Pharmaceutical Research

, 26:2639 | Cite as

The Influence of Flow Rate on the Aerosol Deposition Profile and Electrostatic Charge of Single and Combination Metered Dose Inhalers

  • Susan Hoe
  • Daniela Traini
  • Hak-Kim Chan
  • Paul M. Young
Research Paper



The capability of the electrostatic next generation impactor (eNGI) has been investigated as a tool capable of measuring the electrostatic charge of single (Flixotide™; containing fluticasone propionate (FP)) and combination (Seretide™; FP and salmeterol xinafoate (SX)) pressurised metered dose inhalers (pMDIs) at different flow rates.


Aerosol mass distributions were investigated at 30, 60 and 90 l.min−1 and simultaneous charge measurements recorded.


Analysis of the mass distribution data indicated a flow dependent relationship, where the aerosol performance (aerodynamic diameter <5 μm) of FP significantly increased between 30 l.min−1 and 60 l.min−1 for both formulations. No significant increase in SX was observed for Seretide with increased flow rate. Analysis of the charge distribution indicated both formulations to primarily charge negatively with a concurrent increase in charge with increased flow rate. Interestingly, the charge-tomass ratio remained relatively constant between 30 l.min−1 and 60 l.min−1 and increased at 90 l.min−1, indicating that charging was majorly influenced at the highest flow rate.


This study has shown how the eNGI could be used as a simple Pharmacopeia based methodology for the evaluation of mass and charge profiles of single and combination pMDIs at a series of flow rates.


