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Review

Combining experimental and computational techniques to understand and improve dry powder inhalers

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 59-73 | Received 09 Nov 2021, Accepted 05 Jan 2022, Published online: 20 Jan 2022

References

  • Frijlink HW, De Boer AH. Dry powder inhalers for pulmonary drug delivery. Expert Opin Drug Deliv. 2004;1(1):67–86.
  • Islam N, Cleary MJ. Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery-a review for multidisciplinary researchers. Med Eng Phys. 2012;34(4):409–427.
  • Berkenfeld K, Lamprecht A, McConville JT. Devices for dry powder drug delivery to the lung. AAPS Pharmscitech. 2015;16(3):479–490.
  • MarketWatch. Inhalation and nasal spray generic drugs market 2021: 6.3% CAGR with top countries data, what will be the value of inhalation and nasal spray generic drugs industry by the end of 2026? 2021.
  • de Boer AH, Hagedoorn P, Hoppentocht M, et al. Dry powder inhalation: past, present and future. Expert Opin Drug Deliv. 2017;14(4): 499–512.
  • Friebel C, Steckel H. Single-use disposable dry powder inhalers for pulmonary drug delivery. Expert Opin Drug Deliv. 2010;7(12):1359–1372.
  • de Boer Ah, Hagedoorn P. The role of disposable inhalers in pulmonary drug delivery. Expert Opin Drug Deliv. 2015;12(1):143–157.
  • Weers J, Clark A. The impact of inspiratory flow rate on drug delivery to the lungs with dry powder inhalers. Pharm Res. 2017;34(3):507–528.
  • de Koning Jp, van der Mark Tw, Coenegracht PM, et al. Effect of an external resistance to airflow on the inspiratory flow curve. Int J Pharm. 2002;234(1–2):257–266.
  • Borgstrom L, Asking L, Thorsson L. Idealhalers or realhalers? A comparison of Diskus and Turbuhaler. Int J Clin Pract. 2005;59(12):1488–1495.
  • Selroos O, Borgstrom L, Ingelf J. Performance of turbuhaler((R)) in patients with acute airway obstruction and COPD, and in children with asthma: understanding the clinical importance of adequate peak inspiratory flow, high lung deposition, and low in vivo dose variability. Treat Respir Med. 2006;5(5):305–315.
  • Coates MS, Chan HK, Fletcher DF, et al. Influence of mouth piece geometry on the aerosol delivery performance of a dry powder inhaler. Pharm Res. 2007;24:1450–1456.
  • Coates MS, Chan HK, Fletcher DF, et al. Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 2: air inlet size. J Pharm Sci. 2006;95(6): 1382–1392.
  • Wong W, Fletcher DF, Traini D, et al. Particle aerosolisation and break-up in dry powder inhalers 1: evaluation and modelling of venturi effects for agglomerated systems. Pharm Res. 2010;27(7):1367–1376.
  • IndustryARC. Dry powder inhaler devices market - forecast (2021 - 2026). 2021.
  • Food and Drug Administration. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products–quality considerations. MD: FDA. 2018.
  • European Medicines Agency. Guidelines for pharmaceutical quality of inhalation and nasal products. 2016.
  • Therapeutic Goods Administration. Inhalation and nasal spray registered medicines. Australia: TGA. 2019.
  • Kuribayashi R, Yamaguchi T, Sako H, et al. Bioequivalence evaluations of generic dry powder inhaler drug products: similarities and differences between Japan, USA, and the European Union. Clin Pharmacokinet. 2017;56(3):225–233.
  • Lee SL, Saluja B, Garcia-Arieta A, et al. Regulatory considerations for approval of generic inhalation drug products in the US, EU, Brazil, China, and India. AAPS J. 2015;17(5):1285–1304.
  • Shu C, Liu R, Liu S, et al. Practical, modular, and general synthesis of 3-coumaranones through gold-catalyzed intermolecular alkyne oxidation strategy. Chem Asian J. 2015;10(1):91–95.
