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The Impact of Inspiratory Flow Rate on Drug Delivery to the Lungs with Dry Powder Inhalers

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Abstract

Current marketed dry powder inhalers utilize the energy from patient inspiration to fluidize and disperse bulk powder agglomerates into respirable particles. Variations in patient inspiratory flow profiles can lead to marked differences in total lung dose (TLD), and ultimately patient outcomes for an inhaled therapeutic. The present review aims to quantitate the flow rate dependence in TLD observed for a number of drug/device combinations using a new metric termed the Q index. With this data in hand, the review explores key attributes in the design of the formulation and device that impact flow rate dependence. The review also proposes alternative in vitro methods to assess flow rate dependence that more closely align with in vivo observations. Finally, the impact of variations in flow rate on lung function for inhaled bronchodilators is summarized.

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Abbreviations

d 2 a Q :

Inertial impaction parameter

(d 2 a Q)i :

Inertial impaction parameter for particles depositing in impactor

∆P:

Pressure drop

∆Q:

Difference in flow rates at two specified pressure drops

A:

Asthmatic patient

AIT:

Alberta idealized throat

C:

Central region of lungs

Cc :

Cunningham correction factor

CF:

Cystic fibrosis

CFU:

Colony forming units

COPD:

Chronic obstructive pulmonary disease

CV:

Coefficient of variation

D:

Characteristic dimension of the obstacle (typically its diameter)

da :

Aerodynamic diameter

DD:

Delivered dose

dg :

Geometric particle diameter

EXH:

Exhaled fraction

FEV1 :

Forced expiratory volume at one second

FPD:

Fine particle dose

FPD<3.3 μm :

Fine particle dose less than 3.3 μm

FPD<5 μm :

Fine particle dose less than 5 μm

FPDS3-F :

Fine particle dose on stage 3 to filter

FPDS4-F :

Fine particle dose on stage 4 to filter

HV:

Healthy volunteers

I:

Intermediate region of lungs

IVIVC:

In vitro – in vivo correlation

LB:

Lactose blend

lQ indexl:

Absolute value of the Q index

MMAD:

Mass median aerodynamic diameter

P:

Peripheral region of lungs

P/(C+I):

Ratio of peripheral deposition to deposition in the central and intermediate regions of the lungs

P/C:

Ratio of peripheral to central deposition in the lungs

PIF:

Peak inspiratory flow rate

PP:

Porous particles

p-value:

Calculated probability

Q:

Volumetric flow rate

Q index:

Metric for assessing flow rate dependence

R:

Intrinsic device resistance

r2 :

Statistical measure of closeness of fit

SABA:

Short-acting beta-agonist

Stk:

Stokes number

TLD:

Total lung dose

TLD1kPa :

Total lung dose at a 1 kPa pressure drop

TLD6kPa :

Total lung dose at a 6 kPa pressure drop

URT:

Upper respiratory tract

η:

Viscosity of air

ρp :

Particle density

References

  1. Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37:1308–31.

    Article  CAS  PubMed  Google Scholar 

  2. Stahlhofen W, Rudolf G, James AC. Intercomparison of regional deposition data. J Aerosol Med. 1989;2:285–308.

    Article  Google Scholar 

  3. Borgström L, Olsson B, Thorsson L. Degree of throat deposition can explain the variability in lung deposition of inhaled drugs. J Aerosol Med. 2006;19:473–83.

    Article  PubMed  Google Scholar 

  4. Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005;172:1497–504.

    Article  PubMed  Google Scholar 

  5. Newman S, Hirst P, Pitcairn G, Clark A. Understanding regional lung deposition data in gamma scintigraphy. Proc Respir Drug Deliv VI. 1998;1:9–15.

    Google Scholar 

  6. Carstairs JR, Nimmo AJ, Barnes PJ. Autoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis. 1985;132:541–7.

    CAS  PubMed  Google Scholar 

  7. Zanen P, Go LT, Lammers J-W. The optimal particle size of β-adrenergic aerosols in mild asthmatics. Int J Pharm. 1994;107:211–7.

    Article  CAS  Google Scholar 

  8. Zanen P, Go LT, Lammers J-W. The optimal particle size for parasympathicolytic aerosols. Int J Pharm. 1995;114:111–5.

    Article  CAS  Google Scholar 

  9. Zanen P, Go LT, Lammers J-W. Optimal particle size for β2 agonist and anticholinergic aerosols in patients with severe airflow obstruction. Thorax. 1996;51:977–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Patel P, Mukai D, Wilson AF. Dose response effects of two sizes of monodisperse isoproterenol in mild asthma. Am Rev Respir Dis. 1990;141:357–60.

