Targeting aerosol deposition to and within the lung airways using excipient enhanced growth

Journal of Aerosol Medicine and Pulmonary Drug Delivery

Volumn 26, Issue 5, 2013, Pages 248-265

  Tian, Geng ^a   Longest, P Worth ^a   Li, Xiang ^a   Hindle, Michael ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

computational fluid dynamics (CFD) simulations; engineered combination particles; excipient enhanced growth (EEG); hygroscopic droplet growth; in vitro aerosol experiments; nanoaerosols; respiratory drug delivery; stochastic individual path (SIP) airway modeling

Indexed keywords

EXCIPIENT; INSULIN; MANNITOL; SALBUTAMOL SULFATE; SODIUM CHLORIDE;

AEROSOL; ARTICLE; COMPUTATIONAL FLUID DYNAMICS; DRUG DELIVERY SYSTEM; DRY POWDER INHALER; FLOW RATE; GEOMETRY; MOUTH; PARTICLE SIZE; PREDICTION; SIMULATION; THROAT; TRACHEOBRONCHIAL TREE;

ADMINISTRATION, INHALATION; AEROSOLS; ALBUTEROL; DRUG DELIVERY SYSTEMS; EXCIPIENTS; HYDRODYNAMICS; HYGROSCOPIC AGENTS; INSULIN; LUNG; MANNITOL; MODELS, THEORETICAL; NEBULIZERS AND VAPORIZERS; PARTICLE SIZE; RESPIRATORY SYSTEM; SODIUM CHLORIDE; SOLUBILITY; THERMODYNAMICS; TISSUE DISTRIBUTION;

EID: 84878529022     PISSN: 19412711     EISSN: 19412703     Source Type: Journal    
DOI: 10.1089/jamp.2012.0997     Document Type: Article

References (81)