electrostatic NGI electrostatics eNGI pMDI flow rate inhalation 


  1. 1.
    Pritchard JN. The influence of lung deposition on clinical response 1. J Aerosol Med. 2001;14:S19–26.CrossRefPubMedGoogle Scholar
  2. 2.
    Bennett WD, Brown JS, Zeman KL, Hu SC, Scheuch G, Sommerer K. Targeting delivery of aerosols to different lung regions. J Aerosol Med. 2002;15(2):179–88.CrossRefPubMedGoogle Scholar
  3. 3.
    Chapter < 601 > (2008),. United States Pharmacopeia 31—National Formulary 26, : United States Pharmacopeial Convention Inc.; 2008.Google Scholar
  4. 4.
    Section 2.9.18—appendix XII C. Consistency of Formulated Preparations for inhalation. British Pharmacopoeia 2009.Google Scholar
  5. 5.
    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(2):215–26.CrossRefPubMedGoogle Scholar
  6. 6.
    Terzano C, Mannino F. Aerosol characterization of three corticosteroid metered dose inhalers with volumatic holding chambers and metered dose inhalers alone at two inspiratory flow rates. J Aerosol Med. 1999;12(4):249–54.CrossRefPubMedGoogle Scholar
  7. 7.
    Mitchell JP, Nagel MW. Time-of-flight aerodynamic particle size analyzers: their use and limitations for the evaluation of medical aerosols. J Aerosol Med. 1999;12(4):217–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Mitchell JP, Nagel MW, Cheng YS. Use of the aerosizer (R) aerodynamic particle size analyzer to characterize aerosols from pressurized metered-dose inhalers (pMDIs) for medication delivery. J Aerosol Sci. 1999;30(4):467–77.CrossRefGoogle Scholar
  9. 9.
    Smith KJ, Chan HK, Brown KF. Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers. J Aerosol Med. 1998;11(4):231–45.CrossRefPubMedGoogle Scholar
  10. 10.
    Feddah MR, Brown KF, Gipps EM, Davies NM. In-vitro characterisation of metered dose inhaler versus dry powder inhaler glucocorticoid products: influence of inspiratory flow rates. J Pharm Pharm Sci. 2000;3(3):318–24.PubMedGoogle Scholar
  11. 11.
    Bailey AG. The inhalation and deposition of charged particles within the human lung. J Electrostat. 1997;42(1–2):25–32.CrossRefGoogle Scholar
  12. 12.
    Balachandran W, Machowski W, Gaura E, Hudson C. Control of drug aerosol in human airways using electrostatic forces. J Electrostat. 1997;40–1:579–84.CrossRefGoogle Scholar
  13. 13.
    Koolpiruck D, Prakoonwit S, Balachandran W. Numerical modeling of inhaled charged aerosol deposition in human airways. Ieee T Ind Appl. 2004;40(5):1239–48.CrossRefGoogle Scholar
  14. 14.
    Ali M, Mazumder MK, Martonen TB. Measurements of electrodynamic effects on the deposition of MDI and DPI aerosols in a replica cast of human oral-pharyngeal-laryngeal airways. J Aerosol Med Pulm D. 2009;22(1):35–44.Google Scholar
  15. 15.
    Ali M, Reddy RN, Mazumder MK. Electrostatic charge effect on respirable aerosol particle deposition in a cadaver based throat cast replica. J Electrostat [Article]. 2008;66(7–8):401–6.CrossRefGoogle Scholar
  16. 16.
    Melandri C, Tarroni G, Prodi V, Dezaiacomo T, Formignani M, Lombardi CC. Deposition of charged-particles in the human airways. J Aerosol Sci. 1983;14(5):657–69.CrossRefGoogle Scholar
  17. 17.
    Kwok PCL, Collins R, Chan HK. Effect of spacers on the electrostatic charge properties of metered dose inhaler aerosols. J Aerosol Sci. 2006;37(12):1671–82.CrossRefGoogle Scholar
  18. 18.
    Lipworth BJ, Lee DKC, Anhoj J, Bisgaard H. Effect of plastic spacer handling on salbutamol lung deposition in asthmatic children. Brit J Clin Pharmaco. 2002;54(5):544–7.CrossRefGoogle Scholar
  19. 19.
    Mitchell JP, Coppolo DP, Nagel MW. Electrostatics and inhaled medications: influence on delivery via pressurized metered-dose inhalers and add-on devices. Respir Care. 2007;52(3):283–300.PubMedGoogle Scholar
  20. 20.
    Newman SP. Spacer devices for metered dose inhalers. Clin Pharmacokinet. 2004;43(6):349–60.CrossRefPubMedGoogle Scholar
  21. 21.
    Keskinen J, Pietarinen K, Lehtimaki M. Electrical low-pressure impactor. J Aerosol Sci. 1992;23(4):353–60.CrossRefGoogle Scholar
  22. 22.
    Glover W, Chan HK. Electrostatic charge characterization of pharmaceutical aerosols using electrical low-pressure impaction (ELPI). J Aerosol Sci. 2004;35(6):755–64.CrossRefGoogle Scholar
  23. 23.
    Kwok PCL, Glover W, Chan HK. Electrostatic charge characteristics of aerosols produced from metered dose inhalers. J Pharm Sci-Us. 2005;94(12):2789–99.CrossRefGoogle Scholar
  24. 24.
    Kotian R, Peart J, Bryner J, Byron PR. Calibration of the modified electrical low-pressure impactor (ELPI) for use with pressurized pharmaceutical aerosols. J Aerosol Med Pulm D. 2009;22(1):55–65.Google Scholar
  25. 25.
    Electrical Low Pressure Impactor product specifications. Osuusmyllynkatu 13, FIN-33700 Tampere, Finland : Dekati Ltd.; 2009.Google Scholar
  26. 26.
    Saini D, Biris AS, Srirama PK, Mazumder MK. Particle size and charge distribution analysis of pharmaceutical aerosols generated by inhalers. Pharm Dev Technol. 2007;12(1):35–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Philip VA, Mehta RC, Mazumder MK, DeLuca PP. Effect of surface treatment on the respirable fractions of PLGA microspheres formulated for dry powder inhalers. Int J Pharm. 1997;151(2):165–74.CrossRefGoogle Scholar
  28. 28.
    Yurteri CU, Mazumder MK, Grable N, Ahuja G, Trigwell S, Biris AS, et al. Electrostatic effects on dispersion, transport, and deposition of fine pharmaceutical powders: development of an experimental method for quantitative analysis. Part Sci Technol. 2002;20(1):59–79.CrossRefGoogle Scholar
  29. 29.
    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.CrossRefPubMedGoogle Scholar
  30. 30.
    Marple VA, Roberts DL, Romay FJ, Miller NC, Truman KG, Van Oort M, et al. Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part I: Design. J Aerosol Med. 2003;16(3):283–99.CrossRefPubMedGoogle Scholar
  31. 31.
    Hoe S, Young PM, Chan HK, Traini D. Introduction of the electrical next generation impactor (eNGI) and investigation of its capabilities for the study of pressurized metered dose inhalers. Pharm Res. 2009;26(2):431–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Hoe S, Traini D, Chan H-K, Young PM. Measuring charge and mass distributions in dry powder inhalers using the electrical Next Generation Impactor (eNGI). Eur J Pharm Sci. 2009;38(2):88–94.CrossRefPubMedGoogle Scholar
  33. 33.
    Hoe S, Traini D, Chan HK, Young PM. The electrical next generation impactor. Inhalation. 2009:in press.Google Scholar
  34. 34.
    Murnane D, Martin GP, Marriott C. Validation of a reverse-phase high performance liquid chromatographic method for concurrent assay of a weak base (salmeterol xinafoate) and a pharmacologically active steroid (fluticasone propionate). J Pharm Biomed Anal. 2006;40(5):1149–54.CrossRefPubMedGoogle Scholar
  35. 35.
    Young PM, Price R, Jones S, Billings M-P. Investigation into drug and excipient interaction in dry powder inhaler combination products. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, editors. Respiratory drug delivery IX; California. USA: Davis Healthcare International Publishing; 2004. p. 749–51.Google Scholar
  36. 36.
    Michael Y, Chowdhry BZ, Ashurst IC, Snowden MJ, Davies-Cutting C, Gray S. The physico-chemical properties of salmeterol and fluticasone propionate in different solvent environments. Int J Pharm. 2000;200(2):279–88.CrossRefPubMedGoogle Scholar
  37. 37.
    Michael Y, Snowden MJ, Chowdhry BZ, Ashurst IC, Davies-Cutting CJ, Riley T. Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system. Int J Pharm. 2001;221(1–2):165–74.CrossRefPubMedGoogle Scholar
  38. 38.
    Bailey AG, Hashish AH, Williams TJ. Drug delivery by inhalation of charged particles. J Electrostat. 1997;44(1–2):3–10.Google Scholar
  39. 39.
    Ali FS, Ali MA, Ali RA. Inculet, II. Minority charge separation in falling particles with bipolar charge. J Electrostat. 1998;45(2):139–55.CrossRefGoogle Scholar
  40. 40.
    Lacks DJ, Levandovsky A. Effect of particle size distribution on the polarity of triboelectric charging in granular insulator systems. J Electrostat. 2007;65(2):107–12.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Susan Hoe
    • 1
  • Daniela Traini
    • 1
  • Hak-Kim Chan
    • 1
  • Paul M. Young
    • 1
  1. 1.Advanced Drug Delivery Group, Faculty of PharmacyUniversity of SydneySydneyAustralia

Personalised recommendations