    Article  CAS  PubMed  Google Scholar 

  11. Johnson MA, Newman SP, Bloom R, Talee N, Clarke SW. Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma. Chest. 1989;96:6–10.

    Article  CAS  PubMed  Google Scholar 

  12. Clark AR, Hartman MS. Regional lung deposition: can it be controlled and have an impact on safety and efficacy. Proc Respir Drug Deliv. 2012;1:89–100.

    Google Scholar 

  13. Enright PL, Beck KC, Sherrill DL. Repeatability of spirometry in 18,000 adult patients. Am J Respir Crit Care Med. 2004;169:235–8.

    Article  PubMed  Google Scholar 

  14. Clark A, Hollingworth A. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers – implications in in vitro testing. J Aerosol Med. 1995;6:99–110.

    Article  Google Scholar 

  15. Clark AR. The role of inspiratory pressures in determining the flow rates through dry powder inhalers: a review. Curr Pharm Design. 2015;21:3974–83.

    Article  CAS  Google Scholar 

  16. Everard ML, Devadason SG, Le Souëf PN. Flow early in the inspiratory maneuver affects the aerosol particle size distribution from a Turbuhaler. Respir Med. 1997;91:624–8.

    Article  CAS  PubMed  Google Scholar 

  17. Pitcairn G, Reader S, Pavia D, 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 powder inhaler. J Aerosol Med. 2005;18:264–72.

    Article  CAS  PubMed  Google Scholar 

  18. Newman SP, Hirst PH, Pitcairn GR. Scintigraphic evaluation of lung deposition with a novel inhaler device. Curr Opin Pulm Med. 2001;7 Suppl 1:S12–4.

    PubMed  Google Scholar 

  19. Pitcairn GR, Lim J, Hollingworth A, Newman SP. Scintigraphic assessment of drug delivery from the Ultrahaler dry powder inhaler. J Aerosol Med. 1997;10:295–306.

    Article  CAS  PubMed  Google Scholar 

  20. Newman SP, Hollingworth A, Clark AR. Effect of different modes of inhalation on drug delivery from a dry powder inhaler. Int J Pharm. 1994;102:127–32.

    Article  CAS  Google Scholar 

  21. Duddu SP, Sisk SA, Walter YH, Tarara TE, Trimble K, Clark AR, et al. Improved lung delivery from a passive dry powder inhaler using an engineered PulmoSphere powder. Pharm Res. 2002;19:689–95.

    Article  CAS  PubMed  Google Scholar 

  22. Hirst PH, Newman SP, Clark DA, Hertog MGL. Lung deposition of budesonide from the novel dry powder inhaler Airmax™. Respir Med. 2002;96:389–96.

    Article  CAS  PubMed  Google Scholar 

  23. Borgström L, Bondesson E, Morén F, Trofast E, Newman SP. Lung deposition of budesonide inhaled via Turbuhaler®: a comparison with terbutaline sulphate in normal subjects. Eur Respir J. 1994;7:69–73.

    Article  PubMed  Google Scholar 

  24. Hill M, Vaughan L, Dolovich M. Dose targeting for dry powder inhalers. Proc Respir Drug Deliv V. 1996;1:197–208.

    Google Scholar 

  25. Newman SP, Morén F, Trofast E, Talaee N, Clarke SW. Terbutaline sulphate Turbuhaler: effect of inhaled flow rate on drug deposition and efficacy. Int J Pharm. 1991;74:209–13.

    Article  CAS  Google Scholar 

  26. Pitcairn G, Lunghetti G, Ventura P, Newman S. A comparison of the lung deposition of salbutamol inhaled from a new dry powder inhaler, at two inhaled flow rates. Int J Pharm. 1994;102:11–8.

    Article  CAS  Google Scholar 

  27. Olsson B, Borgström L, Asking L, Bondesson E. Effect of inlet throat on the correlation between measured fine particle dose and lung deposition. Proc Respir Drug Deliv V. 1996;1:273–81.

    Google Scholar 

  28. Pitcairn GR, Lankinen T, Seppälä O-P, Newman SP. Pulmonary drug delivery from the Taifun® dry powder inhaler is relatively independent of the patient’s inspiratory effort. J Aerosol Med. 2000;13:97–104.

