A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery.
Methods:
An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device. Inhalation flow rates of 15, 30, and 60 L/min were used and drug particle tracking was a one-way coupled Lagrangian model.
Results:
The results showed that most particles deposited in the pharynx, where the airway has a reduced cross-sectional area. Particle deposition generally decreased with initial spray velocity and with increased spray cone angle for 30 and 60 L/min flow rates. However, for 15 L/min flow rate, the deposition increased slightly with an increase in the spray velocity and cone angle. The effect of spray cone angle was more significant than the initial spray velocity on particle deposition. When the MMAD of a PSD was reduced, the deposition efficiency also reduces, suggesting greater rates of particle entry into the lung. The deposition rate showed negligible change when the MMAD was more than 8 μm.
Conclusion:
Spray injection angle and velocity change the drug delivery efficacy; however, the efficiency shows more sensitivity to the injection angle. The 30 L/min airflow rate delivers spray particles to the lung more efficiently than 15 and 60 L/min airflow rate, and reducing MMAD can help increase drug delivery to the lung.
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References
1.
DarquenneC: Aerosol deposition in health and disease. J Aerosol Med Pulm Drug Deliv. 2012; 25:140–147.
2.
YangMY, ChanJG, and ChanHK: Pulmonary drug delivery by powder aerosols. J Control Release. 2014; 193:228–240.
3.
ZhouQT, TangP, LeungSS, ChanJG, and ChanHK: Emerging inhalation aerosol devices and strategies: Where are we headed?. Adv Drug Deliv Rev. 2014; 75:3–17.
4.
DolovichMB, AhrensRC, HessDR, AndersonP, DhandR, RauJL, SmaldoneGC, and GuyattG; American College of Chest P, American College of Asthma A, and Immunology. Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005; 127:335–371.
5.
HaughneyJ, PriceD, BarnesNC, VirchowJC, RocheN, and ChrystynH: Choosing inhaler devices for people with asthma: Current knowledge and outstanding research needs. Respir Med. 2010; 104:1237–1245.
6.
RossDL, and GabrioBJ: Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system. J Aerosol Med. 1999; 12:151–160.
7.
O'ConnorBJ: The ideal inhaler: Design and characteristics to improve outcomes. Respir Med. 2004; 98Suppl A:S10–S16.
8.
LavoriniF, CorriganCJ, BarnesPJ, DekhuijzenPRN, LevyML, PedersenS, RocheN, VinckenW, and CromptonGK: Retail sales of inhalation devices in European countries: So much for a global policy. Respir Med. 2011; 105:1099–1103.
9.
NewmanSP: Principles of metered-dose inhaler design. Respir Care. 2005; 50:1177–1190.
10.
DeHaanWH, and FinlayWH: In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices. J Aerosol Med. 2001; 14:361–367.
11.
KhilnaniG, and BangaA: Aerosol therapy. J Indian Assoc Clin Med. 2004; 5:114–123.
12.
ChengYS, FuCS, YazzieD, and ZhouY: Respiratory Deposition Patterns of Salbutamol pMDI with CFC and HFA-134a Formulations in a Human Airway Replica. J Aerosol Med. 2001; 14:255–266.
13.
SmithIJ, BellJ, BowmanN, EverardM, SteinS, and WeersJG: Inhaler devices: What remains to be done?. J Aerosol Med Pulm Drug Deliv. 2010; 23Suppl 2:S25–S37.
14.
YazdaniA, NormandieM, YousefiM, SaidiMS, and AhmadiG: Transport and deposition of pharmaceutical particles in three commercial spacer-MDI combinations. Comput Biol Med. 2014; 54:145–155.
15.
SteinSW, and MyrdalPB: A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J Pharm Sci. 2004; 93:2158–2175.
16.
VersteegHK, HargraveG, HarringtonL, ShrubbI, and HodsonD: The use of computational fluid dynamics (CFD) to predict pMD air flows and aerosol plume formation. In: DalbyRN, ByronPR, FarrsJ, and PeartJ (eds). Respiratory Drug Delivery VII. Raleigh Serentec Press, Inc., Raleigh, NC, USA, pp. 257–264, 2000.
17.
HochrainerD, HolzH, KreherC, ScaffidiL, SpallekM, and WachtelH: Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers. J Aerosol Med. 2005; 18:273–282.
18.
SmythH, BraceG, BarbourT, GallionJ, GroveJ, and HickeyAJ: Spray pattern analysis for metered dose inhalers: Effect of actuator design. Pharm Res. 2006; 23:1591–1596.
19.
KleinstreuerC, ShiH, and ZhangZ: Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology. J Aerosol Med. 2007; 20:294–309.
20.