  • Food and Drug Administration. Combination product definition combination product types. MD: FDA. 2018.
  • Kopsch T, Murnane D, Symons D. A personalized medicine approach to the design of dry powder inhalers: selecting the optimal amount of bypass. Int J Pharm. 2017;529(1–2):589–596.
  • Ruzycki CA, Javaheri E, Finlay WH. The use of computational fluid dynamics in inhaler design. Expert Opin Drug Deliv. 2013;10(3):307–323.
  • Wong W, Fletcher DF, Traini D, et al. The use of computational approaches in inhaler development. Adv Drug Deliv Rev. 2012;64(4): 312–322.
  • Dos Reis LG, Chaugule V, Fletcher DF, et al. In-vitro and particle image velocimetry studies of dry powder inhalers. Int J Pharm. 2021;592:119966.
  • Fletcher DF, Chaugule V, Gomes Dos Reis L, et al. On the use of computational fluid dynamics (CFD) modelling to design improved dry powder inhalers. Pharm Res. 2021;38(2):277–288.
  • de Boer Ah, Hagedoorn P, Woolhouse R, et al. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer disposable high-dose dry powder inhaler. J Pharm Pharmacol. 2012;64(9):1316–1325.
  • Minocchieri S, Burren JM, Bachmann MA, et al. 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(2):141–146.
  • Abdel-Halim H, Traini D, Hibbs D, et al. Modelling of molecular phase transitions in pharmaceutical inhalation compounds: an in silico approach. Eur J Pharm Biopharm. 2011;78(1):83–89.
  • Ponzini R, Da Vià R, Bnà S, et al. Coupled CFD-DEM model for dry powder inhalers simulation: validation and sensitivity analysis for the main model parameters. Powder Technol. 2021;385:199–226.
  • Farkas D, Hindle M, Bonasera S, et al. Development of an inline dry powder inhaler for oral or trans-nasal aerosol administration to children. J Aerosol Med Pulm Drug Deliv. 2020;33(2):83–98.
  • Farkas D, Longest W. Development of a new inhaler for high efficiency dispersion of spray-dried powders using Computational Fluid Dynamics (CFD) modeling. AAPS J. 2019;2(25):1–29.
  • Longest PW, Bass K, Dutta R, et al. Use of computational fluid dynamics deposition modeling in respiratory drug delivery. Expert Opin Drug Deliv. 2019;16(1): 7–26.
  • Chen Y, Young PM, Murphy S, et al. High-speed laser image analysis of plume angles for pressurised metered dose inhalers: the effect of nozzle geometry. AAPS Pharmscitech. 2017;18(3):782–789.
  • Huang R, Nedanoski A, Fletcher DF, et al. An automated segmentation framework for nasal computational fluid dynamics analysis in computed tomography. Comput Biol Med. 2019;115:103505.
  • Wong W, Fletcher DF, Traini D, et al. Particle aerosolisation and break-up in dry powder inhalers: evaluation and modelling of impaction effects for agglomerated systems. J Pharm Sci. 2011;100(7): 2744–2754.
  • Zheng Z, Leung SSY, Gupta R. Flow and particle modelling of dry powder inhalers: methodologies, recent development and emerging applications. Pharmaceutics. 2021;13(2):189.
  • Tashkin DP, Koltun A, Wallace R. A generic fluticasone propionate and salmeterol dry powder inhaler: evidence of usability, function, and robustness. Allergy Asthma Proc. 2021;42(1):30–35.
  • de Boer Ah, Gjaltema D, Hagedoorn P, et al. Can ‘extrafine’ dry powder aerosols improve lung deposition? Eur J Pharm Biopharm. 2015;96:143–151.
  • Ruzycki CA, Martin AR, Vehring R, et al. An in vitro examination of the effects of altitude on dry powder inhaler performance. J Aerosol Med Pulm Drug Deliv. 2018;31(4):221–236.
