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Review

Design of dry powder inhalers to improve patient outcomes: it’s not just about the device

Pages 365-380 | Received 14 Dec 2023, Accepted 29 Feb 2024, Published online: 25 Apr 2024

References

  • Borgström L, Clark A, Olsson B. Introduction. 1000 years of pharmaceutical aerosols. What remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23(Suppl 2):S1–S4. doi: 10.1089/jamp.2010.0848
  • Smith IJ, Bell J, Bowman N, et al. Inhaler devices: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23(Suppl 2):S25–S37. doi: 10.1089/jamp.2010.0853
  • Newman S. Improving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery. Expert Opin Drug Deliv. 2014;11:365–378. doi: 10.1517/17425247.2014.873402
  • Pritchard JN, Giles RD. Opportunities in respiratory drug delivery. Ther Deliv. 2014;5:1261–1273. doi: 10.4155/tde.14.78
  • Pritchard JN What are meaningful device improvements for patients, providers, and payers? In: RN Dalby, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, Traini D, editors. Respiratory drug delivery Vol. 1. Richmond (VA): Virginia Commonwealth University; 2014. p. 217–227.
  • Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res. 2008;25(5):999–1022. doi: 10.1007/s11095-007-9475-1
  • Vehring R, Foss WR, Lechuga-Ballesteros D. Particle formation in spray drying. J Aerosol Sci. 2007;38:728–746. doi: 10.1016/j.jaerosci.2007.04.005
  • Weers JG, Tarara TE. The PulmoSphere™ platform for pulmonary drug delivery. Ther Deliv. 2014;8:647–661. doi: 10.4155/tde.14.3
  • Weers JG, Miller DP, Tarara TE. Spray-dried PulmoSphere™ formulations for inhalation comprising crystalline drug particles. AAPS Pharm Sci Tech. 2019;20:103. doi: 10.1208/s12249-018-1280-0
  • Glusker M, Axford G, Le J, et al. USSC-003: a modular breath-actuated multi-dose dry powder inhaler system with telehealth capability. In: Dalby R, Byron P, Peart J, Suman J, Farr S, Young P Traini D, editors. Respiratory drug delivery. Vol. 3. Richmond (VA): Virginia Commonwealth University; 2016. p. 449–453.
  • Glusker M, Chiao A, Axford G, et al. Multidose inhaler. U.S. Patent 10,967,139 B2. 2021.
  • Serafin C, Maltz D, Glusker M, et al. Aspirations for usability: successfully including human factors in the design of the USSC-003 inhaler. In: Dalby R, Byron P, Peart J, Suman J, Farr S, Young P Traini D, editors. Respiratory drug delivery. Vol. 3. Richmond (VA): Virginia Commonwealth University; 2016. p. 477–480.
  • Van Ganse E, Mork AC, Osman LM, et al. Factors affecting adherence to asthma treatment: patients and physician perspectives. Prim Care Respir J. 2003;12(2):46–51. doi: 10.1038/pcrj.2003.17
  • FDA Guidance Document. Applying human factors and usability engineering to medical devices. 2016. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/applying-human-factors-and-usability-engineering-medical-devices.
  • Lavorini F, Magnan A, Christophe Dubus J, et al. Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir med. 2008;102:593–604. doi: 10.1016/j.rmed.2007.11.003
  • Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37(6):1308–1331. doi: 10.1183/09031936.00166410
  • Kocks J, Bosnic-Anticevich S, van Cooten J, et al. Identifying critical inhalation technique errors in dry powder inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study. BMC Pulm Med. 2023;23:302. doi: 10.1186/s12890-023-02566-6
  • Sulaiman I, Seheult J, Sadasivuni N, et al. The impact of common inhaler errors on drug delivery: investigating critical errors with a dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2017;30:247–255. doi: 10.1089/jamp.2016.1334
  • Clark AR. The role of inspiratory pressures in determining the flow rates though dry powder inhalers: a review. Curr Pharm Des. 2015;21(27):3974–3983. doi: 10.2174/1381612821666150820105800
  • Clark AR, Weers JG, Dhand R. The confusing world of dry powder inhalers: It is all about inspiratory pressures, not inspiratory flow rates. J Aerosol Med Pulm Drug Deliv. 2020;33:1–11. doi: 10.1089/jamp.2019.1556
  • Clark AR, Hollingworth AM. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers — implications for in vitro testing. J Aerosol Med. 1993;6(2):99–110. doi: 10.1089/jam.1993.6.99
  • Harris D. The advantages of designing high resistance swirl chambers for use in dry powder inhalers. ONdrugDelivery. 2015;57:10–13.