DunbarC, and MillerJ: Theoretical investigation of the spray from a pressurized metered-dose inhaler. Atomization Sprays. 1997; 7. pp. 417–436.
21.
DunbarCA, WatkinsAP, and MillerJF: An Experimental Investigation of the Spray Issued from a pMDI Using Laser Diagnostic Techniques. J Aerosol Med. 1997; 10:351–368.
22.
BrambillaG, ChurchT, LewisD, and MeakinB: Plume temperature emitted from metered dose inhalers. Int J Pharm. 2011; 405:9–15.
23.
TamuraG: Comparison of the aerosol velocity of Respimat® soft mist inhaler and seven pressurized metered dose inhalers. Allergol Int. 2015; 64:390–392.
24.
OliveiraRF, FerreiraAC, TeixeiraSF, TeixeiraJC, and MarquesHC: pMDI Spray Plume Analysis: A CFD Study. Proceedings of the World Congress on Engineering. London, United Kingdom, Vol. 3, 2013.
25.
OliveiraRF, TeixeiraSF, TeixeiraJC, SilvaLF, and AntunesH: pMDI Sprays: Theory, experiment and numerical simulation. In: LiuC, (ed). Advances in Modeling of Fluid Dynamics. INTECH; 2012. Casablanca, Morocco.
26.
CroslandBM, JohnsonMR, and MatidaEA: Characterization of the spray velocities from a pressurized metered-dose inhaler. J Aerosol Med Pulm Drug Deliv. 2009; 22:85–98.
27.
ChengKH, ChengYS, YehHC, and SwiftDL: Measurements of airway dimensions and calculation of mass transfer characteristics of the human oral passage. J Biomech Eng. 1997; 119:476–482.
28.
KleinstreuerC, ZhangZ, and LiZ: Modeling airflow and particle transport/deposition in pulmonary airways. Respir Physiol Neurobiol. 2008; 163:128–138.
29.
LiZ, KleinstreuerC, and ZhangZ: Particle deposition in the human tracheobronchial airways due to transient inspiratory flow patterns. J Aerosol Sci. 2007; 38:625–644.
30.
ZhangZ, KleinstreuerC, DonohueJF, and KimCS: Comparison of micro- and nano-size particle depositions in a human upper airway model. J Aerosol Sci. 2005; 36:211–233.
31.
ZhangZ, and KleinstreuerC: Airflow structures and nano-particle deposition in a human upper airway model. J Comput Phys. 2004; 198:178–210.
32.
ZhangZ, KleinstreuerC, and KimCS: Micro-particle transport and deposition in a human oral airway model. J Aerosol Sci. 2002; 33:1635–1652.
33.
ZhangZ, and KleinstreuerC: Transient airflow structures and particle transport in a sequentially branching lung airway model. Phys Fluids. 2002; 14:862–880.
34.
YousefiM, InthavongK, and TuJ: Microparticle transport and deposition in the human oral airway: Toward the smart spacer. Aerosol Sci Technol. 2015; 49:1109–1120.
35.
StapletonK-W, GuentschE, HoskinsonM, and FinlayW: On the suitability of k–ɛ turbulence modeling for aerosol deposition in the mouth and throat: A comparison with experiment. J Aerosol Sci. 2000; 31:739–749.
36.
JohnstoneA, UddinM, PollardA, HeenanA, and FinlayWH: The flow inside an idealised form of the human extra-thoracic airway. Exp Fluids. 2004; 37:673–689.
37.
KleinstreuerC, and ZhangZ: Laminar-to-turbulent fluid-particle flows in a human airway model. Int J Multiph Flow. 2003; 29:271–289.
38.
InthavongK, ChoiL-T, TuJ, DingS, and ThienF: Micron particle deposition in a tracheobronchial airway model under different breathing conditions. Med Eng Phys. 2010; 32:1198–1212.
39.
Worth LongestP, and VinchurkarS: Validating CFD predictions of respiratory aerosol deposition: Effects of upstream transition and turbulence. J Biomech. 2007; 40:305–316.
40.
LongestPW, and XiJ: Effectiveness of direct lagrangian tracking models for simulating nanoparticle deposition in the upper airways. Aerosol Sci Technol. 2007; 41:380–397.
41.
WilcoxDC: Turbulence Modeling for CFD. DCW Industries, Incorporated; 1998.
42.
KralLD: Recent experience with different turbulence models applied to the calculation of flow over aircraft components. Prog Aerosp Sci. 1998; 34:481–541.
43.
KleinstreuerC: Two-Phase Flow: Theory and Applications. CRC Press; 2003.
44.
