Factors Influencing Aerodynamic Particle Size Distribution of Suspension Pressurized Metered Dose Inhalers

Poonam Sheth, Stephen W. Stein, Paul B. Myrdal

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Pressurized metered dose inhalers (pMDIs) are frequently used for the treatment of asthma and chronic obstructive pulmonary disease. The aerodynamic particle size distribution (APSD) of the residual particles delivered from a pMDI plays a key role in determining the amount and region of drug deposition in the lung and thereby the efficacy of the inhaler. In this study, a simulation model that predicts the APSD of residual particles from suspension pMDIs was utilized to identify the primary determinants for APSD. These findings were then applied to better understand the effect of changing drug concentration and micronized drug size on experimentally observed APSDs determined through Andersen Cascade Impactor testing. The experimental formulations evaluated had micronized drug mass median aerodynamic diameters (MMAD) between 1.2 and 2.6 μm and drug concentrations ranging from 0.01 to 1% (w/w) with 8.5% (w/w) ethanol in 1,1,1,2-tetrafluoroethane (HFA-134a). It was determined that the drug concentration, micronized drug size, and initially atomized droplet distribution have a significant impact in modulating the proportion of atomized droplets that contain multiple suspended drug particles, which in turn increases the residual APSD. These factors were found to be predictive of the residual particle MMAD for experimental suspension HFA-134a formulations containing ethanol. The empirical algebraic model allows predicting the residual particle size for a variety of suspension formulations with an average error of 0.096 μm (standard deviation of 0.1 μm).

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalAAPS PharmSciTech
Issue number1
StatePublished - 2014


  • aerodynamic particle size distribution (APSD)
  • formulation
  • pressurized metered dose inhaler (pMDI)
  • suspension

ASJC Scopus subject areas

  • Pharmaceutical Science


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