The AAPS Journal

, 20:84 | Cite as

Effect of Inhalation Flow Rate on Mass-Based Plume Geometry of Commercially Available Suspension pMDIs

  • Daniel F. Moraga-Espinoza
  • Eli Eshaghian
  • Albert Shaver
  • Hugh D. C. SmythEmail author
Research Article


Although high-speed laser imaging is the current standard to characterize the plume angle of suspension-based pressurized metered dose inhalers (pMDIs), this method is limited by the inability to identify the drug content in a droplet and simulate inhalation flow. The Plume Induction Port Evaluator (PIPE) is a modified induction port for cascade impactors that allows for the calculation of the angle of a plume based on direct drug mass quantification rather than indirect droplet illumination under airflow conditions. The objective of this study was to investigate the use of the PIPE apparatus to evaluate the effect of airflow on the Mass Median Plume Angle (MMPA) of commercially available suspension-based pMDIs (Ventolin® HFA, ProAir® HFA, and Proventil® HFA). Deposition patterns within PIPE were log-normally distributed allowing for the calculation of the MMPA for the three suspension products. Mass-based plume angles were significantly smaller (narrower angle) when inhalation airflow was used compared to no flow conditions (reduction of MMPA was 8, 16, and 13% for Ventolin® HFA, ProAir® HFA, and Proventil® HFA, respectively). Additionally, new parameters for characterizing plume geometry were calculated (MMPA ex-actuator and plume orientation). Mass-based plume angles of the suspension-based pMDI formulations were highly reproducible and demonstrated the effect of inhalation flow rate. These results suggest that plume geometry tests should be evaluated under flow conditions which is not possible using current methodologies.

Graphical Abstract


mass median plume angle plume geometry albuterol sulfate plume induction port evaluator high-speed laser imaging 



High-speed laser imaging


Mass Median Plume Angle


Plume Induction Port Evaluator



Daniel Moraga-Espinoza would like to thank CONICYT-Becas Chile for the scholarship to pursue his doctoral studies.

Compliance with Ethical Standards

Conflict of Interest

The author (HDCS) of this paper consults for and has equity ownership in Respira Therapeutics and Nob Hill Therapeutics on inhaled product development. The terms of this arrangement have been reviewed and approved by the University of Texas at Austin in accordance with its policy on objectivity in research.