InthavongK, YeY, DingS, and TuJ: Comparative study of the effects of acute asthma in reltion to a recovered airway tree on airflow patterns. In: 13th International Conference on Biomedical Engineering. Springer, Singapore. pp. 1555–1558, 2009.
45.
MorsiS, and AlexanderA: An investigation of particle trajectories in two-phase flow systems. J Fluid Mech. 1972; 55:193–208.
46.
KallioGA, and ReeksMW: A numerical simulation of particle deposition in turbulent boundary layers. Int J Multiph Flow. 1989; 15:433–446.
47.
WangY, and JamesPW: On the effect of anisotropy on the turbulent dispersion and deposition of small particles. Int J Multiph Flow. 1999; 25:551–558.
48.
InthavongK, TianZF, LiHF, TuJY, YangW, XueCL, and LiCG: A numerical study of spray particle deposition in a human nasal cavity. Aerosol Sci Technol. 2006; 40:1034–1045.
49.
InthavongK, TuJ, and HeschlC: Micron particle deposition in the nasal cavity using the v2–f model. Comput Fluids. 2011; 51:184–188.
50.
MatidaEA, FinlayWH, LangeCF, and GrgicB: Improved numerical simulation for aerosol deposition in an idealized mouth-throat. J Aerosol Sci. 2004; 35:1–19.
51.
InthavongK, ZhangK, and TuJY: Modelling submicron and micron particle deposition in a human nasal cavity. In: SchwarzP, and WittP, (eds). Seventh International Conference on Computational Fluid Dynamics in the Minerals and Process Industries. CSIRO Minerals, Australia, Melbourne, Australia; 2009.
52.
InthavongK, ZhangK, and TuJ: Numerical modelling of nanoparticle deposition in the nasal cavity and the tracheobronchial airway. Comput Methods Biomech Biomed Eng. 2011; 14:633–643.
53.
DunbarCA, and HickeyAJ: Evaluation of probability density functions to approximate particle size distributions of representative pharmaceutical aerosols. J Aerosol Sci. 2000; 31:813–831.
54.
LinCL, TawhaiMH, McLennanG, and HoffmanEA: Characteristics of the turbulent laryngeal jet and its effect on airflow in the human intra-thoracic airways. Respir Physiol Neurobiol. 2007; 157:295–309.
55.
ChengY-S, ZhouY, and ChenBT: Particle deposition in a cast of human oral airways. Aerosol Sci Technol. 1999; 31:286–300.
56.
ZhouY, SunJ, and ChengYS: Comparison of deposition in the USP and physical mouth-throat models with solid and liquid particles. J Aerosol Med Pulm Drug Deliv. 2011; 24:8.
57.
ShiH, KleinstreuerC, and ZhangZ: Modeling of inertial particle transport and deposition in human nasal cavities with wall roughness. J Aerosol Sci. 2007; 38:398–419.
58.
LambertAR, O'ShaughnessyPT, TawhaiMH, HoffmanEA, and LinC-L: Regional deposition of particles in an image-based airway model: large-eddy simulation and left-right lung ventilation asymmetry. Aerosol Sci Technol. 2011; 45:11–25.
59.
RauJL: Determinants of patient adherence to an aerosol regimen. Respir Care. 2005; 50:1346–1356; discussion 1357–1349.
60.
OliveiraRF, FerreiraAC, TeixeiraSF, TeixeiraJC, and MarquesHC: pMDI Spray Plume Analysis: A CFD Study. In: Proceedings of the World Congress on Engineering. Vol. 3, 2013. London, UK.
61.
LewisDA: Intrinsic particle size distribution: A new metric to guide the design of HFA solution pMDIs. RRD Eur. 2013; 2013:175–184.
62.
XiJ, and LongestPW: Transport and deposition of microaerosols in realistic and simplified models of the oral airway. Ann Biomed Eng. 2007; 35:560–581.
63.
ZhangY, GilbertsonK, and FinlayWH: In vivo-in vitro comparison of deposition in three mouth-throat models with Qvar® and Turbuhaler® inhalers. J Aerosol Med. 2007; 20:227–235.
64.
LeachCL, DavidsonPJ, HasselquistBE, and BoudreauRJ: Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler. J Aerosol Med. 2005; 18:379–385.
65.
OliveiraRF, FerreiraAC, TeixeiraSF, TeixeiraJC, and Cabral-MarquesH: A CFD study of a pMDI plume spray. In: KimHK, AmouzegarMA, and AoSI (eds). Transactions on Engineering Technologies. Springer, Heidelberg. pp. 163–176, 2014.
66.
KwokPC, GloverW, and ChanHK: Electrostatic charge characteristics of aerosols produced from metered dose inhalers. J Pharm Sci. 2005; 94:2789–2799.
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