    Article  CAS  PubMed  Google Scholar 

  29. Newman S, Malik S, Hirst P, Pitcairn G, Heide A, Pabst J, et al. Lung deposition of salbutamol in healthy human subjects from the MAGhaler® dry powder inhaler. Respir Med. 2002;96:1026–32.

    Article  CAS  PubMed  Google Scholar 

  30. DeLong M, Wright J, Dawson M, Meyer T, Sommerer K, Dunbar C. Dose delivery characteristics of the AIR® pulmonary delivery system over a range of inspiratory flow rates. J Aerosol Med. 2005;18:452–9.

    Article  CAS  PubMed  Google Scholar 

  31. Wildhaber JH, Devadason SG, Wilson JM, Roller C, Lagana T, Borgström L, et al. Lung deposition of budesonide from Turbuhaler® in asthmatic children. Eur J Pediatr. 1998;157:1017–22.

    Article  CAS  PubMed  Google Scholar 

  32. Devadason SG, Everard ML, MacEarlan C, Roller C, Summers QA, Swift P, et al. Lung deposition from the Turbuhaler® in children with cystic fibrosis. Eur Respir J. 1997;10:2023–8.

    Article  CAS  PubMed  Google Scholar 

  33. Newman SP, Sutton DJ, Segarra R, Lamarca R, de Miquel G. Lung deposition of aclidinium bromide from Genuair®, a multidose dry powder inhaler. Respiration. 2009;78:322–8.

    Article  CAS  PubMed  Google Scholar 

  34. Weers JG, Clark AR, Rao N, Ung K, Haynes A, Khindri SK, et al. In vitro-in vivo correlations observed with indacaterol-based formulations delivered with the Breezhaler®. J Aerosol Med Pulm Drug Deliv. 2015;28:268–80.

    Article  CAS  PubMed  Google Scholar 

  35. Ung KT, Rao N, Weers JG, Clark AR, Chan H-K. In vitro assessment of dose delivery performance of dry powders for inhalation. Aerosol Sci Technol. 2014;48:1099–110.

    Article  CAS  Google Scholar 

  36. Ung KT, Chan H-K. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance of certain dry powder inhalers. Eur J Pharm Sci. 2016;84:46–54.

    Article  CAS  PubMed  Google Scholar 

  37. Weers JG, Ung K, Le J, Rao N, Ament B, Axford G, et al. Dose emission characteristics of placebo PulmoSphere™ particles are unaffected by a subject’s inhalation maneuver. J Aerosol Med Pulm Drug Del. 2013;26:56–68.

    Article  CAS  Google Scholar 

  38. Clark AR. Beyond the throat: Preferred methods for assessing regional deposition in the lung. Proc Respir Drug Deliv. 2010;1:235–44.

    Google Scholar 

  39. Weers JG, Miller DP. Formulation design of dry powders for inhalation. J Pharm Sci. 2015;104:3259–88.

    Article  CAS  PubMed  Google Scholar 

  40. Finlay WH. The mechanics of inhaled pharmaceutical aerosols: an introduction. London: Academic; 2001.

    Google Scholar 

  41. Geldart D. Types of gas fluidization. Powder Technol. 1973;11:41–4.

    Google Scholar 

  42. Ganderton D. The generation of respirable clouds from coarse powder agglomerates. J Biopharm Sci. 1992;3:101–5.

    Google Scholar 

  43. Ganderton D, Kassem NM. Dry powder inhalers. In: Ganderton D, Jones T, editors. Advances in pharmaceutical sciences. London: Academic; 1992. p. 165–91.

    Google Scholar 

  44. Hersey JA. Ordered mixing: a new concept in powder mixing practice. Powder Technol. 1975;11:41–4.

    Article  Google Scholar 

  45. Zhou QT, Morton DA. Drug-lactose binding aspects in adhesive mixtures: controlling performance in dry powder formulations by altering lactose carrier surfaces. Adv Drug Deliv Rev. 2012;64:275–84.

    Article  CAS  PubMed  Google Scholar 

  46. Weers JG, Tarara TE. The PulmoSphere™ platform for pulmonary drug delivery. Ther Deliv. 2014;5:277–95.

    Article  CAS  PubMed  Google Scholar 

  47. Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, et al. Large porous particles for pulmonary drug delivery. Science. 1997;276:1868–72.

    Article  CAS  PubMed  Google Scholar 

  48. Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res. 2008;25:999–1022.

    Article  CAS  PubMed  Google Scholar 

  49. Weers JG, Bell J, Chan H-K, Cipolla D, Dunbar C, Hickey AJ, et al. Pulmonary formulations: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23 Suppl 2:S5–23.

