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Published in: BMC Pulmonary Medicine 1/2019

Open Access 01-12-2019 | Mannitol | Research article

Aerosol drug delivery to the lungs during nasal high flow therapy: an in vitro study

Authors: Martin Wallin, Patricia Tang, Rachel Yoon Kyung Chang, Mingshi Yang, Warren H. Finlay, Hak-Kim Chan

Published in: BMC Pulmonary Medicine | Issue 1/2019

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Abstract

Background

Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 μm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim to develop an efficient nose-to-lung delivery system capable of delivering improved quantities (FPF > 16%) of dry powder aerosols to the lungs via an NHF system.

Methods

We evaluated the FPF of spray-dried mannitol with leucine with a next generation impactor connected to a nasopharyngeal outlet of an adult nasal airway replica. In addition, we investigated the influence of different dispersion (20–30 L/min) and inspiratory (20–40 L/min) flow rates, on FPF.

Results

We found an FPF of 32% with dispersion flow rate at 25 L/min and inspiratory flow rate at 40 L/min. The lowest FPF (21%) obtained was at the dispersion flow rate at 30 L/min and inspiratory flow rate at 30 L/min. A higher inspiratory flow rate was generally associated with a higher FPF. The nasal cannula accounted for most loss of aerosols.

Conclusions

In conclusion, delivering a third of inhalable powder to the lungs is possible in vitro through an NHF system using a low dispersion airflow and a highly dispersible powder. Our results may lay the foundation for clinical evaluation of powder aerosol delivery to the lungs during NHF therapy in humans.
Literature
1.
go back to reference Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council (MRC) Working Party. Lancet (London, England). 1981;1(8222):681–6. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council (MRC) Working Party. Lancet (London, England). 1981;1(8222):681–6.
2.
go back to reference Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial (NOTT) Group. Ann Intern Med. 1980;93(3):391–8. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial (NOTT) Group. Ann Intern Med. 1980;93(3):391–8.
3.
go back to reference Ward JJ. High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care. 2013;58(1):98–122.CrossRef Ward JJ. High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care. 2013;58(1):98–122.CrossRef
4.
go back to reference Ischaki E, Pantazopoulos I, Zakynthinos S. Nasal high flow therapy: a novel treatment rather than a more expensive oxygen device. Eur Respir Rev. 2017;26(145):1-14. Ischaki E, Pantazopoulos I, Zakynthinos S. Nasal high flow therapy: a novel treatment rather than a more expensive oxygen device. Eur Respir Rev. 2017;26(145):1-14.
5.
go back to reference Spoletini G, Alotaibi M, Blasi F, Hill NS. Heated humidified high-flow nasal oxygen in adults: mechanisms of action and clinical implications. Chest. 2015;148(1):253–61.CrossRef Spoletini G, Alotaibi M, Blasi F, Hill NS. Heated humidified high-flow nasal oxygen in adults: mechanisms of action and clinical implications. Chest. 2015;148(1):253–61.CrossRef
6.
go back to reference Soler-Cataluña JJ, Martínez-García MÁ, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(11):925–31.CrossRef Soler-Cataluña JJ, Martínez-García MÁ, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(11):925–31.CrossRef
7.
go back to reference Wilson R, Sethi S, Anzueto A, Miravitlles M. Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease. J Inf Secur. 2013;67(6):497–515. Wilson R, Sethi S, Anzueto A, Miravitlles M. Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease. J Inf Secur. 2013;67(6):497–515.
8.
go back to reference Miravitlles M, Anzueto A. Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188(9):1052–7.CrossRef Miravitlles M, Anzueto A. Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188(9):1052–7.CrossRef
9.
go back to reference Beeh KM, Burgel PR, Franssen FME, Lopez-Campos JL, Loukides S, Hurst JR, Flezar M, Ulrik CS, Di Marco F, Stolz D, et al. How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2017;196(2):139–49.CrossRef Beeh KM, Burgel PR, Franssen FME, Lopez-Campos JL, Loukides S, Hurst JR, Flezar M, Ulrik CS, Di Marco F, Stolz D, et al. How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2017;196(2):139–49.CrossRef
10.