  • Buttini F, Balducci AG, Colombo G, et al. Dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy. Int J Pharm. 2018 Sep 5 548(1):182–191.
  • Buttini F, Brambilla G, Copelli D, et al. Effect of flow rate on in vitro aerodynamic performance of NEXThaler(®) in comparison with Diskus(®) and Turbohaler(®) dry powder inhalers. J Aerosol Med Pulm Drug Deliv. 2016;29(2):167–178.
  • Cooper A, Parker J, Berry M, et al. Wixela Inhub: dosing performance in vitro and inhaled flow rates in healthy subjects and patients compared with Advair Diskus. J Aerosol Med Pulm Drug Deliv. 2020;33(6): 323–341.
  • Tay JYS, Liew CV, Heng PWS. Dissolution of fine particle fraction from truncated Anderson cascade impactor with an enhancer cell. Int J Pharm. 2018;545(1–2):45–50.
  • Shur J, Saluja B, Lee S, et al. Effect of device design and formulation on the in vitro comparability for multi-unit dose dry powder inhalers. AAPS J. 2015;17(5):1105–1116.
  • Sahakijpijarn S, Moon C, Ma X, et al. Using thin film freezing to minimize excipients in inhalable tacrolimus dry powder formulations. Int J Pharm. 2020;586:119490.
  • Ziffels S, Bemelmans NL, Durham PG, et al. In vitro dry powder inhaler formulation performance considerations. J Control Release. 2015;199:45–52.
  • Dechraksa J, Suwandecha T, Maliwan K, et al. The comparison of fluid dynamics parameters in an Andersen cascade impactor equipped with and without a preseparator. AAPS Pharmscitech. 2014;15(3):792–801.
  • Dolovich MB, Kuttler A, Dimke TJ, et al. Biophysical model to predict lung delivery from a dual bronchodilator dry-powder inhaler. Int J Pharm X. 2019;1:100018.
  • Srichana T, Martin GP, Marriott C. Dry powder inhalers: the influence of device resistance and powder formulation on drug and lactose deposition in vitro. Eur J Pharm Sci. 1998;7(1):73–80.
  • Pohlmann G, Hohlfeld JM, Haidl P, et al. Assessment of the power required for optimal use of current inhalation devices. J Aerosol Med Pulm Drug Deliv. 2018;31(6):339–346.
  • Behara SR, Larson I, Kippax P, et al. Insight into pressure drop dependent efficiencies of dry powder inhalers. Eur J Pharm Sci. 2012;46(3):142–148.
  • Tuley R, Shrimpton J, Jones MD, et al. Experimental observations of dry powder inhaler dose fluidisation. Int J Pharm. 2008;358(1–2): 238–247.
  • Taki M, Marriott C, Zeng XM, et al. Aerodynamic deposition of combination dry powder inhaler formulations in vitro: a comparison of three impactors. Int J Pharm. 2010;388(1): 40–51.
  • Shur J, Saluja B, Lee S, et al. Effect of device design and formulation on the in vitro comparability for multi-unit dose dry powder inhalers. AAPS J. 2015;17(5):1105–1116.
  • Weers J, 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.
  • Hira D, Koide H, Nakamura S, et al. Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices. PloS One. 2018;13(2):e0193082.
  • Suwandecha T, Wongpoowarak W, Srichana T. Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance. Pharm Dev Technol. 2016;21(1):54–60.
  • Suwandecha T, Wongpoowarak W, Maliwan K, et al. Effect of turbulent kinetic energy on dry powder inhaler performance. Powder Technol. 2014;267:381–391.
  • 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):1–11.
  • Maruyama S, Ando S, Yonemochi E. Application of void forming index (VFI): detection of the effect of physical properties of dry powder inhaler formulations on powder cohesion. Int J Pharm. 2020;588:119766.