    CAS  PubMed  Google Scholar 

  50. Islam N, Gladki E. Dry powder inhalers (DPIs) – a review of device reliability and innovation. Int J Pharm. 2008;360:1–11.

    Article  CAS  PubMed  Google Scholar 

  51. Cardwell ND, Zee J, Kadrichu NP, Rao NP, Clark AR. Flow field characterization of three dry powder inhalers. Proc Respir Drug Deliv. 2014;2:501–4.

    Google Scholar 

  52. White S, Bennett DB, Cheu S, Conley PW, Guzek DB, Gray S, et al. Exubera®: Pharmaceutical development of a novel product for pulmonary delivery of insulin. Diabetes Technol Ther. 2005;7:896–906.

    Article  CAS  PubMed  Google Scholar 

  53. Smith AE. Nektar’s pulmonary delivery system (PDS): designed for usability, safety, and reliability in the real world. Proc Respir Drug Deliv. 2006;1:37–9.

    Google Scholar 

  54. Aydin M, Watts A, Becker D, Reynolds E, Cook R, Yun J. A flow rate dependence comparison of the active MicroDose inhaler and a passive DPI for delivery of conventional and engineered formulations. Proc Repir Drug Deliv. 2010;3:675–9.

    Google Scholar 

  55. Zeng XM, Martin GP, Marriott C, Pritchard J. The influence of carrier morphology on drug delivery by dry powder inhalers. Int J Pharm. 2000;200:93–106.

    Article  CAS  PubMed  Google Scholar 

  56. Jones MD, Price R. The influence of fine excipient particles on the performance of carrier-based dry powder inhalation formulations. Pharm Res. 2006;23:1665–74.

    Article  CAS  PubMed  Google Scholar 

  57. Begat P, Morton DAV, Shur J, Kippax P, Staniforth JN, Price R. The role of force control agents in high-dose dry powder inhaler formulations. J Pharm Sci. 2009;98:2770–83.

    Article  CAS  PubMed  Google Scholar 

  58. 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;17:335–43.

    Article  PubMed  Google Scholar 

  59. Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev. 2007;6:67–74.

    CAS  Google Scholar 

  60. Patton JS, Fishburn CS, Weers JG. The lungs as a portal for systemic drug delivery. Proc Am Thor Soc. 2004;1:338–44.

    Article  CAS  Google Scholar 

  61. Newman SP, Chan H-K. In vitro / in vivo comparisons in pulmonary drug delivery. J Aerosol Med Pulm Drug Deliv. 2008;21:77–84.

    Article  CAS  PubMed  Google Scholar 

  62. Harper NJ, Gray S, de Groot J, Parker JM, Sadrzadeh N, Schuler C, et al. The design and performance of the Exubera pulmonary insulin delivery system. Diabetes Technol Ther. 2007;9 Suppl 1:S16–27.

    CAS  PubMed  Google Scholar 

  63. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4169B1_02_03-FDA-ClinPharm-Biopharm.pdf. Accessed 28 Mar 2016.

  64. Maltz D, Glusker M, Axford G, Postich M, Rao N, Ung K. A novel passive dry powder inhaler for unit dose delivery to the deep lung. Proc Respir Drug Deliv. 2008;2:669–73.

    Google Scholar 

  65. Haynes A, Geller D, Weers J, Ament B, Pavkov R, Malcolmson R, et al. Inhalation of tobramycin using simulated cystic fibrosis inhalation profiles. Pediatr Pulmonol. 2016. doi:10.1002/ppul.23451.

    PubMed  Google Scholar 

  66. Zhang Y, Gilbertson K, Finlay WH. In vivo-in vitro comparison of deposition of pharmaceutical aerosols in three mouth-throat models with QVAR® and Turbuhaler® inhalers. J Aerosol Med. 2007;20:227–35.

    Article  CAS  PubMed  Google Scholar 

  67. Ruzycki CA, Golshahi L, Vehring R, Finlay WH. 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;31:1525–35.

    Article  CAS  PubMed  Google Scholar 

  68. Olsson B, Borgström L, Lundbäck H, Svensson M. 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.

    Article  CAS  PubMed  Google Scholar 

  69. Delvadia R, Hindle M, Longest PW, Byron PR. In vitro tests for aerosol deposition II: IVIVCs for different dry powder inhalers in normal adults. J Aerosol Med Pulm Drug Deliv. 2013;26:138–44.

