Application of heated inlet extensions to the TSI 3306/3321 system: Comparison with the Andersen cascade impactor and next generation impactor

Paul B. Myrdal, Erik Mogalian, Jolyon Mitchell, Mark Nagel, Charlie Wright, Brent Kiser, Mark Prell, Mike Woessner, Stephen W. Stein

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Pharmaceutical aerosol size distribution analysis based on multi-stage inertial impaction is well accepted, though laborious. The TSI 3306 Impactor Inlet/3321 time-of-flight (TOF) Aerodynamic Particle Size Analyzer (APS®) has been evaluated for its ease of use and potential for time savings during product development. However, instrument inlet modifications may be necessary for increased correlation with equivalent measurements obtained by inertial impaction following pharmacopeial methods. A heated inlet extension tube was located between the USP/Ph.Eur. throat and the Single-Stage Impactor (SSI) to promote evaporation of residual ethanol from aerosol droplets, generated from two formulations containing ethanol as semi-volatile solubilizer (8 and 20% w/w) for the active pharmaceutical ingredient. As temperature and extension length increased, the SSI-measured fine particle fraction (aerosol < 4.7 μm aerodynamic diameter) also increased, for the aerosols used in this study. These values correlated quite closely with equivalent measures made by multi-stage cascade impactor equipped with the same throat. Particle size distribution profiles measured with the APS for either formulation did not significantly change utilizing the heated extensions, suggesting that ethanol evaporation was largely complete at any condition by the time the aerosol entered the measurement zone of the TOF analyzer. The addition of a heated inlet extension may be useful to facilitate evaporation of residual semi-volatile species, especially when an agreement of APS-derived particle size mass distribution data from the SSI with multi-stage cascade impactors is desired. However, complete evaporation of the semi-volatile species may not be necessary for SSI-generated mass distribution to match conventionally used cascade impactors.

Original languageEnglish (US)
Pages (from-to)543-554
Number of pages12
JournalJournal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung
Issue number4
StatePublished - 2006


  • Andersen cascade impactor
  • Impactor inlet
  • MDI
  • Metered dose inhaler
  • Next generation impactor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)


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