In recent years, pulmonary diseases have posed severe health problems because of increasing air pollution. Some of the promising drug delivery devices for administering the active pharmaceutical ingredients through the pulmonary route include a pressurized metered-dose inhaler and dry powder inhaler (DPI) for the management of respiratory illness. The drug settling (deposition) efficiency in different regions of a human respiratory tract (HRT) for different drug particle sizes is computed using the discrete phase model in the current study. A computer tomography-based realistic HRT replica is used for this purpose with different inhalation rates following a realistic inhalation profile through the DPI device. Unsteady flow analysis is carried out in a human respiratory system up to the sixth-generation bronchi. The particle force balance equation is used in the discrete-phase model to simulate the motion of drug particles in the HRT. Low, moderate, and high inhalation rates following realistic inhalation profiles are used in the present study. The particles of larger size are deposited more in the oral cavity and are deposited higher at a higher inhalation rate due to higher inertia force. It is also observed that drug particle size plays a key role in drug delivery through dry powder inhalers. It is also found that drugs should contain smaller-sized particles (called fine particles) to enable their reach in the distal bronchi.
References
1.
Ahookhosh
, K.
, Yaqoubi
, S.
, Mohammad Pourfard
, M.
, Hamishehkar
, H.
, and Aminfar
, H.
, “Experimental investigation of aerosol deposition through a realistic respiratory airway replica: An evaluation for MDI and DPI performance
,” Int. J. Pharm.
566
, 157
–172
(2019
).2.
Atzeni
, C.
, Lesma
, G.
, Dubini
, G.
, Masi
, M.
, Rossi
, F.
, and Bianchi
, E.
, “Computational fluid dynamic models as tools to predict aerosol distribution in tracheobronchial airways
,” Sci. Rep.
11
(1
), 1109
(2021
).3.
Augusto
, L. L. X.
, Lopes
, G. C.
, and Gonçalves
, J. A. S.
, “A CFD study of deposition of pharmaceutical aerosols under different respiratory conditions
,” Braz. J. Chem. Eng.
33
(3
), 549
–558
(2016
).4.
Balásházy
, I.
, Farkas
, A.
, Hofmann
, W.
, and Kurunczi
, S.
, “Local deposition distributions of inhaled radionuclides in the human tracheobronchial tree
,” Radiat. Prot. Dosim.
99
(1
), 469
–470
(2002
).5.
Borghardt
, J. M.
, Kloft
, C.
, and Sharma
, A.
, “Inhaled therapy in respiratory disease: The complex interplay of pulmonary kinetic processes
,” Can. Respir. J.
2018
, 2732017
.6.
Borojeni
, A. A. T.
, Noga
, M. L.
, Vehring
, R.
, and Finlay
, W. H.
, “Measurements of total aerosol deposition in intrathoracic conducting airway replicas of children
,” J. Aerosol Sci.
73
, 39
–47
(2014
).7.
Chakravarty
, A.
, Patankar
, N. A.
, and Panchagnula
, M. V.
, “Aerosol transport in a breathing alveolus
,” Phys. Fluids
31
, 121901
(2019
).8.
Chan
, T. L.
, and Lippmann
, M.
, “Experimental measurement and empirical modelling of the regional deposition of inhaled particles in humans
,” Am. Ind. Hyg. Assoc. J.
41
, 399
–409
(1980
).9.
Cheng
, Y. S.
, “Aerosol deposition in the extrathoracic region
,” Aerosol Sci. Technol.
37
(8
), 659
–671
(2003
).10.
Das
, P.
, Nof
, E.
, Amirav
, I.
, Kassinos
, S. C.
, and Sznitman
, J.
, “Targeting inhaled aerosol delivery to upper airways in children: Insight from computational fluid dynamics (CFD)
,” PLoS One
13
(11
), e0207711
(2018
).11.
Dal Negro
, R. W.
, “Dry powder inhalers and the right things to remember: A concept review
,” Multidiscip. Respir. Med.
10
(1
), 13
(2015
).12.
Dong
, J.
, Li
, J.
, Tian
, L.
, and Tu
, J.