  • De Koning JP, Van der Mark TW, Coenegracht PMJ, et al. Effect of an external resistance to airflow on the inspiratory flow curve. Int J Pharm. 2002;234:257–266. doi: 10.1016/S0378-5173(01)00969-3
  • Azouz W, Chetcuti P, Hosker H, et al. Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study. BMC Pulm Med. 2015;15(1):47. doi: 10.1186/s12890-015-0043-x
  • Altman P, Wehbe L, Dederichs J, et al. Comparison of peak inspiratory flow rate via the Breezhaler®, Ellipta® and HandiHaler® dry powder inhalers in patients with moderate to very severe COPD: a randomized cross-over trial. BMC Pulm Med. 2018;18(1):100. doi: 10.1186/s12890-018-0662-0
  • Tiddens HA, Geller DE, Challoner P, et al. Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older. J Aerosol Med. 2006;19:456–465. doi: 10.1089/jam.2006.19.456
  • Sahay S, Holy R, Lyons S, et al. Impact of human behavior on inspiratory flow profiles in patients with pulmonary arterial hypertension using AOS™ dry powder inhaler device. Pulm Circ. 2021;11:1–9. doi: 10.1177/2045894020985345
  • Weers JG, Ung K, Le J, et al. Dose emission characteristics of placebo PulmoSphere ® particles are unaffected by a subject’s inhalation maneuver. J Aerosol Med Pulm Drug Deliv. 2013;26(1):56–68. doi: 10.1089/jamp.2012.0973
  • Ament BJ, Weers JG, Maltz DS, et al. Analysis of inhalation profiles in elderly COPD subjects. In: Dalby R, Byron P, Peart J, Suman J, Farr S Young P, editors. Respiratory drug delivery. Vol. 3. Richmond (VA): Virginia Commonwealth University; 2012. p. 613–616.
  • Broeders MEAC, Molema J, Hop WCJ, et al. The course of inhalation profiles during an exacerbation of obstructive lung disease. Respir med. 2004;98:1173–1179. doi: 10.1016/j.rmed.2004.04.010
  • Corradi M, Chrystyn H, Cosio BG, 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(9):1497–1506. doi: 10.1517/17425247.2014.928282
  • Chetta A, Yorgancioglu A, Scuri M, et al. Inspiratory flow profile and usability of the NEXThaler, a multidose dry powder inhaler, in asthma and COPD. BMC Pulm Med. 2021;21:65. doi: 10.1186/s12890-021-01430-9
  • Clark AR, Chambers CB, Muir D, et al. The effect of biphasic inhalation profiles on the deposition and clearance of coarse (6.5 μ m) bolus aerosols. J Aerosol Med. 2007;20(1):75–82. doi: 10.1089/jam.2006.0557
  • Everard ML, Devadason SG, Le Souef PN. Flow early in the inspiratory maneuver affects the aerosol particle size distribution from a turbuhaler. Respir med. 1997;91(10):624–628. doi: 10.1016/s0954-6111(97)90009-3
  • Haynes A, Geller D, Weers J, et al. Inhalation of tobramycin using simulated cystic fibrosis patient profiles. Pediatr Pulmonol. 2016;51:1159–1167. doi: 10.1002/ppul.23451
  • Farkas A, Lewis D, Church T, et al. Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler. Int J Pharm. 2017;533(1):225–235. doi: 10.1016/j.ijpharm.2017.09.057
  • Vartiainen VA, Lavorini F, Murphy AC, et al. High inhaler resistance does not limit successful inspiratory maneuver among patients with asthma or COPD. Expert Opin Drug Deliv. 2023;20:385–393. doi: 10.1080/17425247.2023.2179984
  • Weers JG, Son Y-J, Glusker M, et al. Idealhalers versus realhalers: is it possible to bypass deposition in the upper respiratory tract? J Aerosol Med Pulm Drug Deliv. 2019;32:55–69. doi: 10.1089/jamp.2018.1497
  • Cardwell ND, Zee J, Kadrichu NP, et al. Flow field characterization of three dry powder inhalers. In: Dalby R, Byron P, Peart J, Suman J, Farr S, Young P Traini D, editors. Respiratory drug delivery. Vol. 2. Richmond (VA): Virginia Commonwealth University; 2014. p. 501–504.
