The use of extrathoracic airway replicas in optimization of drug delivery to the lungs with nebulizers, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) is discussed. Such airway replicas have been useful in evaluating new pulmonary drug delivery platforms mainly based on the comparison of the total lung dose (TLD) and the aerodynamic particle size distribution (APSD) of the aerosol distal to the physical models. The ability of these in vitro methods to replicate in vivo results has allowed advancements in respiratory drug delivery and in the accuracy and utility of in vitro-in vivo correlations (IVIVCs).
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References
1.
ByronPR, HindleM, LangeCF, LongestPW, McRobbieD, OldhamMJ, OlssonB, ThielCG, WachtelH, and FinlayWH: In vivo-in vitro correlations: Predicting pulmonary drug deposition from pharmaceutical aerosols. J Aerosol Med Pulm Drug Deliv. 2010; 23Suppl 2:S59–S69.
2.
FinlayWH, and MartinAR: Recent advances in predictive understanding of respiratory tract deposition. J Aerosol Med. 2008; 21:189–206.
3.
ZhouY, SunJ, and ChengY-S: Comparison of deposition in the USP and physical mouth-throat models with solid and liquid particles. J Aerosol Med Pulm Drug Deliv. 2011; 24:277–284.
4.
DelvadiaRR, LongestPW, and ByronPR: In vitro tests for aerosol deposition. I: Scaling a physical model of the upper airways to predict drug deposition variation in normal humans. J Aerosol Med Pulm Drug Deliv. 2012; 25:32–40.
5.
GolshahiL, and FinlayWH: An idealized child throat that mimics average pediatric oropharyngeal deposition. Aerosol Sci Technol. 2012; 46:i–iv.
6.
JavaheriE, GolshahiL, and FinlayWH: An idealized geometry that mimics average infant nasal airway deposition. J Aerosol Sci. 2013; 55:137–148.
7.
WachtelH, BickmannD, BreitkreutzJ, and LangguthP: Can pediatric throat models and air flow profiles improve our dose finding strategy?. Respir Drug Deliv. 2010; 1:195–204.
8.
OlssonB, BorgströmL, LundbäckH, and SvenssonM: Validation of a general in vitro approach for prediction of total lung deposition in healthy adults for pharmaceutical inhalation products. J Aerosol Med Pulm Drug Deliv. 2013; 26:355–69.
9.
Aerosols, NasalSprays, Metered DoseInhalers, and Dry PowderInhalers. The United States Pharmacopeia—National Formulary. United States Pharmacopeial, 2009.
10.
StapletonKW, GucntschE, HoskinsonMK, and FinlayWH: On the suitability of κ-ɛ turbulence modeling for aerosol deposition in the mouth and throat: A comparison with experiment. J Aerosol Sci. 2000; 31:739–749.
11.
BurnellPKP, AskingL, BorgströmL, NicholsSC, OlssonB, PrimeD, and ShrubbI: Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV—the oropharyngeal retention effect for four inhalation delivery systems. J Aerosol Med. 2007; 20:269–81.
12.
McRobbieDW, and PritchardSE: Studies of the human oropharyngeal airspaces using magnetic resonance imaging. III. The effects of device resistance with forced maneuver and tidal breathing on upper airway geometry. J Aerosol Med. 2005; 18:325–336.
13.
GrgicB, FinlayW, BurnellPK, and HeenanA: In vitro intersubject and intrasubject deposition measurements in realistic mouth–throat geometries. J Aerosol Sci. 2004; 35:1025–1040.
14.
XiJ, and LongestPW: Transport and deposition of micro-aerosols in realistic and simplified models of the oral airway. Ann Biomed Eng. 2007; 35:560–581.
15.
EhtezaziT, SouthernKW, AllansonD, JenkinsonI, and O'CallaghanC: Suitability of the upper airway models obtained from MRI studies in simulating drug lung deposition from inhalers. Pharm Res. 2005; 22:166–170.
16.
LongestPW, HindleM, Das ChoudhuriS, and XiJ: Comparison of ambient and spray aerosol deposition in a standard induction port and more realistic mouth–throat geometry. J Aerosol Sci. 2008; 39:572–591.
17.
JanssensHM, de JongsteJC, FokkensWJ, RobbenSG, WoutersK, and TiddensHA: The Sophia anatomical infant nose-throat (saint) model: A valuable tool to study aerosol deposition in infants. J Aerosol Med. 2001; 14:433–441.
18.
MitchellJP: Appropriate face models for evaluating drug delivery in the laboratory: The current situation and prospects for future advances. J Aerosol Med Pulm Drug Deliv. 2008; 21:97–112.
19.