, “Transport and deposition of ultrafine particles in the upper tracheobronchial tree: A comparative study between approximate and realistic respiratory tract models
,” Comput. Methods Biomech. Biomed. Eng.
(published online) (2021
).13.
Elcner
, J.
, Lizal
, F.
, Jedelsky
, J.
, Jicha
, M.
, and Chovancova
, M.
, “Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results
,” Biomech. Model. Mechanobiol.
15
, 447
–469
(2016
).14.
Faizal
, W. M.
, Ghazali
, N. N. N.
, Khor
, C. Y.
, Badruddin
, I. A.
, Zainon
, M. Z.
, Yazid
, A. A.
, Ibrahim
, N. B.
, and Razi
, R. M.
, “Computational fluid dynamics modelling of human upper airway: A review
,” Comput. Methods Programs Biomed.
196
, 105627
–105622
(2020
).15.
Farnoud
, A.
, Tofighian
, H.
, Baumann
, I.
, Garcia
, G. J. M.
, Schmid
, O.
, Gutheil
, E.
, and Rashidi
, M. M.
, “Large eddy simulations of airflow and particle deposition in pulsating bidirectional nasal drug delivery
,” Phys. Fluids
32
, 101905
(2020
).16.
Farkas
, A.
, Lizal
, F.
, Jedelsky
, J.
, Elcner
, J.
, Horváth
, A.
, and Jicha
, M.
, “Simulation of airway deposition of an aerosol drug in COPD patients
,” Pharmaceutics
11
(4
), 153
–162
(2019
).17.
Finlay
, W. H.
, The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction
(Academic Press
, London
, 2019
).18.
Inthavong
, K.
, Zhang
, K.
, and Tu
, J.
, “Numerical modelling of nanoparticle deposition in the nasal cavity and the tracheobronchial airway
,” Comput. Methods Biomech. Biomed. Eng.
14
(7
), 633
–643
(2011
).19.
Islam
, M. S.
, Larpruenrudee
, P.
, Paul
, A. R.
, Paul
, G.
, Gemci
, T.
, Gu
, Y. T.
, and Saha
, S. C.
, “SARS CoV-2 aerosol: How far it can travel to the lower airways?
,” Phys. Fluids
33
, 061903
(2021
).20.
Islam
, M. S.
, Paul
, G.
, Ong
, H. X.
, Young
, P. M.
, Gu
, Y. T.
, and Saha
, S. C.
, “A review of respiratory anatomical development, air flow characterization and particle deposition
,” Int. J. Environ. Res. Public Health
17
, 380
(2020
).21.
Islam
, M. S.
, Saha
, S. C.
, Gemci
, T.
, Yang
, I. A.
, Sauret
, E.
, Ristovski
, Z.
, and Gu
, Y. T.
, “Euler-Lagrange prediction of diesel-exhaust polydisperse particle transport and deposition in lung: Anatomy and turbulence effects
,” Sci. Rep.
9
, 12423
(2019a
).22.
Islam
, M. S.
, Saha
, S. C.
, Sauret
, E.
, Gu
, Y. T.
, and Ristovski
, Z. D.
, “Ultrafine particle transport and deposition in a large scale 17-generation lung model
,” J. Biomech.
64
, 16
–25
(2017
).23.
Islam
, M. S.
, Saha
, S. C.
, Sauret
, E.
, Ong
, H.
, Young
, P.
, and Gu
, Y. J. T. R.
, “Euler–Lagrange approach to investigate respiratory anatomical shape effects on aerosol particle transport and deposition
,” Toxicol. Res. Appl.
3
, 2397847319894675
(2019b
).24.
Jedelsky
, J.
, Lizal
, F.
, and Jicha
, M.
, “Characteristics of turbulent particle transport in human airways under steady and cyclic flows
,” Int. J. Heat Fluid Flow
35
, 84
–92
(2012
).25.
Kannan
, R. R.
, Przekwas
, A.
, Singh
, N.
, Delvadia
, R.
, Tian
, G.
, and Walenga
, R.
, “Pharmaceutical aerosols deposition patterns from a dry powder inhaler: Euler Lagrangian prediction and validation
,” Med. Eng. Phys.
42
, 35
–47
(2017
).26.