go back to reference Dugernier J, Hesse M, Jumetz T, Bialais E, Roeseler J, Depoortere V, Michotte JB, Wittebole X, Ehrmann S, Laterre PF, et al. Aerosol delivery with two nebulizers through high-flow nasal cannula: a randomized cross-over single-photon emission computed tomography-computed tomography study. J Aerosol Med Pulm Drug Deliv. 2017;30(5):349–58.CrossRef Dugernier J, Hesse M, Jumetz T, Bialais E, Roeseler J, Depoortere V, Michotte JB, Wittebole X, Ehrmann S, Laterre PF, et al. Aerosol delivery with two nebulizers through high-flow nasal cannula: a randomized cross-over single-photon emission computed tomography-computed tomography study. J Aerosol Med Pulm Drug Deliv. 2017;30(5):349–58.CrossRef
11.
go back to reference Reminiac F, Vecellio L, Heuze-Vourc'h N, Petitcollin A, Respaud R, Cabrera M, Pennec DL, Diot P, Ehrmann S. Aerosol therapy in adults receiving high flow nasal cannula oxygen therapy. J Aerosol Med Pulm Drug Deliv. 2016;29(2):134–41.CrossRef Reminiac F, Vecellio L, Heuze-Vourc'h N, Petitcollin A, Respaud R, Cabrera M, Pennec DL, Diot P, Ehrmann S. Aerosol therapy in adults receiving high flow nasal cannula oxygen therapy. J Aerosol Med Pulm Drug Deliv. 2016;29(2):134–41.CrossRef
12.
go back to reference Réminiac F, Landel C, Gensburger S, Bocar T, Mordier L, Philippe M, Le Pennec D, Vecellio L, Ehrmann S: Optimal delivery of salbutamol with a pressurized metered dose inhaler within a high flow nasal therapy circuit. In: C51 RESPIRATORY FAILURE: HIGH FLOW OXYGEN, LIBERATION, NON-INVASIVE, AND PROLONGED VENTILATION. Edn.: American Thoracic Society; 2016: A5313. Réminiac F, Landel C, Gensburger S, Bocar T, Mordier L, Philippe M, Le Pennec D, Vecellio L, Ehrmann S: Optimal delivery of salbutamol with a pressurized metered dose inhaler within a high flow nasal therapy circuit. In: C51 RESPIRATORY FAILURE: HIGH FLOW OXYGEN, LIBERATION, NON-INVASIVE, AND PROLONGED VENTILATION. Edn.: American Thoracic Society; 2016: A5313.
13.
go back to reference Ari A, Harwood R, Sheard M, Dailey P, Fink JB. In vitro comparison of heliox and oxygen in aerosol delivery using pediatric high flow nasal cannula. Pediatr Pulmonol. 2011;46(8):795–801.CrossRef Ari A, Harwood R, Sheard M, Dailey P, Fink JB. In vitro comparison of heliox and oxygen in aerosol delivery using pediatric high flow nasal cannula. Pediatr Pulmonol. 2011;46(8):795–801.CrossRef
14.
go back to reference Bhashyam AR, Wolf MT, Marcinkowski AL, Saville A, Thomas K, Carcillo JA, Corcoran TE. Aerosol delivery through nasal cannulas: an in vitro study. J Aerosol Med Pulm Drug Deliv. 2008;21(2):181–8.CrossRef Bhashyam AR, Wolf MT, Marcinkowski AL, Saville A, Thomas K, Carcillo JA, Corcoran TE. Aerosol delivery through nasal cannulas: an in vitro study. J Aerosol Med Pulm Drug Deliv. 2008;21(2):181–8.CrossRef
15.
go back to reference Perry SA, Kesser KC, Geller DE, Selhorst DM, Rendle JK, Hertzog JH. Influences of cannula size and flow rate on aerosol drug delivery through the Vapotherm humidified high-flow nasal cannula system. Pediatr Crit Care Med. 2013;14(5):e250–6.CrossRef Perry SA, Kesser KC, Geller DE, Selhorst DM, Rendle JK, Hertzog JH. Influences of cannula size and flow rate on aerosol drug delivery through the Vapotherm humidified high-flow nasal cannula system. Pediatr Crit Care Med. 2013;14(5):e250–6.CrossRef
16.
go back to reference Okuda T, Tang P, Yu J, Finlay WH, Chan HK. Powder aerosol delivery through nasal high-flow system: in vitro feasibility and influence of process conditions. Int J Pharm. 2017;533(1):187–97.CrossRef Okuda T, Tang P, Yu J, Finlay WH, Chan HK. Powder aerosol delivery through nasal high-flow system: in vitro feasibility and influence of process conditions. Int J Pharm. 2017;533(1):187–97.CrossRef
17.
go back to reference Dhand R. Aerosol therapy in patients receiving noninvasive positive pressure ventilation. J Aerosol Med Pulm Drug Deliv. 2012;25(2):63–78.CrossRef Dhand R. Aerosol therapy in patients receiving noninvasive positive pressure ventilation. J Aerosol Med Pulm Drug Deliv. 2012;25(2):63–78.CrossRef
18.
go back to reference Young PM, Price R, Tobyn MJ, Buttrum M, Dey F. The influence of relative humidity on the cohesion properties of micronized drugs used in inhalation therapy. J Pharm Sci. 2004;93(3):753–61.CrossRef Young PM, Price R, Tobyn MJ, Buttrum M, Dey F. The influence of relative humidity on the cohesion properties of micronized drugs used in inhalation therapy. J Pharm Sci. 2004;93(3):753–61.CrossRef