1. Byron PR: Drug delivery devices: issues in drug development. Proc Am Thorac Soc. 2004;1:321-328.
2. Smaldone GC: Advances in aerosols: adult respiratory disease. J Aerosol Med. 2006;19:36-46.
3. Smith IJ, Bell J, Bowman N, Everard M, Stein S, and Weers JG: Inhaler devices: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23:S25-S37.
4. Weers JG, Bell J, Chan HK, Cipolla D, Dunbar C, Hickey AJ, and Smith IJ: Pulmonary formulations: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23:S5-S23.
5. Borgstrom L, Olsson B, and Thorsson L: Degree of throat deposition can explain the variability in lung deposition of inhaled drugs. J Aerosol Med. 2006;19:473-483. (Pubitemid 46067766)
6. Hirst PH, Bacon RE, Pitcairn GR, Silvasti M, and Newman SP: A comparison of the lung deposition of budesonide from Easyhaler-, Turbuhaler-and pMDI plus spacer in asthmatic patients. Respir Med. 2001;95:720-727.
7. Newman SP, and Busse WW: Evolution of dry powder inhaler design, formulation, and performance. Respir Med. 2002;96:293-304.
8. Cheng YS, Fu CS, Yazzie D, and Zhou Y: Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica. J Aerosol Med. 2001;14:255-266. (Pubitemid 32744357)
9. Leach CL, Davidson PJ, and Bouhuys A: Improved airway targeting with the CFC-free HFA-beclomethasone metereddose inhaler compared with CFC-beclomethasone. Eur Respir J. 1998;12:1346-1353. (Pubitemid 29011427)
10. Longest PW, Tian G, Walenga RL, and Hindle M: 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.
11. Delvadia R, Longest PW, and Byron PR: 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.
12. Dunbar CA, Watkins AP, and Miller JF: An experimental investigation of the spray issued from a pMDI using laser diagnostic techniques. J Aerosol Med. 1997;10:351-368. (Pubitemid 28006475)
13. Newman S, Salmon A, Nave R, and Drollmann A: High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med. 2006;100: 375-384. (Pubitemid 43239871)
14. Zhang Y, Gilbertson K, and Finlay WH: In vivo-in vitro comparison of deposition in three mouth-throat models with Qvar and Turbuhaler inhalers. J Aerosol Med. 2007; 20:227-235. (Pubitemid 47463180)
15. Hochrainer D, Holz H, Kreher C, Scaffidi L, Spallek M, and Wachtel H: 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. (Pubitemid 41395729)
16. Newman SP, Brown J, Steed KP, Reader SJ, and Kladders H: Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices. Chest. 1998;113:957-963. (Pubitemid 28216438)
17. Pitcairn G, Reader S, Pavia D, and Newman S: Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist Inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry power inhaler. J Aerosol Med. 2005;18:264-272. (Pubitemid 41395728)
18. Nikander K, Prince I, Coughlin S, Warren S, and Taylor G: Mode of breathing-tidal or slow and deep-through the Ineb adaptive delivery (ADD) system affects lung deposition of 99mTc-DTPA. J Aerosol Med Pulm Drug Deliv. 2010;23(S1): S37-S43.
19. Zeman KL, Wu J, and Bennett WD: Targeting aerosolized drugs to the conducting airways using very large particles and extremely slow inhalations. J Aerosol Med Pulm Drug Deliv. 2010;23:363-369.
20. Longest PW, Hindle M, and Das Choudhuri S: Effects of generation time on spray aerosol transport and deposition in models of the mouth-throat geometry. J Aerosol Med Pulm Drug Deliv. 2009;22:67-84.
21. Geller DE, Weers J, and Heuerding S: Development of an inhaled dry-powder formulation of Tobramycin using PulmoSphere-technology. J Aerosol Med Pulm Drug Deliv. 2011;24:175-182.
22. Dinh KV, Myers DJ, Noymer PD, and Cassella JV: In vitro aerosol deposition in the oropharyngeal region for Staccato-loxapine. J Aerosol Med Pulm Drug Deliv. 2010;23:253-260.
23. Kim CS, and Jaques PA: Respiratory dose of inhaled ultrafine particles in healthy adults. Philos Trans R Soc Lond A. 2000;358:2693-2705.
24. Hindle M, and Longest PW: Condensational growth of combination drug-excipient submicrometer particles for targeted high efficiency pulmonary delivery: evaluation of formulation and delivery device. J Pharm Pharmacol. 2012; 64:1254-1263.
25. Hindle M, and Longest PW: Evaluation of enhanced condensational growth (ECG) for controlled respiratory drug delivery in a mouth-throat and upper tracheobronchial model. Pharm Res. 2010;27:1800-1811.
26. Longest PW, McLeskey JT, and Hindle M: Characterization of nanoaerosol size change during enhanced condensational growth. Aerosol Sci Technol. 2010;44:473-483.
27. Longest PW, and Hindle M: Numerical model to characterize the size increase of combination drug and hygroscopic excipient nanoparticle aerosols. Aerosol Sci Technol. 2011;45: 884-899.
28. Xi J, and Longest PW: Effects of oral airway geometry characteristics on the diffusional deposition of inhaled nanoparticles. J Biomech Eng. 2008;130:011008.