  • Zhou QT, Tong Z, Tang P, et al. Effect of device design on the aerosolization of a carrier-based dry powder inhaler—a case study on Aerolizer® Foradile®. AAPS J. 2013;15:511–522.
  • Yule AJ, Cox NW, Chigier NA. Particle size analysis. Measurement of particle size in sprays by the automated analysis of spark photographs. London:Heyden;1978. p. 61–73.
  • Adrian RJ, Westerweel J. Particle image velocimetry. New York: Cambridge University Press; 2011.
  • Raffel M, Willert CE, Kompenhans J, et al. Particle image velocimetry: a practical guide. Switzerland: Springer; 1998.
  • Soria J. An investigation of the near wake of a circular cylinder using a video-based digital cross-correlation particle image velocimetry technique. Exp Therm Fluid Sci. 1996;12:221–233.
  • Soria J. Digital particle image velocimetry. In: Rastogi P, editor. Digital optical measurement techniques and applications. United States of America: Artech House Publishers. 2015. p. 347–375.
  • Han R, Papadopoulos G, Greenspan BJ. Flow field measurement inside the mouthpiece of the Spiros inhaler using particle image velocimetry. Aerosol Sci Technol. 2002;36:329–341.
  • Ngoc NTQ, Chang L, Jia X, et al. Experimental investigation of design parameters on dry powder inhaler performance. Int J Pharm. 2013;457:92–100.
  • Kou X, Wereley ST, Heng PWS, et al. Powder dispersion mechanisms within a dry powder inhaler using microscale particle image velocimetry. Int J Pharm. 2016;514:445–455.
  • Voss A, Finlay WH. Deagglomeration of dry powder pharmaceutical aerosols. Int J Pharm. 2002;248:39–50.
  • Wang Z, Lange CF, Finlay WH. Use of an impinging jet for dispersion of dry powder inhalation aerosols. Int J Pharm. 2004;275:123–131.
  • Pasquali I, Merusi C, Brambilla G, et al. Optical diagnostics study of air flow and powder fluidisation in Nexthaler® - Part I: studies with lactose placebo formulation. Int J Pharm. 2015;496:780–791.
  • Elserfy K, Kourmatzis A, Chan HK, et al. Effect of an upstream grid on the fluidization of pharmaceutical carrier powders. Int J Pharm. 2020;578:119079.
  • Singh G, Lowe A, Azeem A, et al. Effect of inflow conditioning for dry powder inhalers. Int J Pharm. 2021;608:121085.
  • Inthavong K. From indoor exposure to inhaled particle deposition: a multiphase journey of inhaled particles. Exp Comput Multiph Flow. 2020;2(2):59–78.
  • Inthavong K, Das P, Singh N, et al. In silico approaches to respiratory nasal flows: a review. J Biomech. 2019;97:109434.
  • Menter FR. Two-equation eddy-viscosity turbulence models for engineering applications. AIAA J. 1994;32(8):1598–1605.
  • Menter FR . Stress-blended eddy simulation (SBES)—a new paradigm in hybrid RANS-LES modeling. In: Hoarau Y, Peng SH, and Schwamborn D, editors. Progress in hybrid RANS-LES modelling. symposium on hybrid RANS-LES methods. Switzerland: Springer; 2016. p. 27–37.
  • Van Strien J, Shrestha K, Gabriel S, et al. Pressure distribution and flow dynamics in a nasal airway using a scale resolving simulation. Phys Fluids. 2021;33(1):011907.
  • Tabe R, Rafee R, Valipour MS, et al. Investigation of airflow at different activity conditions in a realistic model of human upper respiratory tract. Comput Methods Biomech Biomed Engin. 2021;24(2):173–187.
  • Menter FR, Langtry R, Völker S, et al. Transition modelling for general purpose CFD codes. In: Rodi W, Mulas Meditors. Engineering turbulence modelling and experiments 6. Amsterdam: Elsevier Science B.V.; 2005. p. 31–48.