19.
go back to reference Behara SR, Longest PW, Farkas DR, Hindle M. Development of high efficiency ventilation bag actuated dry powder inhalers. Int J Pharm. 2014;465(1–2):52–62.CrossRef Behara SR, Longest PW, Farkas DR, Hindle M. Development of high efficiency ventilation bag actuated dry powder inhalers. Int J Pharm. 2014;465(1–2):52–62.CrossRef
20.
go back to reference Longest PW, Golshahi L, Behara SR, Tian G, Farkas DR, Hindle M. Efficient nose-to-lung (N2L) aerosol delivery with a dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2015;28(3):189–201.CrossRef Longest PW, Golshahi L, Behara SR, Tian G, Farkas DR, Hindle M. Efficient nose-to-lung (N2L) aerosol delivery with a dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2015;28(3):189–201.CrossRef
21.
go back to reference Li L, Leung SSY, Gengenbach T, Yu J, Gao G, Tang P, Zhou Q, Chan H-K. Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation. Int J Pharm. 2017;530(1):30–9.CrossRef Li L, Leung SSY, Gengenbach T, Yu J, Gao G, Tang P, Zhou Q, Chan H-K. Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation. Int J Pharm. 2017;530(1):30–9.CrossRef
22.
go back to reference Li L, Sun S, Parumasivam T, Denman JA, Gengenbach T, Tang P, Mao S, Chan H-K. L-leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm. 2016;102:132–41.CrossRef Li L, Sun S, Parumasivam T, Denman JA, Gengenbach T, Tang P, Mao S, Chan H-K. L-leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm. 2016;102:132–41.CrossRef
23.
go back to reference Golshahi L, Noga M, Thompson R, Finlay W. In vitro deposition measurement of inhaled micrometer-sized particles in extrathoracic airways of children and adolescents during nose breathing. J Aerosol Sci. 2011;42(7):474–88.CrossRef Golshahi L, Noga M, Thompson R, Finlay W. In vitro deposition measurement of inhaled micrometer-sized particles in extrathoracic airways of children and adolescents during nose breathing. J Aerosol Sci. 2011;42(7):474–88.CrossRef
24.
go back to reference Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R: Large porous particles for pulmonary drug delivery. Science (New York, NY) 1997, 276(5320):1868–1871. Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R: Large porous particles for pulmonary drug delivery. Science (New York, NY) 1997, 276(5320):1868–1871.
25.
go back to reference Mitchell J: Practices of coating collection surfaces of cascade impactors: a survey of members of the European pharmaceutical aerosol group (EPAG). In: Drug Delivery to the Lungs-14. Vol. 1; 2003: 75–78. Mitchell J: Practices of coating collection surfaces of cascade impactors: a survey of members of the European pharmaceutical aerosol group (EPAG). In: Drug Delivery to the Lungs-14. Vol. 1; 2003: 75–78.
26.
go back to reference Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA. Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med. 2013;39(2):247–57.CrossRef Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA. Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med. 2013;39(2):247–57.CrossRef
27.
go back to reference Marple VA, Olson BA, Santhanakrishnan K, Mitchell JP, Murray SC, Hudson-Curtis BL. Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part II: archival calibration. J Aerosol Med. 2003;16(3):301–24.CrossRef Marple VA, Olson BA, Santhanakrishnan K, Mitchell JP, Murray SC, Hudson-Curtis BL. Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part II: archival calibration. J Aerosol Med. 2003;16(3):301–24.CrossRef
28.
go back to reference Marple VA, Olson BA, Santhanakrishnan K, Roberts DL, Mitchell JP, Hudson-Curtis BL. Next generation pharmaceutical impactor: a new impactor for pharmaceutical inhaler testing. Part III. Extension of archival calibration to 15 L/min. J Aerosol Med. 2004;17(4):335–43.CrossRef Marple VA, Olson BA, Santhanakrishnan K, Roberts DL, Mitchell JP, Hudson-Curtis BL. Next generation pharmaceutical impactor: a new impactor for pharmaceutical inhaler testing. Part III. Extension of archival calibration to 15 L/min. J Aerosol Med. 2004;17(4):335–43.CrossRef
29.
go back to reference Marple V, Roberts D, Mitchell J. A proposal for the use of the next generation pharmaceutical impactor (NGI) at flow rates between 15 and 30 L/min. In: Respiratory drug delivery. California: Palm Springs; 2004. p. 9. Marple V, Roberts D, Mitchell J. A proposal for the use of the next generation pharmaceutical impactor (NGI) at flow rates between 15 and 30 L/min. In: Respiratory drug delivery. California: Palm Springs; 2004. p. 9.