MinocchieriS, BurrenJM, BachmannMA, SternG, WildhaberJ, BuobS, SchindelR, KraemerR, FreyUP, and NelleM: Development of the premature infant nose throat-model (PrINT-Model): An upper airway replica of a premature neonate for the study of aerosol delivery. Pediatr Res. 2008; 64:141–146.
20.
LaubeBL, SharplessG, ShermerC, NasirO, SullivanV, and PowellK: Deposition of albuterol aerosol generated by pneumatic nebulizer in the Sophia anatomical infant nose-throat (SAINT) model. Pharm Res. 2010; 27:1722–1729.
21.
SchüeppKG, JauernigJ, JanssensHM, TiddensHAWM, StraubDA, StanglR, KellerM, and WildhaberJH: In vitro determination of the optimal particle size for nebulized aerosol delivery to infants. J Aerosol Med. 2005; 18:225–235.
22.
TiemersmaS, MinocchieriS, van LingenRA, NelleM, and DevadasonSG: Vibrating membrane devices deliver aerosols more efficient than standard devices: A study in a neonatal upper airway model. J Aerosol Med Pulm Drug Deliv. 2013; 26:280–286.
23.
SmaldoneGC, BergE, and NikanderK: Variation in pediatric aerosol delivery: Importance of facemask. J Aerosol Med. 2005; 18:354–363.
24.
LoucaE, LeungK, CoatesAL, MitchellJP, and NagelMW: Comparison of three valved holding chambers for the delivery of fluticasone propionate-HFA to an infant face model. J Aerosol Med. 2006; 19:160–167.
25.
GolshahiL, TelidetzkiK, KingB, ShawD, and FinlayWH: A pilot study on the use of geometrically accurate face models to replicate ex vivo N95 mask fit. Am J Infect Control. 2013; 41:77–79.
26.
CarrigyNB, O'ReillyC, SchmittJ, NogaM, and FinlayWH: Effect of facial material softness and applied force on face mask dead volume, face mask seal, and inhaled corticosteroid delivery through an idealized infant replica. J Aerosol Med Pulm Drug Deliv. 2014; 27:290–298.
27.
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.
28.
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.
29.
EhtezaziT, HorsfieldMA, BarryPW, and O'CallaghanC: Dynamic change of the upper airway during inhalation via aerosol delivery devices. J Aerosol Med. 2004; 17:325–334.
30.
CorcoranTE, ShortallBP, KimIK, MezaMP, and ChigierN: Aerosol drug delivery using heliox and nebulizer reservoirs: Results from an MRI-based pediatric model. J Aerosol Med. 2003; 16:263–271.
31.
BickmannD, WachtelH, KroegerR, and LangguthP. Examining inhaler performance using a child's throat model. Respir Drug Deliv 2008. 2008; 2:565–70.
32.
BelowA, BickmannD, and BreitkreutzJ: Assessing the performance of two dry powder inhalers in preschool children using an idealized pediatric upper airway model. Int J Pharm. 2013; 444:169–174.
33.
FinlayWH, RuzyckiCA, GolshahiL, and VehringR: Validating and scaling the Alberta Idealized Child Throat. Respir Drug Deliv 2014. 2014; 1:303–310.
34.
LongestPW, and HindleM: Evaluation of the Respimat Soft Mist Inhaler using a concurrent CFD and in vitro approach. J Aerosol Med Pulm Drug Deliv. 2009; 22:99–112.
35.
AmiravI, BorojeniAAT, HalamishA, NewhouseMT, and GolshahiL: Nasal versus oral aerosol delivery to the “lungs” in infants and toddlers. Pediatr Pulmonol. 2014; 50:276–283.
36.
ChengYS: Aerosol deposition in the extrathoracic region. Aerosol Sci Technol. 2003; 37:659–671.
37.
CarrigyNB, RuzyckiCA, GolshahiL, and FinlayWH: Pediatric in vitro and in silico models of deposition via oral and nasal inhalation. J Aerosol Med Pulm Drug Deliv. 2014; 27:149–169.
38.
OlssonB: Aerosol particle generation from dry powder inhalers: Can they equal pressurized metered dose inhalers?. J Aerosol Med. 1995; 8Suppl 3:S13–8; discussion S19.
39.
SrichanaT, MartinGP, and MarriottC: A human oral-throat cast integrated with a twin-stage impinger for evaluation of dry powder inhalers. J Pharm Pharmacol. 2000; 52:771–778.
40.
OlssonB, BorgstromL, AskingL, and BondessonE: Effect of inlet throat on the correlation between measured fine particle dose and lung deposition. Respir Drug Deliv V. 1996; 1:273–82.
41.