  • Cook CD, Mead J, Orzalesi MM. Static volume-pressure characteristics of the respiratory system during maximal efforts. J Appl Physiol. 1964;19(5):1016–1022. doi: 10.1152/jappl.1964.19.5.1016
  • Molimard M, Raherison C, Lignot S, et al. Assessment of handling of inhaler devices in real life: an observational study in 3811 patients in primary care. J Aerosol Med. 2003;16:249–254. doi: 10.1089/089426803769017613
  • Price DB, Roman-Rodriguez M, McQueen RB, et al. Inhaler errors in the CRITIKAL study: type, frequency, and associated with asthma outcomes. J Allergy Clin Immunol Pract. 2017;5(4):1071–1081. doi: 10.1016/j.jaip.201701.004
  • Farkas A, Tomisa G, Kugler S, et al. The effect of exhalation before the inhalation of dry powder aerosol drugs, emitted doses, and aerosol size distributions. Int J Pharm. 2023;5:100167. doi: 10.1016/j.ijpx.2023.100167
  • Weers JG, Clark AR. The impact of inspiratory flow rate on drug delivery to the lungs with dry powder inhalers. Pharm Res. 2017;34(3):507–528. doi: 10.1007/s-11095-016-2050-x
  • DeBoer AH, Chan H-K, Price R. A critical review on lactose-based drug formulation and device studies for dry powder inhalation: which are relevant and what interactions to expect? Adv Drug Deliv Rev. 2012;64(3):257–274. doi: 10.1016/j.addr.2011.04.004
  • Hebbink G, Jaspers M, Peters H, et al. Recent developments in lactose blends for carrier-based dry powder inhalation. Adv Drug Deliv Rev. 2022;189:114527. doi: 10.1016/j.addr.2022.114527
  • Begat P, Morton DAV, Staniforth JN, et al. The cohesive adhesive balances in dry powder inhaler formulations I: direct quantification by atomic force microscopy. Pharm Res. 2004;21(9):1591–1597. doi: 10.1023/b:pham.0000041453.24419.8a
  • Darquenne C. Deposition mechanisms. J Aerosol Med Pulm Drug Deliv. 2020;33:181–185. doi: 10.1089/jamp.2020.29029.cd
  • Darquenne C, vanErtbruggen C, Prisk GK. Convective flow dominates aerosol delivery to the lung segments. J Appl Physiol. 2011;111:48–54. doi: 10.1152/japplphysiol.00796.2010
  • Martin AR, Finlay WH. A general, algebraic equation for predicting total respiratory tract deposition of micrometer-sized aerosol particles in humans. J Aerosol Sci. 2007;38(2):246–253. doi: 10.1016/j.jaerosci.2006.11.002
  • Stahlhofen W, Rudolf G, James AC. Intercomparison of experimental regional deposition data. J Aerosol Med. 1989;2(3):285–308. doi: 10.1089/jam.1989.2.285
  • Borgström L, Olsson B, Thorsson L. Degree of throat deposition can explain the variability in lung deposition of inhaled drugs. J Aerosol Med. 2006;19:473–483. doi: 10.1089/jam.2006.19.473
  • Clark AR, Egan M. Modelling the deposition of inhaled powdered drug aerosols. J Aerosol Sci. 1994;25(1):175–186. doi: 10.1016/0021-8502
  • Weers JG, Clark AR, Rao N, et al. In vitro–in vivo correlations observed with indacaterol-based formulations delivered with the breezhaler ®. J Aerosol Med Pulm Drug Deliv. 2015;28(4):268–280. doi: 10.1089/jamp.2014.1178
  • Shur J, Price R, Lewis D, et al. From single excipients to dual excipient platforms in dry powder inhaler products. Int J Pharm. 2016;514:374–383. doi: 10.1016/j.ijpharm.2016.05.057
  • Begat P, Price R, Harris H, et al. The influence of force control agents on the cohesive-adhesive energy balance in dry powder inhaler formulations. Kona. 2005;23:109–121. doi: 10.14356/kona.2005014
  • Egan M, Nixon WA. A model of aerosol deposition in the lung for use in inhalation dose assessments. Radiat Prot Dosim. 1985;11:5–17. doi: 10.1016/0021-8502(94)90189-9
  • Miller DP, Tarara TE, Weers JG. Targeting of inhaled therapeutics to the small airways: nanoleucine carrier formulations. Pharmaceutics. 2021;13:1855. doi: 10.3390/pharmaceutics13111855
  • Leach CL, Kuehl PJ, Chand R, et al. Respiratory tract deposition of HFA–beclomethasone and HFA–fluticasone in asthmatic patients. J Aerosol Med Pulm Drug Deliv. 2016;29:127–133. doi: 10.1089/jamp.2014.1199
  • Lavorini F, Pedersen S, Usmani OS. Dilemmas, confusion, and misconceptions related to small airways directed therapy. Chest. 2017;151:1345–1355. doi: 10.1016/j.chest.2016.07.035
  • Usmani OS. Treating the small airways. Respiration. 2012;84:441–453. doi: 10.1159/000343629
  • Edwards DA, Hanes J, Caponetti G, et al. Large porous particles for pulmonary drug delivery. Science. 1997;276(5320):1868–1871. doi: 10.1126/science.276.5320.1868
  • Stevenson C, Bennett D. Development of Exubera insulin pulmonary delivery system. In: das Neves J, and Sarmento B, editors. Mucosal delivery of biopharmaceuticals. New York (NY): Springer; 2014. p. 461–481. Chapter 21.