Karakosta
, P.
, Alexopoulos
, A. H.
, and Kiparissides
, C.
, “Computational model of particle deposition in the nasal cavity under steady and dynamic flow
,” Comput. Methods Biomech. Biomed. Eng.
18
, 514
–526
(2015
).27.
Khan
, I.
, Elhissi
, A.
, Shah
, M.
, Alhnan
, M. A.
, and Ahmed
, W.
, “Liposome-based carrier systems and devices used for pulmonary drug delivery
,” in Biomaterials and Medical Tribology
, Woodhead Publishing Series in Biomaterials, edited by J. P.
Davim
(Woodhead Publishing
, 2013
), Chap. 9, pp. 395
–443
.28.
Lambert
, A. R.
, O'Shaughnessy
, P.
, Tawhai
, M. H.
, Hofman
, E. A.
, and Lin
, C.
, “Regional deposition of particles in an image-based airway model: Large-eddy simulation and left-right lung ventilation asymmetry
,” Aerosol Sci. Technol.
45
, 11
–25
(2011
).29.
Laube
, B. L.
, and Dolovich
, M. B.
, “Aerosols and aerosol drug delivery systems
,” in Middleton's Allergy
, 8th ed., edited by N. F.
Adkinson
, B. S.
Bochner
, A. W.
Burks
, W. W.
Busse
, S. T.
Holgate
, R. F.
Lemanske
, and R. E.
O'Hehir
(W.B. Saunders
, 2014
), Chap. 66, pp. 1066
–1082
.30.
Lin
, C. L.
, Tawhai
, M. H.
, and Hoffman
, E. A.
, “Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs
,” Wiley Interdiscip. Rev.
5
, 643
–655
(2013
).31.
Lindert
, S.
, Below
, A.
, and Breitkreutz
, J.
, “Performance of dry powder inhalers with single dosed capsules in preschool children and adults using improved upper airway models
,” Pharmaceutics
6
, 36
–51
(2014
).32.
Liu
, Z.
, Li
, A.
, Xu
, X.
, and Rao
, R.
, “Computational fluid dynamics simulation of airflow patterns and particle deposition characteristics in children upper human respiratory tracts
,” Eng. Appl. Comput. Fluid Mech.
6
(4
), 556
–571
(2012
).33.
Lizal
, F.
, Elcner
, J.
, Jedelsky
, J.
, Maly
, M.
, Jicha
, M.
, Farkas
, Á.
, Belka
, M.
, Rehak
, Z.
, Adam
, J.
, Brinek
, A.
, Laznovsky
, J.
, Zikmund
, T.
, and Kaiser
, J.
, “The effect of oral and nasal breathing on the deposition of inhaled particles in upper and tracheobronchial airways
,” J. Aerosol Sci.
150
, 105649
(2020
).34.
Longest
, P. W.
, and Vinchurkar
, S.
, “Effects of mesh style and grid convergence on particle deposition in bifurcating airway models with comparisons to experimental data
,” Med. Eng. Phys.
29
(3
), 350
–366
(2007
).35.
Menter
F. R.
, “Two-equation eddy-viscosity turbulence models for engineering applications
,” AIAA J.
32
(8
), 1598
–1605
(1994
).36.
Morsi
, S.
, and Alexander
, A.
, “An investigation of particle trajectories in two-phase flow systems
,” J. Fluid Mech.
55
(2
), 193
–208
(1972
).37.
Newman
, S. P.
, “Aerosols
,” in Encyclopedia of Respiratory Medicine
, edited by G. J.
Laurent
and S. D.
Shapiro
(Academic Press
, 2006
), pp. 58
–64
.38.
Nordlund
, M.
, Belka
, M.
, Kuczaj
, A. K.
, Lizal
, F.
, Elcner
, J. J.
, Jicha
, M.
, Sauser
, Y.
, Le Bouhellec
, S.
, Cosandey
, S.
, Majeed
, S.
, Vuillaume
, G.
, Peitsch
, M. C.
, and Hoeng
, J.
, “Multi-component aerosol particle deposition in a realistic cast of the human upper respiratory tract
,” Inhalation Toxicol.