    Article  CAS  PubMed  Google Scholar 

  70. Altshuler B. Modeling of dose-response relationships. Environ Health Perspect. 1981;42:23–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pedersen S. How to use a Rotahaler. Arch Dis Child. 1986;61:11–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zainudin BMZ, Biddiscombe M, Tolfree SEJ, Short M, Spiro SG. Comparison of bronchodilator responses and deposition patterns of salbutamol from a pressurized metered dose inhaler, as a dry powder, and as a nebulized solution. Thorax. 1990;45:469–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ross DL, Schultz RK. Effect of inhalation flow rate on the dosing characteristics of dry powder inhaler (DPI) and metered dose inhaler (MDI) products. J Aerosol Med. 1996;9:215–26.

    Article  CAS  PubMed  Google Scholar 

  74. Pedersen S, Hansen OR, Fugelsang G. Influence of inspiratory flow rate upon the effect of a Turbuhaler. Arch Dis Child. 1990;65:308–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Engel T, Heinig JH, Madsen F, Nikander K. Peak inspiratory flow and inspiratory vital capacity of patients with asthma measured with and without a new dry powder inhaler device (Turbuhaler®). Eur Respir J. 1990;3:1037–41.

    CAS  PubMed  Google Scholar 

  76. Baba K, Tanaka H, Nishimura M, Yokoe N, Takahashi D, Yagi T, et al. Age-dependent deterioration of peak inspiratory flow with two kinds of dry powder corticosteroid inhalers (Diskus and Turbuhaler) and relationships with asthma control. J Aerosol Med Pulm Drug Deliv. 2011;24:293–300.

    Article  CAS  PubMed  Google Scholar 

  77. Amirav I, Newhouse MT, Mansour Y. Measurement of peak inspiratory flow with On-chick dial device to simulate low-resistance (Diskus) and high-resistance (Turbuhaler) dry powder inhalers in children with asthma. Pediatr Pulmonol. 2005;39:447–51.

    Article  PubMed  Google Scholar 

  78. Raissy HH, Davies L, Marshik P, Kelly HW. Inspiratory flow through dry powder inhalers (DPIs) in asthmatic children 2 to 12 years old. Pediatr Asthma Allergy Immunol. 2006;19:223–30.

    Article  Google Scholar 

  79. Von Berg A, Kremer HJ, Ellers-Lenz B, Conrad F, Erb K, Maus J, et al. Peak inspiratory flow rates generated through the Novolizer® and Turbuhaler® dry powder inhaler devices by children with stable and unstable asthma. J Aerosol Med. 2007;20:50–8.

    Article  Google Scholar 

  80. Kamps AWA, Brand PLP, Roodra RJ. Variation of peak inspiratory flow through dry powder inhalers in children with stable and unstable asthma. Pediatr Pulmonol. 2004;37:65–70.

    Article  PubMed  Google Scholar 

  81. Persson G, Olsson B, Soliman S. The impact of inspiratory effort on inspiratory flow through Turbuhaler® in asthmatic patients. Eur Respir J. 1997;10:681–4.

    Article  CAS  PubMed  Google Scholar 

  82. Engel T, Scharling B, Skovsted B, Heinig JH. Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes. Br J Clin Pharmacol. 1992;33:439–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Dolovich MB, Vanzielegham M, Hidinger K-G, Newhouse MT. Influence of inspiratory flow rate on the response to terbutaline sulphate inhaled via the Turbuhaler. Am Rev Respir Dis. 1988;137:A433.

    Google Scholar 

  84. Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002;34:91–100.

    Article  PubMed  Google Scholar 

  85. Geller DE. Aerosol antibiotics in cystic fibrosis. Respir Care. 2009;54:658–70.

    Article  PubMed  Google Scholar 

  86. Geller DE, Weers J, Heuerding S. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J Aerosol Med Pulm Drug Deliv. 2011;24:175–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Geller DE, Nasr SZ, Piggott S, Ho E, Angyalosi G, Higgins M. Tobramycin inhalation powder in cystic fibrosis patients: response by age group. Respir Care. 2014;59:388–98.

    Article  PubMed  Google Scholar 

  88. Pavkov R, Geller DE, Ament B, Heuerding S, Gupta A. Dynamic inspiratory flow characteristics through the T-326 dry powder inhaler in cystic fibrosis patients. Proc Respir Drug Deliv Eur. 2013;2:325–8.