VelasquezDJ, and GabrioB: Metered dose inhaler aerosol deposition in a model of the human respiratory system and a comparison with clinical deposition studies. J Aerosol Med. 1998; 11Suppl 1:S23–S28.
42.
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.
43.
FadlA, WangJ, YangP, ZhangZ, and ChengYS: Balloon-based in vitro MDI aerosol deposition experiments on the effects of mouthpiece diameter. Inhal Toxicol. 2007; 19:505–515.
44.
FadlA, WangJ, ZhangZ, and Sung ChengY: Effects of MDI spray angle on aerosol penetration efficiency through an oral airway cast. J Aerosol Sci. 2007; 38:853–864.
45.
DelvadiaRR, LongestPW, HindleM, and ByronPR: In vitro tests for aerosol deposition. III: Effect of inhaler insertion angle on aerosol deposition. J Aerosol Med Pulm Drug Deliv. 2013; 26:145–156.
46.
TianG, LongestPW, SuG, WalengaRL, and HindleM: Development of a stochastic individual path (SIP) model for predicting the tracheobronchial deposition of pharmaceutical aerosols: Effects of transient inhalation and sampling the airways. J Aerosol Sci. 2011; 42:781–99.
47.
ByronP., DelvadiaRR, LongestPW, and HindleM: Stepping into the trachea with realistic physical models: Uncertainties in regional drug deposition from powder inhalers. Respir Drug Deliv 2010. 2010; 1:215–24.
48.
YehH-C, and SchumGM: Models of human lung airways and their application to inhaled particle deposition. Bull Math Biol. 1980; 42:461–480.
49.
NewmanSP, PitcairnGR, HirstPH, BaconRE, O'KeefeE, ReinersM, and HermannR: Scintigraphic comparison of budesonide deposition from two dry powder inhalers. Eur Respir J. 2000; 16:178–183.
50.
DelvadiaR, HindleM, LongestPW, and ByronPR: In vitro tests for aerosol deposition II: IVIVCs for different dry powder inhalers in normal adults. J Aerosol Med Pulm Drug Deliv. 2013; 26:138–144.
51.
LongestPW, TianG, WalengaRL, and HindleM: Comparing MDI and DPI aerosol deposition using in vitro experiments and a new stochastic individual path (SIP) model of the conducting airways. Pharm Res. 2012; 29:1670–1688.
52.
PowellKG, ChanL, ShermerCD, and KrayerJD: Environmental effects on the performance of a novel disposable pulmonary delivery device. Respir Drug Deliv 2008. 2008; 2:399–404.
53.
ChanL, ShermerCD, PowellKG, and KrayerJD: Spacer considerations in pulmonary delivery to young children. Respir Drug Deliv 2008. 2008; 2:395–398.
54.
LaubeBL, SharplessG, ShermerC, SullivanV, and PowellK: Deposition of dry powder generated by solovent in Sophia Anatomical Infant Nose-Throat (SAINT) model. Aerosol Sci Technol. 2012; 46:514–520.
55.
JanssensHM, De JongsteJC, HopWCJ, and TiddensHAWM: Extra-fine particles improve lung delivery of inhaled steroids in infants: A study in an upper airway model. Chest. 2003; 123:2083–2088.
56.
JanssensHM, KrijgsmanA, VerbraakTFM, HopWCJ, de JongsteJC, and TiddensHAWM: Determining factors of aerosol deposition for four pMDI-spacer combinations in an infant upper airway model. J Aerosol Med. 2004; 17:51–61.
57.
BorgströmL, OlssonB, and ThorssonL: Degree of throat deposition can explain the variability in lung deposition of inhaled drugs. J Aerosol Med. 2006; 19:473–483.
58.
RuzyckiCA, GolshahiL, VehringR, and FinlayWH: Comparison of in vitro deposition of pharmaceutical aerosols in an idealized child throat with in vivo deposition in the upper respiratory tract of children. Pharm Res. 2014; 31:1525–1535.
59.
AzhdarzadehM, OlfertJS, VehringR, and FinlayWH: Effect of electrostatic charge on oral-extrathoracic deposition for uniformly charged monodisperse aerosols. J Aerosol Sci. 2014; 68:38–45.
60.
AzhdarzadehM, OlfertJS, VehringR, and FinlayWH: Effect of induced charge on deposition of uniformly charged particles in a pediatric oral-extrathoracic airway. Aerosol Sci Technol. 2014; 48:508–514.
61.
AzhdarzadehM, OlfertJS, VehringR, and FinlayWH: Effect of electrostatic charge on deposition of uniformly charged monodisperse particles in the nasal extrathoracic airways of an infant. J Aerosol Med Pulm Drug Deliv. 2015; 28:30–34.
