AAPS PharmSciTech

, Volume 9, Issue 1, pp 112–115 | Cite as

Estimating the Number of Droplets and Drug Particles Emitted from MDIs

  • Stephen W. Stein
Research Article


The objective of this paper is to assess the number of drug particles or droplets contained in metered dose inhaler (MDI) aerosols. Equations were developed to estimate this. The number of drug particles was estimated to be as high as about 300 million for QVAR® solution MDIs and as low as 670,000 for Beclovent™ MDIs. The number of particles in MDI aerosols was shown to be highly dependent on the mass median aerodynamic diameter (MMAD) and geometric standard deviation, and to a lesser extent the total mass of the aerosol. It was demonstrated that when the number of particles are calculated assuming that the aerosol is monodisperse and using the MMAD as the particle size, the number of particles are significantly underestimated. The number of droplets atomized from HFA-134a MDIs was estimated to range from about 220 million to about 1.1 billion droplets per actuation. For solution MDIs, each of the atomized droplets contains drug and thus the number of drug particles is the same as the number of atomized droplets. However, for suspension MDI formulations many of the droplets do not contain any micronized drug particles and the number of drug particles is much lower than the number of atomized droplets.

Key words

metered dose inhaler number of particles size distribution 


  1. 1.
    B. J. Meakin, D. A. Lewis, D. Ganderton, and G. Brambilla. Countering challenges posed by mimicry of CFC performance using HFA systems. In R. N. Dalby, P. R. Byron, S. J. Farr, and J. Peart (eds.), Respiratory Drug Delivery-VII, Serentec, Raleigh, pp. 99–107 (2000).Google Scholar
  2. 2.
    S. W. Stein and P. B. Myrdal. A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J. Pharm. Sci. 93:2158–2175 (2004).CrossRefGoogle Scholar
  3. 3.
    I. Gonda. Development of a systematic theory of suspension inhalation aerosols-I. A framework to study the effects of aggregation on the aerodynamic behaviour of drug particles. Int. J. Pharm. 27:99–116 (1985).CrossRefGoogle Scholar
  4. 4.
    P. H. Howarth. Why particle size should affect clinical response to inhaled therapy. J. Aerosol. Med. 14:S27–S34 (2001).CrossRefGoogle Scholar
  5. 5.
    L. Harrison, C. Leach, J. Machacek, J. Vanden Burgt, and J. Vogel. Beneficial effects with reduced particle size and CFC-free extrafine aerosol steroid on lung deposition, absorption, efficacy and safety. Am. J. Respir. Crit. Care. Med. 155:A666 (1997).Google Scholar
  6. 6.
    A. J. Hickey, T. B. Martonen, Y. Yang. Theoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols. Pharmaceutica Acta Helvetiae. 71:185–190 (1996).CrossRefGoogle Scholar
  7. 7.
    C. A. Malton, G. W. Hallworth, J. M. Padfield. The association and particle size distribution of drug and surfactant discharged from a metered-dose inhalation aerosol. J. Pharm. Pharmacol. 34:65P (1982).Google Scholar
  8. 8.
    L. McKenzie, and M. J. Oliver. Evaluation of the particle formation process after actuation of solution MDIs. J Aerosol. Med. 13:59 (2000).CrossRefGoogle Scholar
  9. 9.
    T. Hatch, and S. P. Choate. Statistical description of the size properties of non-uniform particulate substances. J. Franklin Inst. 207:369 (1929).CrossRefGoogle Scholar
  10. 10.
    W. C. HindsAerosol technology: properties, behavior, and measurement of airborne particles, Wiley, New York, pp. 91–95 (1982).Google Scholar
  11. 11.
    S. W. Stein. Size distribution measurements of metered dose inhalers using Andersen Mark II cascade impactors. Int. J. Pharm. 186:43–52 (1999).CrossRefGoogle Scholar
  12. 12.
    J. P. Mitchell, M. W. Nagel, K. J. Wiersema, C. C. Doyle. Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: comparison of Andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 aerodynamic particle sizer aerosol spectrometerAAPS PharmSciTech [] 4(4):54 (2003).
  13. 13.
    USP 26-NF 21. Chapter 601-Physical tests and determinations: aerosols. United States Pharmacopeia. Rockville: United States Pharmacopeial Convention. 2105–2123 (2003).Google Scholar
  14. 14.
    S. W. Stein, B. J. Gabrio, and T. J. Beck. Evaluation of a new aerodynamic particle sizer spectrometer for MDI size distribution measurements. In R. N. Dalby, P. R. Byron, S. J. Farr, and J. Peart (eds.), Respiratory Drug Delivery-VII, Serentec, Raleigh, pp. 283–286 (2000).Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  1. 1.Early Pharmaceutics and Technology Department3M Drug Delivery SystemsSt. PaulUSA

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