    Google Scholar 

  89. Tiddens HA, Geller DE, Challoner P, Speirs RJ, Kesser KC, Overbeek SE, et al. Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six year and older. J Aerosol Med. 2006;19:456–65.

    Article  CAS  PubMed  Google Scholar 

  90. Sarinas PS, Robinson TE, Clark AR, Canfield J, Chitkara RK, Fick RB. Inspiratory flow rate and dynamic lung function in cystic fibrosis and chronic obstructive lung diseases. Chest. 1998;114:988–92.

    Article  CAS  PubMed  Google Scholar 

  91. DeHaan WH, Finlay WH. Predicting extrathoracic deposition from dry powder inhalers. J Aerosol Sci. 2004;35:309–31.

    Article  CAS  Google Scholar 

  92. Tiddens HAWM, Bos AC, Mouton JW, Devadason S, Janssens H. Inhaled antibiotics: dry or wet? Eur Resp J. 2014;44:1308–18.

    Article  CAS  Google Scholar 

  93. Jaques A, Daviskas E, Turton JA, McKay K, Cooper P, Stirling RG, Robertson CF, Bye PT, Lesouëf PN, Shadbolt B, Andersen SD, Charlton B. Inhaled mannitol improves lung function in cystic fibrosis. Chest. 2008;1388–1396.

  94. Pedersen S, Steffensen G. Fenoterol powder inhaler technique in children: influence of inspiratory flow rate and breath holding. Eur J Resp Dis. 1986;68:207–14.

    CAS  Google Scholar 

  95. Groth S, Dirksen H. Optimal inhalation procedure for the fenoterol powder inhaler. Eur J Respir Dis. 1983;64 Suppl 130:17–24.

    Google Scholar 

  96. Auty RM, Brown K, Neale MG, Snashall PD. Respiratory tract deposition of sodium cromoglycate is highly dependent upon technique of inhalation using the Spinhaler. Br J Dis Chest. 1987;81:371.

    Article  CAS  PubMed  Google Scholar 

  97. Nielsen KG, Skov M, Klug B, Ifversen M, Bisgaard H. Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer®. Eur Respir J. 1997;10:2105–9.

    Article  CAS  PubMed  Google Scholar 

  98. Nielsen KG, Auk IL, Bojsen K, Ifversen M, Klug B, Bisgaard H. Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow rates in asthmatic children. Eur Respir J. 1998;11:350–4.

    Article  CAS  PubMed  Google Scholar 

  99. Ruffin RE, Dolovich MB, Oldenburg FA, Newhouse MT. The preferential deposition of inhaled isoproterenol and propranolol in asthmatic patients. Chest. 1986;80:904–7.

    Article  Google Scholar 

  100. Zanen P, van Spiegel PI, van der Kolk H, Tushuizen E, Enthoven R. The effect of the inhalation flow on the performance of a dry powder inhalation system. Int J Pharm. 1992;81:199–203.

    Article  CAS  Google Scholar 

  101. Newhouse MT, Nantel NP, Chambers CB, Pratt B, Parry-Billings M. Clickhaler (a novel dry powder inhaler) provides similar bronchodilation to pressurized metered-dose inhaler, even at low flow rates. Chest. 1999;115:952–6.

    Article  CAS  PubMed  Google Scholar 

  102. Azouz W, Chetcuti P, Hosker HSR, Saralaya D, Stephenson J, Chrystyn H. The inhalation characteristics of patients when they use different inhalers. J Aerosol Med Pulm Drug Deliv. 2015;28:35–42.

    Article  PubMed  Google Scholar 

  103. Demoly P, Hagedoorn P, de Boer AH, Frijlink HW. The clinical relevance of dry powder performance for drug delivery. Respir Med. 2014;108:1195–203.

    Article  PubMed  Google Scholar 

  104. Corradi M, Chrystyn H, Cosio BG, Pirozynski M, Loukides S, Louis R, et al. NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclomethasone and formoterol to treat large and small airways in asthma. Expert Opin Drug Deliv. 2014;11:1497–506.

    Article  CAS  PubMed  Google Scholar 

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  1. Novartis Pharmaceuticals Corporation, 150 Industrial Road, San Carlos, California, 94070, USA

    Jeffry Weers

  2. Aerogen Pharma, San Mateo, California, USA

    Andy Clark

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Weers, J., Clark, A. The Impact of Inspiratory Flow Rate on Drug Delivery to the Lungs with Dry Powder Inhalers. Pharm Res 34, 507–528 (2017). https://doi.org/10.1007/s11095-016-2050-x

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