In vitro comparison of the effect of inhalation delay and flow rate on the emitted dose from three valved holding chambers

J Aerosol Med Pulm Drug Deliv. 2014 Aug;27 Suppl 1:S37-43. doi: 10.1089/jamp.2013.1061. Epub 2014 Jan 29.


Background: Valved holding chambers (VHCs) are accessory devices for pressurized metered dose inhalers (pMDIs). Use of a VHC may help overcome coordination issues associated with drug delivery via the pMDI alone. Previous work has established that aspects of VHC use, including the time between actuation and inhalation (inhalation delay) and inhalation flow rate, can influence the amount of drug available to inhalation. This study compared the impact of inhalation delay and flow rate on the in vitro delivery of aerosol from different VHC brands.

Methods: A custom-built inhalation delay test rig, which enabled automation of controlled inhalation delays (0, 5, or 10 sec), was developed. Extraction air flow was set to 5, 15, or 30 L/min. Delivery of albuterol (ProAir HFA 90 μg) to a filter (emitted dose) was assessed using three commercially available VHC brands (one conventional, two antistatic). Emitted dose under 27 different combinations of inhalation delay, flow rate, and VHC brand was determined in order to assess the effects of inhalation delay and flow rate. Pairwise comparisons of the different VHC brands with different inhalation delay/flow rate combinations were conducted to assess in vitro equivalence.

Results: Emitted dose increased with flow rate and decreased with longer inhalation delays. Dependence on flow rate was similar for the two antistatic VHCs and more pronounced for the conventional VHC. The two antistatic VHCs showed equivalent results for the emitted dose of albuterol, across a range of flow rates and using different inhalation delays; the relation between the two antistatic VHCs fell within the ± 15% acceptance interval criteria for in vitro equivalence.

Conclusions: The different inhalation delays and flow rates had similar effects on the delivery of drug via the three VHCs. The two antistatic VHCs were shown to be equivalent in vitro in terms of emitted dose of albuterol.

Keywords: emitted dose; flow rate; in vitro equivalence; inhalation delay; pMDI; valved holding chamber.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Albuterol / administration & dosage*
  • Albuterol / chemistry
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems / instrumentation*
  • Equipment Design
  • Humans
  • Inhalation*
  • Metered Dose Inhalers*
  • Particle Size
  • Pressure
  • Rheology
  • Time Factors


  • Aerosols
  • Albuterol