29. Xi J, and Longest PW: Numerical predictions of submicrometer aerosol deposition in the nasal cavity using a novel drift flux approach. Int J Heat Mass Transf. 2008;51: 5562-5577.
30. Cheng YS: Aerosol deposition in the extrathoracic region. Aerosol Sci Technol. 2003;37:659-671. (Pubitemid 39280174)
31. Longest PW, and Hindle M: Condensational growth of combination drug-excipient submicrometer particles: comparison of CFD predictions with experimental results. Pharm Res. 2012;29:707-721.
32. Longest PW, Tian G, Li X, Son Y-J, and Hindle M: Performance of combination drug and hygroscopic excipient submicrometer particles from a Soft Mist Inhaler in a characteristic model of the airways. Ann Biomed Eng. 2012. [Epub ahead of print]
33. Tian G, Longest PW, Su G, and Hindle M: Characterization of respiratory drug delivery with enhanced condensational growth (ECG) using an individual path model of the entire tracheobronchial airways. Ann Biomed Eng. 2011;39:1136-1153.
34. Xi J, and Longest PW: Transport and deposition of microaerosols in realistic and simplified models of the oral airway. Ann Biomed Eng. 2007;35:560-581. (Pubitemid 46448162)
35. Cheng KH, Cheng YS, Yeh HC, and Swift DL: Measurements of airway dimensions and calculation of mass transfer characteristics of the human oral passage. J Biomech Eng. 1997;119:476-482. (Pubitemid 27516447)
36. Yeh HC, and Schum GM: Models of human lung airways and their application to inhaled particle deposition. Bull Math Biol. 1980;42:461-480. (Pubitemid 10092310)
37. ICRP: Human Respiratory Tract Model for Radiological Protection. Elsevier Science Ltd., New York, 1994.
38. Heistracher T, and Hofmann W: Physiologically realistic models of bronchial airway bifurcations. J Aerosol Sci. 1995;26:497-509.
39. Horsfield K, Dart G, Olson DE, and Cumming G: Models of the human bronchial tree. J Applied Physiol. 1971;31:207-217.
40. Hammersley JR, and Olson DE: Physical models of the smaller pulmonary airways. J Applied Physiol. 1992;72: 2402-2414.
41. Russo J, Robinson R, and Oldham MJ: Effects of cartilage rings on airflow and particle deposition in the trachea and main bronchi. Med Eng Phys. 2008;30:581-589. (Pubitemid 351749849)
42. Tian G, Longest PW, Su G, Walenga RL, and Hindle M: 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;42:781-799.
43. Longest PW, 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. 2007;29:350-366. (Pubitemid 44880187)
44. Vinchurkar S, and Longest PW: Evaluation of hexahedral, prismatic and hybrid mesh styles for simulating respiratory aerosol dynamics. Comput Fluids. 2008;37: 317-331. (Pubitemid 350286469)
45. Phalen RF, Yeh HC, Schum GM, and Rabbe OG: Application of an idealized model to morphometry of the mammalian tracheobronchial tree. Anat Rec. 1978;190:167-176. (Pubitemid 8304466)
46. Longest PW, Tian G, Delvadia R, and HindleM: Development of a stochastic individual path (SIP) model for predicting the deposition of pharmaceutical aerosols: effects of turbulence, polydisperse aerosol size, and evaluation of multiple lung lobes. Aerosol Sci Technol. 2012. DOI: 10.1080/02786826.2012. 708799.
47. Longest PW, and Hindle M: 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.
48. Longest PW, Hindle M, Das Choudhuri S, and Xi J: 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.
49. Longest PW, and Vinchurkar S: Validating CFD predictions of respiratory aerosol deposition: effects of upstream transition and turbulence. J Biomech. 2007;40:305-316. (Pubitemid 44958582)
50. Xi J, Longest PW, and Martonen TB: Effects of the laryngeal jet on nano-and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways. J Appl Physiol. 08;104:1761-1777.
51. Longest PW, Hindle M, Das Choudhuri S, and Byron PR: Numerical simulations of capillary aerosol generation: CFD model development and comparisons with experimental data. Aerosol Sci Technol. 2007;41:952-973. (Pubitemid 47394484)
52. Longest PW, and Holbrook LT: In silico models of aerosol delivery to the respiratory tract-development and applications. Adv Drug Deliv Rev. 2012;64:296-311.
53. Longest PW, and Xi J: Effectiveness of direct Lagrangian tracking models for simulating nanoparticle deposition in the upper airways. Aerosol Sci Technol. 2007;41:380-397. (Pubitemid 46393082)
54. Vinchurkar S, Longest PW, and Peart J: CFD simulations of the Andersen cascade impactor: model development and effects of aerosol charge. J Aerosol Sci. 2009;40: 807-822.
55. Son Y-J, Longest PW, and Hindle M: Aerosolization characteristics of dry powder inhaler formulations for the enhanced excipient growth application: effect of DPI design. Respiratory Drug Delivery. 2012;3:903-906.
56. Son Y-J, Longest PW, and Hindle M: Aerosolization characteristics of dry powder inhaler formulations for the enhanced excipient growth application: effect of spray drying conditions. Respiratory Drug Delivery. 2012;3:899-902.