29
(3
), 113
–125
(2017
).39.
Nowak
, N.
, Kakade
, P. P.
, and Annapragada
, A. V.
, “Computational fluid dynamics simulation of airflow and aerosol deposition in human lungs
,” Ann. Biomed. Eng.
31
, 374
–390
(2003
).40.
Rahimi-Gorji
, M.
, Pourmehran
, O.
, Gorji-Bandpy
, M.
, and Gorji
, T. B.
, “CFD simulation of airflow behavior and particle transport and deposition in different inhalation conditions through the realistic model of human airways
,” J. Mol. Liq.
209
, 121
–133
(2015
).41.
Sallam
, A. A. N.
, “Quality by design considerations for product development of dry-powder inhalers
,” in Pharmaceutical Quality by Design: Principles and Applications
, edited by S.
Beg
and M. S.
Hasnain
(Academic Press
, 2019
), Chap. 9, pp. 173
–192
.42.
Sera
, T.
, Uesugi
, K.
, Yagi
, N.
, and Yokota
, H.
, “Numerical simulation of airflow and microparticle deposition in a synchrotron micro-CT-based pulmonary acinus model
,” Comput. Methods Biomech. Biomed. Eng.
18
, 1427
–1435
(2015
).43.
Shachar-Berman
, L.
, Bhardwaj
, S.
, Ostrovski
, Y.
, Das
, P.
, Koullapis
, P.
, Kassinos
, S.
, and Sznitman
, J.
, “In silico optimization of fiber-shaped aerosols in inhalation therapy for augmented targeting and deposition across the respiratory tract
,” Pharmaceutics
12
(3
), 230
(2020
).44.
Srivastav
, V. K.
, Jain
, A.
, Paul
, A. R.
, and Joshi
, S.
, “CFD modelling of airflow in human respiratory system
,” in Proceedings of the 9th International Conference on Mechanical Engineering (ICME-2011)
, Dhaka, Bangladesh, 18–20 December (2011a
).45.
Srivastav
, V. K.
, Kumar
, A.
, Shukla
, S. K.
, Paul
, A. R.
, Bhatt
, A. D.
, and Jain
, A.
, “Airflow and aerosol-drug delivery in a CT scan based human respiratory tract with tumor using CFD
,” J. Appl. Fluid Mech.
7
(2
), 345
–356
(2014
).47.
Srivastav
, V. K.
, Paul
, A. R.
, and Jain
, A.
, “Computational fluid dynamics study of airflow and particle transport in third to sixth generation human respiratory tract
,” Int. J. Emerging Multidiscip. Fluid Sci.
3
(4
), 227
(2011b
).48.
Srivastav
, V. K.
, Paul
, A. R.
, and Jain
, A.
, “Effects of cartilaginous rings on airflow and particle transport through simplified and realistic models of human upper respiratory tracts
,” Acta Mech. Sin.
29
(6
), 883
–892
(2013
).46.
Srivastav
, V. K.
, Paul
, A. R.
, and Jain
, A.
, “Capturing the wall turbulence in CFD simulation of the human respiratory tract
,” Math. Comput. Simul.
160
(C
), 23
–38
(2019
).49.
Telko
, M. J.
, and Hickey
, A. J.
, “Dry powder inhaler formulation
,” Respir. Care
50
(9
), 1209
–1227
(2005
).50.
Tong
, Z.
, Yu
, A.
, Chan
, H. K.
, and Yang
, R.
, “Discrete modelling of powder dispersion in dry powder inhalers: A brief review
,” Curr. Pharm. Des.
21
(27
), 3966
–3973
(2015
).51.
Zhang
, Z.
, Kleinstreuer
, C.
, and Kim
, C. S.
, “Computational analysis of micron-particle deposition in a human triple bifurcation airway model
,” Comput. Methods Biomech. Biomed. Eng.
5
, 135
–147
(2002b
).52.
Zhang
Z.
, Kleinstreuer
C.
, and Kim
C. S.
, “Micro-particle transport and deposition in a human oral airway model
,” J. Aerosol Sci.
33
, 1635
–1652
(2002a
).© 2021 Author(s). Published under an exclusive license by AIP Publishing.
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