30.
go back to reference Warren DW, Hinton VA, Pillsbury HC 3rd, Hairfield WM. Effects of size of the nasal airway on nasal airflow rate. Arch Otolaryngol Head Neck Surg. 1987;113(4):405–8.CrossRef Warren DW, Hinton VA, Pillsbury HC 3rd, Hairfield WM. Effects of size of the nasal airway on nasal airflow rate. Arch Otolaryngol Head Neck Surg. 1987;113(4):405–8.CrossRef
31.
go back to reference Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res. 2013;3(1):42–62.CrossRef Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res. 2013;3(1):42–62.CrossRef
32.
go back to reference Crouse U, Laine-Alava MT. Effects of age, body mass index, and gender on nasal airflow rate and pressures. Laryngoscope. 1999;109(9):1503–8.CrossRef Crouse U, Laine-Alava MT. Effects of age, body mass index, and gender on nasal airflow rate and pressures. Laryngoscope. 1999;109(9):1503–8.CrossRef
33.
go back to reference Yang MY, Chan JG, Chan HK. Pulmonary drug delivery by powder aerosols. J Control Release. 2014;193:228–40.CrossRef Yang MY, Chan JG, Chan HK. Pulmonary drug delivery by powder aerosols. J Control Release. 2014;193:228–40.CrossRef
34.
go back to reference Islam N, Gladki E. Dry powder inhalers (DPIs)—a review of device reliability and innovation. Int J Pharm. 2008;360(1):1–11.CrossRef Islam N, Gladki E. Dry powder inhalers (DPIs)—a review of device reliability and innovation. Int J Pharm. 2008;360(1):1–11.CrossRef
35.
go back to reference Hinds WC. Aerosol technology: properties, behavior, and measurement of airborne particles. 2nd ed. Canada: John Wiley & Sons; 1998. Hinds WC. Aerosol technology: properties, behavior, and measurement of airborne particles. 2nd ed. Canada: John Wiley & Sons; 1998.
36.
go back to reference Kiaee M, Wachtel H, Noga ML, Martin AR, Finlay WH. Regional deposition of nasal sprays in adults: a wide ranging computational study. Int J Numer Method Biomed Eng. 2018:e2968. Kiaee M, Wachtel H, Noga ML, Martin AR, Finlay WH. Regional deposition of nasal sprays in adults: a wide ranging computational study. Int J Numer Method Biomed Eng. 2018:e2968.
37.
go back to reference Hahn I, Scherer PW, Mozell MM. Velocity profiles measured for airflow through a large-scale model of the human nasal cavity. J Appl Physiol. 1993;75(5):2273–87.CrossRef Hahn I, Scherer PW, Mozell MM. Velocity profiles measured for airflow through a large-scale model of the human nasal cavity. J Appl Physiol. 1993;75(5):2273–87.CrossRef
38.
go back to reference Yang MY, Ruzycki C, Verschuer J, Katsifis A, Eberl S, Wong K, Golshahi L, Brannan JD, Finlay WH, Chan H-K. Examining the ability of empirical correlations to predict subject specific in vivo extrathoracic aerosol deposition during tidal breathing. Aerosol Sci Technol. 2017;51(3):363–76.CrossRef Yang MY, Ruzycki C, Verschuer J, Katsifis A, Eberl S, Wong K, Golshahi L, Brannan JD, Finlay WH, Chan H-K. Examining the ability of empirical correlations to predict subject specific in vivo extrathoracic aerosol deposition during tidal breathing. Aerosol Sci Technol. 2017;51(3):363–76.CrossRef
39.
go back to reference Golshahi L, Noga ML, Vehring R, Finlay WH. An in vitro study on the deposition of micrometer-sized particles in the Extrathoracic Airways of Adults during Tidal Oral Breathing. Ann Biomed Eng. 2013;41(5):979–89.CrossRef Golshahi L, Noga ML, Vehring R, Finlay WH. An in vitro study on the deposition of micrometer-sized particles in the Extrathoracic Airways of Adults during Tidal Oral Breathing. Ann Biomed Eng. 2013;41(5):979–89.CrossRef
41.
go back to reference Morgan NJ, MacGregor FB, Birchall MA, Lund VJ, Sittampalam Y. Racial differences in nasal fossa dimensions determined by acoustic rhinometry. Rhinology. 1995;33(4):224–8.PubMed Morgan NJ, MacGregor FB, Birchall MA, Lund VJ, Sittampalam Y. Racial differences in nasal fossa dimensions determined by acoustic rhinometry. Rhinology. 1995;33(4):224–8.PubMed
Metadata
Title
Aerosol drug delivery to the lungs during nasal high flow therapy: an in vitro study
Authors
Martin Wallin
Patricia Tang
Rachel Yoon Kyung Chang
Mingshi Yang
Warren H. Finlay
Hak-Kim Chan
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Mannitol
Published in
BMC Pulmonary Medicine / Issue 1/2019
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-019-0807-9

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