  • Sommerfeld M, Cui Y, Schmalfuß S. Potential and constraints for the application of CFD combined with Lagrangian particle tracking to dry powder inhalers. Eur J Pharm Sci. 2019;128:299–324.
  • Feng Y, Zhao J, Kleinstreuer C, et al. An in silico inter-subject variability study of extra-thoracic morphology effects on inhaled particle transport and deposition. J Aerosol Sci. 2018;123:185–207.
  • Huang F, Zhu Q, Zhou X, et al. Role of CFD based in silico modelling in establishing an in vitro-in vivo correlation of aerosol deposition in the respiratory tract. Adv Drug Deliv. 2021;170:369–385.
  • Kannan RR, Przekwas A, Singh N, et al. Pharmaceutical aerosols deposition patterns from a dry powder inhaler: Euler Lagrangian prediction and validation. Med Eng Phys. 2017;42:35–47.
  • Longest PW, Holbrook LT. In silico models of aerosol delivery to the respiratory tract—development and applications. Adv Drug Deliv. 2012;64(4):296–311.
  • Longest PW, Tian G, Khajeh-Hosseini-Dalasm N, et al. Validating whole-airway CFD predictions of DPI aerosol deposition at multiple flow rates. J Aerosol Med Pulm Drug Deliv. 2016;29(6):461–481.
  • Longest PW, Tian G, Walenga RL, et al. 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(6):1670–1688.
  • Milenkovic J, Alexopoulos AH, Kiparissides C. Flow and particle deposition in the Turbuhaler: a CFD simulation. Int J Pharm. 2013;448(1):205–213.
  • Ruzycki CA, Javaheri E, Finlay WH. The use of computational fluid dynamics in inhaler design. Expert Opin Drug Deliv. 2013;10(3):307–323.
  • Yousefi M, Inthavong K, Tu J. Effect of pressurized metered dose inhaler spray characteristics and particle size distribution on drug delivery efficiency. J Aerosol Med Pulm Drug Deliv. 2017;30(5):359–372.
  • Yousefi M, Pourmehran O, Gorji-Bandpy M, et al. CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization. Biomech Model Mechanobiol. 2017;16(6):2035–2050.
  • Cui Y, Sommerfeld M. Forces on micron-sized particles randomly distributed on the surface of larger particles and possibility of detachment. Int J Multiph Flow. 2015;72:39–52.
  • Cheng Y, Fu C, Yazzie D, et al. Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica. J Aerosol Med. 2001;14(2):255–266.
  • DeHaan WH, Finlay WH. In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices. J Aerosol Med. 2001;14(3):361–367.
  • Pich J. Theory of gravitational deposition of particles from laminar flows in channels. J Aerosol Sci. 1972;3(5):351–361.
  • Bates AJ, Schuh A, McConnell K, et al. A novel method to generate dynamic boundary conditions for airway CFD by mapping upper airway movement with non‐rigid registration of dynamic and static MRI. Int J Numer Method Biomed Eng. 2018;34(12):e3144.
  • Ferron GA, Oberdörster G, Henneberg R. Estimation of the deposition of aerosolized drugs in the human respiratory tract due to hygroscopic growth. J Aerosol Med. 1989;2(3):271–284.
  • Hindle M, 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(9):1800–1811.
  • Tian G, Longest PW, Li X, et al. Targeting aerosol deposition to and within the lung airways using excipient enhanced growth. J Aerosol Med Pulm Drug Deliv. 2013;26(5):248–265.
  • Inthavong K. A unifying correlation for laminar particle deposition in 90-degree pipe bends. Powder Technol. 2019;345:99–110.
  • Lin CL, Tawhai MH, McLennan G, et al. Characteristics of the turbulent laryngeal jet and its effect on airflow in the human intra-thoracic airways. Respir Physiol Neurobiol. 2007;157(2):295–309.
