Pharmaceutical Research

, 36:15 | Cite as

Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI)

  • Martin RowlandEmail author
  • Alessandro Cavecchi
  • Frank Thielmann
  • Janusz Kulon
  • Jag Shur
  • Robert Price
Research Paper



To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). Measurements were performed with a purpose built bipolar charge measurement apparatus (bp-NGI) based on an electrostatic precipitator, which was directly connected below Stage 2 of a Next Generation Impactor (NGI).


Five successive shots of the respective MDIs were actuated through the bp-NGI. The whole ISM doses were electrostatically precipitated to determine their negative, positive and net Q/m ratios.


The ISM doses collected in the bp-NGI were shown to be equivalent to those collected in a standard NGI. FP particles, actuated from Flixotide™ and Seretide™ MDIs, exhibited greater quantities of negatively charged particles than positive. However, the Q/m ratios of the positively charged particles were greater in magnitude. SX particles from Serevent™ exhibited a greater quantity of positively charged particles whereas SX aerosol particles from Seretide™ exhibited a greater quantity of negatively charged particles. The Q/m ratio of the negatively charged SX particles in Serevent™ was greater in magnitude than the positively charged particles.


The bp-NGI was used to quantify the bipolar Q/m ratios of aerosol particles collected from the ISMs of commercial MDI products. The positive charge recorded for each of the three MDIs may have been enhanced by the presence of charged ice crystals formed from the propellant during the aerosolisation process.


Bipolar charge bipolar next generation impactor electrostatic charge pressurized metered dose inhaler 



