on inhalation dosimetry in a human respiratory tract model |
| topic | metered dose inhaler (MDI) press-and-breathe actuation–inhalation coordination dispersion orifice high-speed imaging |
| url | https://www.mdpi.com/1424-8247/15/1/61 |
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