  1. 1.
    Chen Y, Young PM, Murphy S, Fletcher DF, Long E, Lewis D, 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)782–9.Google Scholar
  2. 2.
    Smyth H, Hickey A, Brace G, Barbour T, Gallion J, Grove J. Spray pattern analysis for metered dose inhalers I: orifice size, particle size, and droplet motion correlations. Drug Dev Ind Pharm. 2006;32(9):1033–41.CrossRefPubMedGoogle Scholar
  3. 3.
    ITFG/IPACR. Recommendations to the Food and Drug Administration: metered dose inhaler tests and methods in the chemistry, manufacturing, and controls draft guidances for metered dose inhalers and dry powder inhalers. Drug Inf J. 2002;36(3):549–56.CrossRefGoogle Scholar
  4. 4.
    Berrocal E, Kristensson E, Richter M, Linne M, Aldén M. Application of structured illumination for multiple scattering suppression in planar laser imaging of dense sprays. Opt Express. 2008;16(22):17870–81.CrossRefPubMedGoogle Scholar
  5. 5.
    Linne M. Imaging in the optically dense regions of a spray: a review of developing techniques. Prog Energy Combust Sci. 2013;39(5):403–40.CrossRefGoogle Scholar
  6. 6.
    Stein SW, Sheth P, Myrdal PB. A model for predicting size distributions delivered from pMDIs with suspended drug. Int J Pharm. 2012;422(1–2):101–15.CrossRefPubMedGoogle Scholar
  7. 7.
    Stein SW. Estimating the number of droplets and drug particles emitted from MDIs. AAPS PharmSciTech. 2008;9(1):112–5.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Moraga-Espinoza D, Eshaghian E, Smyth HD. Mass median plume angle: a novel approach to characterize plume geometry in solution based pMDIs. Int J Pharm. 2018;543:376–85.CrossRefPubMedGoogle Scholar
  9. 9.
    O’Shaughnessy PT, Raabe OG. A comparison of cascade impactor data reduction methods. Aerosol Sci Technol. 2003;37(2):187–200.CrossRefGoogle Scholar
  10. 10.
    Longest PW, Hindle M, Choudhuri SD, 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(7):572–91.CrossRefGoogle Scholar
  11. 11.
    Liu X, Doub WH, Guo C. Evaluation of metered dose inhaler spray velocities using phase Doppler anemometry (PDA). Int J Pharm. 2012;423(2):235–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82.CrossRefPubMedGoogle Scholar
  13. 13.
    McCabe JC, Koppenhagen F, Blair J, Zeng X-M. ProAir® HFA delivers warmer, lower-impact, longer-duration plumes containing higher fine particle dose than Ventolin® HFA. J Aerosol Med Pulm Drug Deliv. 2012;25(2):104–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Cheng Y, Fu C, Yazzie D, Zhou Y. Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica. J Aerosol Med. 2001;14(2):255–66.CrossRefPubMedGoogle Scholar
  15. 15.
    Doub WH, Shah V, Limb S, Guo C, Liu X, Ngo D. Developing an in vitro understanding of patient experience with hydrofluoroalkane-metered dose inhalers. J Pharm Sci. 2014;103(11):3648–56.CrossRefPubMedGoogle Scholar
  16. 16.
    Ohrn T, Senser DW, Lefebvre AH. Geometric effects on spray cone angle for plain-orifice atomizers. Atomization Sprays. 1991;1(3):253–68.Google Scholar
  17. 17.
    Brambilla G, Ganderton D, Garzia R, Lewis D, Meakin B, Ventura P. Modulation of aerosol clouds produced by pressurised inhalation aerosols. Int J Pharm. 1999;186(1):53–61.CrossRefPubMedGoogle Scholar
  18. 18.
    Gabrio BJ, Stein SW, Velasquez DJ. A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers. Int J Pharm. 1999;186(1):3–12.CrossRefPubMedGoogle Scholar
  19. 19.
    Kleinstreuer C, Shi H, Zhang Z. Computational analyses of a pressurized metered dose inhaler and a new drug–aerosol targeting methodology. J Aerosol Med. 2007;20(3):294–309.CrossRefPubMedGoogle Scholar
  20. 20.
    Longest PW, Hindle M, Choudhuri SD, Byron PR. Numerical simulations of capillary aerosol generation: CFD model development and comparisons with experimental data. Aerosol Sci Technol. 2007;41(10):952–73.CrossRefGoogle Scholar
  21. 21.
    Versteeg H, Hargrave G, Harrington L, Shrubb I, Hodson D, editors. The use of computational fluid dynamics (CFD) to predict pMDI air flows and aerosol plume formation. Respiratory Drug Delivery. 2000;1:257–64.Google Scholar
  22. 22.
    Bonam M, Christopher D, Cipolla D, Donovan B, Goodwin D, Holmes S, et al. Minimizing variability of cascade impaction measurements in inhalers and nebulizers. AAPS PharmSciTech. 2008;9(2):404–13.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Sheth P, Stein SW, Myrdal PB. The influence of initial atomized droplet size on residual particle size from pressurized metered dose inhalers. Int J Pharm. 2013;455(1–2):57–65.CrossRefPubMedGoogle Scholar
  24. 24.
    Ehtezazi T, Saleem I, Shrubb I, Allanson D, Jenkinson I, O’Callaghan C. The interaction between the oropharyngeal geometry and aerosols via pressurised metered dose inhalers. Pharm Res. 2010;27(1):175–86.CrossRefPubMedGoogle Scholar
  25. 25.
    FDA. Draft guidance on budesonide; formoterol fumarate dihydrate. Silver Spring: US Food and Drug Administration; 2015.Google Scholar
  26. 26.
    Delvadia RR, Longest PW, Hindle M, Byron PR. In vitro tests for aerosol deposition. III: effect of inhaler insertion angle on aerosol deposition. J Aerosol Med Pulm Drug Deliv. 2013;26(3):145–56.CrossRefPubMedGoogle Scholar
  27. 27.
    Fadl A, Wang J, Zhang Z, Cheng YS. Effects of MDI spray angle on aerosol penetration efficiency through an oral airway cast. J Aerosol Sci. 2007;38(8):853–64.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Daniel F. Moraga-Espinoza
    • 1
    • 2
    • 3
  • Eli Eshaghian
    • 4
  • Albert Shaver
    • 1
  • Hugh D. C. Smyth
    • 1
    Email author
  1. 1.Division of Molecular Pharmaceutics and Drug Delivery, College of PharmacyThe University of Texas at AustinAustinUSA
  2. 2.Escuela De FarmaciaUniversidad de ValparaísoValparaísoChile
  3. 3.Centro de Investigación Farmacopea ChilenaUniversidad de ValparaísoValparaísoChile
  4. 4.College of Natural SciencesThe University of Texas at AustinAustinUSA

Personalised recommendations