Active pharmaceutical ingredient


Bayonet Neill-Concelman


Bipolar charge analyser


Bipolar next generation impactor


Direct current


Emitted dose


Electrical low pressure impactor


Electrical single particle aerodynamic relaxation time


Fluticasone propionate




High performance liquid chromatography


Impactor stage mass


Next generation impactor


Pressurized metered dose inhaler


Recovered dose


Salmeterol xinafoate


  1. 1.
    Murata S, Izumi T, Ito H. Effect of the moisture content in aerosol on the spray performance of Stmerin ® D hydrofluoroalkane preparations (2). Chem Pharm Bull (Tokyo). 2012;60(5):593–7.CrossRefGoogle Scholar
  2. 2.
    James J, Davies M, Toon R, Jinks P, Roberts CJ. Particulate drug interactions with polymeric and elastomeric valve components in suspension formulations for metered dose inhalers. Int J Pharm. 2009;366(1–2):124–32.CrossRefGoogle Scholar
  3. 3.
    Kwetkus BA. Particle Triboelectrification and its use in the electrostatic separation process. Part Sci Technol. 1998;16(1):55–68.CrossRefGoogle Scholar
  4. 4.
    Lowell J. The role of material transfer in contact electrification. J Phys D. 1977;10:L233–L5.CrossRefGoogle Scholar
  5. 5.
    Matsusaka S, Maruyama H, Matsuyama T, Ghadiri M. Triboelectric charging of powders: a review. Chem Eng Sci. 2010;65(22):5781–807.CrossRefGoogle Scholar
  6. 6.
    Kulphaisal P Peart J, Byron P, editors. (2002) Influence of water on electrical properties in hydrofluoroalkane based metered dose inhalers. Respiratory Drug Delivery VIII; Raleigh, NC: Davis Horwood International.Google Scholar
  7. 7.
    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. Journal of Aerosol Medicine and Pulmonary Drug Delivery. 2009;22(1):35–44.CrossRefGoogle Scholar
  8. 8.
    Keskinen J, Pietarinen K, Lehtimaki M. Electrical low pressure impactor. J Aerosol Sci. 1992;23(4):353–60.CrossRefGoogle Scholar
  9. 9.
    Glover W, Chan H-K. Electrostatic charge characterization of pharmaceutical aerosols using electrical low-pressure impaction (ELPI). J Aerosol Sci. 2004;35(6):755–64.CrossRefGoogle Scholar
  10. 10.
    Kwok P, Glover W, Chan HK. Electrostatic charge characteristics of aerosols produced from metered dose inhalers. J Pharm Sci. 2005;94(12):2789–99.CrossRefGoogle Scholar
  11. 11.
    Hoe S, Young P, Chan H-K, 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.CrossRefGoogle Scholar
  12. 12.
    Hoe S. The influence of flow rate on the aerosol deposition profile and ElectrostaticCharge of single and combination metered dose inhalers. Pharm Res. 2009;26(12):2639–46.CrossRefGoogle Scholar
  13. 13.
    Mizuno A. Electrostatic precipitation. IEEE Trans Dielectr Electr Insul. 2000;7(5):615–24.CrossRefGoogle Scholar
  14. 14.
    O'Leary M, Balachandran W, Rogueda P, Chambers F. The bipolar nature of charge resident on supposedly unipolar aerosols. J Phys Conf Ser. 2008;142:012022.CrossRefGoogle Scholar
  15. 15.
    Kulon J, Balachandran W. The measurement of bipolar charge on aerosols. J Electrost. 2001;51-52(0):552–7.CrossRefGoogle Scholar
  16. 16.
    Yli-Ojanpera J, Ukkonen A, Jarvinen A, Layzell S, Niemela V, Keskinen J. Bipolar charge analyzer (BOLAR): a new aerosol instrument for bipolar charge measurements. J Aerosol Sci. 2014;77:16–30.CrossRefGoogle Scholar
  17. 17.
    Wong J, Lin Y-W, Kwok PCL, Niemela V, Crapper J, Chan H-K. Measuring bipolar charge and mass distributions of powder aerosols by a novel tool (BOLAR). Mol Pharm. 2015;12(9):3433–40.CrossRefGoogle Scholar
  18. 18.
    Wong J, Kwok PCL, Niemela V, Heng D, Crapper J, Chan H-K. Bipolar electrostatic charge and mass distributions of powder aerosols - effects of inhaler design and inhaler material. J Aerosol Sci. 2016;95:104–17.CrossRefGoogle Scholar
  19. 19.
    Leung SSY, Chiow ACM, Ukkonen A, Chan H-K. Applicability of bipolar charge analyzer (BOLAR) in characterizing the bipolar electrostatic charge profile of commercial metered dose inhalers (MDIs). Pharm Res. 2016;33(2):283–91.CrossRefGoogle Scholar
  20. 20.
    Leung SSY, Chiow ACM, Kwok PCL, Ukkonen A, Chan H-K. Effect of spacers on the bipolar electrostatic charge properties of metered dose inhaler aerosols-a case study with Tilade. J Pharm Sci. 2017;106(6):1553–9.CrossRefGoogle Scholar
  21. 21.
    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. Journal of Aerosol Medicine. 2003;16(3):283–99.CrossRefGoogle Scholar
  22. 22.
    Kulon J, Hrabar S, Machowski W, Balachandran W. A bipolar charge measurement system for aerosol characterization. IEEE Trans Ind Appl. 2001;37(2):472–9.CrossRefGoogle Scholar
  23. 23.
    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;40:1149–54.CrossRefGoogle Scholar
  24. 24.
    Chow KT, Zhu K, Tan RBH, Heng PWS. Investigation of electrostatic behavior of a lactose carrier for dry powder inhalers. Pharm Res. 2008;25(12):2822–34.CrossRefGoogle Scholar
  25. 25.
    Peart J, Kulphaisal P, Orban JC. Relevance of electrostatics in respiratory drug delivery. Business Briefing: Pharmagenerics. 2003:1–4.Google Scholar
  26. 26.
    Kwok P, Noakes T, Chan H-K. Effect of moisture on the electrostatic charge properties of metered dose inhaler aerosols. J Aerosol Sci. 2008;39(3):211–26.CrossRefGoogle Scholar
  27. 27.
    Theophilus A, Moore A, Prime D, Rossomanno S, Whitcher B, Chrystyn H. Co-deposition of salmeterol and fluticasone propionate by a combination inhaler. Int J Pharm. 2006;313(1–2):14–22.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pharmaceutical Surface Science Research Group, Department of Pharmacy and PharmacologyUniversity of BathBathUK
  2. 2.Pfizer LtdKentUK
  3. 3.Novartis Pharma AG, Forum 1BaselSwitzerland
  4. 4.Chiesi Farmaceutici S.p.AParmaItaly
  5. 5.Faculty of Computing, Engineering and ScienceUniversity of South WalesPontypriddUK

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