  • Parks DJ, Rocchio MJ, Naydo K, et al. US Patent 6,267,155. 2001.
  • Stout G, Pham X, Rocchio MJ, et al. Powder filling apparatus and methods for their use. US Patent 6,182,712. 2001.
  • Lechuga-Ballesteros D, Charan C, Stults CL, et al. Trileucine improves aerosol performance and stability of spray-dried powders for inhalation. J Pharm Sci. 2008;97(1):287–302. doi: 10.1002/jps.21078
  • Ung KT, Rao N, Weers JG, et al. Design of spray-dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose. Int J Pharm. 2016;511(2):1070–1079. doi: 10.1016/j.ijpharm.2016.07.073
  • Geller D, Weers J, Heuerding S. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J Aerosol Med Pulm Drug Deliv. 2011;24(4):175–182. doi: 10.1089/jamp.2010.0855
  • McShane PJ, Weers JG, Tarara TE, et al. Ciprofloxacin dry powder for inhalation (CIP): technical design and features of an efficient drug-device combination. Pulm Pharmacol Ther. 2018;50:72–79. doi: 10.1016/j.pupt.2018.03.005
  • Weers JG. Comparison of phospholipid-based particles for sustained release of ciprofloxacin following pulmonary administration to bronchiectasis patients. Pulm Ther. 2019;5:127–150. doi: 10.1007/s41030-019-00104-6
  • Kugler AR, Lee JD, Samford LK, et al. Clinical pharmacokinetics (PK) following multiple doses of amphotericin B inhalation powder (ABIP). Focus on fungal infections (FoFI) 17. Abstract P-0032. 2007. p. 225–226.
  • Weers JG, Tarara T, Teung P, et al. Solving the particle adhesion paradox: respirable agglomerates of micronized drugs and porous (microcarrier) particles. In: Dalby R, Byron P, Peart J, Suman J, Young P Traini D, editors. Respiratory drug delivery Europe. Vol. 1. Richmond (VA): Virginia Commonwealth University; 2015. p. 177–185.
  • Vehring R, Lechuga-Ballesteros D, Joshi V, et al. Co-suspensions of microcrystals and engineered microparticles for uniform and efficient delivery of respiratory therapeutics from metered dose inhalers. Langmuir. 2012;28(42):15015–15023. doi: 10.1021/la302281n
  • Lechuga-Ballesteros D, Noga B, Vehring R, et al. Novel co-suspension metered dose inhalers for combination therapy of chronic obstructive pulmonary disease and asthma. Future Med Chem. 2011;3(13):1703–1718. doi: 10.4155/fmc.11.133
  • Usmani OS, Roche N, Jenkins M, et al. Consistent pulmonary drug delivery with whole lung deposition using the aerosphere inhaler: a review of the evidence. Int J COPD. 2021;16:113–124. doi: 10.2147/COPD.S274846
  • Ferguson GT, Hickey AJ, Dwivedi S. Co-suspension delivery technology in pressurized metered dose inhalers for multi-drug dosing in the treatment of respiratory diseases. Respir med. 2018;134:16–23. doi: 10.1016/j.rmed.2017.09.012
  • Mahler DA, Halpin DMG. Peak inspiratory flow as a predictive therapeutic biomarker in COPD. Chest. 2021;160:491–498. doi: 10.1016/j.chest2021.03.049
  • Ghosh S, Ohar JA, Drummond MB. Peak inspiratory flow rate in chronic obstructive pulmonary disease: implications for dry powder inhalers. J Aerosol Med Pulm Drug Deliv. 2017;30:381–387. doi: 10.1089/jamp.2017.1416
  • Christensen MC, Anthony SD, Roth EA. Seeing what’s next. Cambridge (MA): Harvard Business School Press; 2004.

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