57. Ferron GA, Haider B, and Kreyling WG: Conditions for measuring supersaturation in the human lung using aerosols. J Aerosol Sci. 1984;15:211-215. (Pubitemid 14047026)
58. Kleinstreuer C, Zhang Z, and Donohue JF: Targeted drugaerosol delivery in the human respiratory system. Annu Rev Biomed Eng. 2008;10:195-220.
59. Kleinstreuer C, Shi H, and Zhang Z: Computational analyses of a pressurized metered dose inhaler and a new drugaerosol targeting methodology. J Aerosol Med. 2007;20:294-309. (Pubitemid 47469676)
60. Selting K, Essman S, Reinero C, Branson KR, Henry CJ, Owen N, Guntur VP, Waldrep JC, Kim DY, and Dhand R: Targeted combined aerosol chemotherapy in dogs and radiologic toxicity grading. J Aerosol Med Pulm Drug Deliv. 2011;24:43-48.
61. Murgia X, Gastiasoro E, Mielgo V, Ruiz-del-Yerro E, Alvarez-Diaz FJ, Lafuente H, Valls-i-Soler A, Gomez-Solaetxe MA, and Rey-Santano C: Surfactant and perfluorocarbon aerosolization during different mechanical ventilation strategies by means of inhalation catheters: an in vitro study. J Aerosol Med Pulm Drug Deliv. 2012;25:23-31.
62. Xie Y, Zeng P, Siegel R, Wiedmann TS, Hammer BE, and Longest PW: Magnetic deposition of aerosols composed of aggregated superparamagnetic nanoparticles. Pharm Res. 2010;27:855-865.
63. Xie YY, Longest PW, Xu YH, Wang JP, and Wiedmann TS: In vitro and in vivo lung deposition of coated magnetic aerosol particles. J Pharm Sci. 2010;99:4658-4668.
64. Redman GES, Martin AR, Waszak P, Thompson RB, Cheung PY, Thebaud B, and Finlay WH: Pilot study of inhaled aerosols targeted via magnetic alignment of high aspect ratio particles in rabbits. J Nanomater. 2011;130721.
65. Scheuch G, Bennett W, Borgstrom L, Clark A, Dalby R, Dolovich M, Fleming J, Gehr P, Gonda I, O'Callaghan C, Taylor G, and Newman S: Deposition, imaging, and clearance: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23:S39-S57.
66. Newman SP, Pitcairn GR, Hirst PH, Bacon RE, O'Keefe E, Reiners M, and Hermann R: Scintigraphic comparison of budesonide deposition from two dry powder inhalers. Eur Respir J. 2000;16:178-183. (Pubitemid 30480147)
67. Kraft M, Djukanovic R, Wilson S, Holgate ST, and Martin RJ: Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med. 1996;154:1505-1510. (Pubitemid 26391205)
68. Haley KJ, Sunday ME, Wiggs BR, Kozakewich HP, Reilly JJ, Mentzer SJ, Sugarbaker DJ, Doerschuk CM, and Drazen JM: Inflammatory cell distribution within and along asthmatic airways. Am J Respir Crit Care Med. 1998;158:565-572. (Pubitemid 28378188)
69. Kotaru C, Coreno A, Skowronski M, Muswick G, Gilkeson RC, and McFadden ER: Morphometric changes after thermal and methacholine bronchoprovocations. J Appl Physiol. 2005;98:1028-1036. (Pubitemid 40283685)
70. Tgavalekos NT, Tawhai M, Harris RS, Mush G, Vidal-Melo M, Venegas JG, and Lutchen KR: Identifying airways responsible for heterogeneous ventilation and mechanical dysfunction in asthma: an image functional modeling approach. J Appl Physiol. 2005;99:2388-2397. (Pubitemid 41691662)
71. Souza CA, Muller NL, Flint J, Wright JL, and Churg A: Idiopathic pulmonary fibrosis: spectrum of high-resolution CT findings. Am J Roentgenol. 2005;185:1531-1539.
72. Patton JS, Brain JD,Davies LA, Fiegel J, GumbletonM, Kim KJ, Sakagami M, Vanbever R, and Ehrhardt C: The particle has landed-characterizing the fate of inhaled pharmaceuticals. J Aerosol Med Pulm Drug Deliv. 2010;23:S71-S87.
73. Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M, Sasano H, Kondo T, and Nukiwa T: Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2004;169: 1203-1208. (Pubitemid 38680397)
74. Stahlhofen W, Rudolf G, and James AC: Intercomparison of experimental regional aerosol deposition data. J Aerosol Med. 1989;2:285-308.
75. Chan H-K: Dry powder aerosol drug delivery-opportunities for colloid and surface scientists. Colloids Surf A Physicochem Eng Aspects. 2006;284-285:50-55. (Pubitemid 43870203)
76. Finlay WH: Estimating the type of hygroscopic behavior exhibited by aqueous droplets. J Aerosol Med. 1998;11: 221-229. (Pubitemid 28563961)
77. Finlay WH, and Stapleton KW: The effect on regional lung deposition of coupled heat and mass-transfer between hygroscopic droplets and their surrounding phase. J Aerosol Sci. 1995;26:655-670.
78. Longest PW, Spence BM, Holbrook LT, Mossi KM, Son Y-J, and Hindle M: Production of inhalable submicrometer aerosols from conventional mesh nebulizers for improved respiratory drug delivery. J Aerosol Sci. 2012;51:66-80.
79. Longest PW, and Hindle M: CFD simulations of enhanced condensational growth (ECG) applied to respiratory drug delivery with comparisons to in vitro data. J Aerosol Sci. 2010;41:805-820.
80. Kim CS: Deposition of aerosol particles in human lungs: in vivo measurement and modeling. Biomarkers. 2009;14(S1): 54-58.
81. Clark AR, and Hartman MS: Regional lung deposition: can it be controlled and have an impact on safety and efficacy? Respiratory Drug Delivery. 2012;1:89-100.