  • Corcoran TE, Chigier N. Characterization of the laryngeal jet using phase Doppler interferometry. J Aerosol Med. 2000;13(2):125–137.
  • Inthavong K, Choi LT, Tu J, et al. Micron particle deposition in a tracheobronchial airway model under different breathing conditions. Med Eng Phys. 2010;32(10):1198–1212.
  • Chen X, Feng Y, Zhong W, et al. Numerical investigation of particle deposition in a triple bifurcation airway due to gravitational sedimentation and inertial impaction. Powder Technol. 2018;323:284–293.
  • Zhu K, Ng WK, Shen S, et al. Design of a device for simultaneous particle size and electrostatic charge measurement of inhalation drugs. Pharm Res. 2008;25(11):2488–2496.
  • Sun Y, Cui Z, Sun Y, et al. Exploring the potential influence of drug charge on downstream deposition behaviour of DPI powders. Int J Pharm. 2020;588:119798.
  • Chaugule V, Gomes Dos Reis L, Fletcher DF, et al. Unravelling DPI aerosol performance using in-vitro deposition and particle image velocimetry. In: Dalby RN, Peart J, and Suman JD, et al., editor. RDD Online, 2021 May 4–7; Richmond, VA. USA: Aptar Pharma; 2021. 203–208.
  • Chaugule V, Dos Reis LG, Fletcher DF, et al. Particle image velocimetry measurements of a dry powder inhaler flow. In: 14th international symposium on particle image velocimetry, 2021 Aug 1–4. Chicago, IL. Illinois: Illinois Institute of Technology; 2021.
  • Schenk H, Wagner M, Grahmann J, et al. Advances in MOEMS technologies for high quality imaging systems. In: SPIE Advanced Lithography. San Jose, California. USA: Society of Photo-Optical Instrumentation Engineers; 2018. p. 1058703.
  • Wise FW, Wright LG, Sidorenko P, et al. Several new directions for ultrafast fiber lasers. Opt Express. 2018;26(8):9432–9463.
  • Soria J. Three-component three-dimensional (3C-3D) fluid flow velocimetry for flow turbulence investigations. Proceedings of the 21st Australasian Fluid Mechanics Conference Australasian Fluid Mechanics Society; 2018 Dec 10-13; Adelaide, Australia. Australia: Australasian Fluid Mechanics Society; 2018.
  • Chiang L, Lu B, Castillo I. Big data analytics in chemical engineering. Annu Rev Chem Biomol Eng. 2017;8(1):63–85.
  • Reinhardt IC, Oliveira DJC, Ring DDT. Current perspectives on the development of industry 4.0 in the pharmaceutical sector. J Ind Inf Integr. 2020;18:100131.
  • Ioppolo G, Vazquez F, Hennerici MG, et al. Medicine 4.0: new technologies as tools for a society 5.0. J Clin Med. 2020;9(7):2198.
  • Wolf B, Scholze C. Medicine 4.0. Curr Dir Biomed Eng. 2017;3(2):183–186.
  • Björnsson B, Borrebaeck C, Elander N, et al. Digital twins to personalize medicine. Genome Med. 2020;12:4.
  • Coorey G, Figtree GA, Fletcher DF, et al. The health digital twin: advancing precision cardiovascular medicine. Nat Rev Cardiol. 2021;18:803–804.
  • Mishra S, Dash A, Mishra BK. Chapter 9 - an insight of internet of things applications in pharmaceutical domain. In: Balas VE, Solanki VK, Kumar R, editors. Emergence of pharmaceutical industry growth with industrial IoT approach. Cambridge: Academic Press; 2020. p. 245–273.
  • Kalaiselvi G. A comprehensive study on healthcare applications using IoT. Int J Eng Invent. 2018;1:41–45.
  • Pant P, Doshi R, Bahl P, et al. Deep learning for reduced order modelling and efficient temporal evolution of fluid simulations. Phys Fluids. 2021;33(10):107101.

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