Delay Between Shaking and Actuation of a Hydrofluoroalkane Fluticasone Pressurized Metered-Dose Inhaler

Respir Care. 2018 Mar;63(3):289-293. doi: 10.4187/respcare.05782. Epub 2017 Nov 21.


Background: Inhaled corticosteroids are used to treat pediatric asthma. The shaking of a pressurized metered-dose inhaler (pMDI) is required to ensure consistency of emitted dose. Delays between shaking and actuating the pMDI are frequent during administration of aerosols to children where a valved holding chamber is used.

Methods: In a recent clinical trial, we used a monitoring device to record shaking and actuation of the pMDI and the inhalation profiles of children with asthma while they were inhaling fluticasone hydrofluoroalkane from a valved holding chamber onto an external filter. During the procedure, in vitro and transport samples were generated without a delay between shaking and actuating the pMDI. Emitted dose, expressed as percentage of ex-actuator nominal dose, obtained from the second actuation following a recorded shake-actuation interval for subjects and from in vitro/transport samples (no delay) were compared.

Results: The mean emitted dose was 158.6% (95% CI 150.1-167.2%) (subjects) and 106.8% (95% CI 104.7-108.9%) (in vitro + transport) of the ex-actuator nominal dose (P < .001). The mean delay between shaking and actuating the pMDI was 12.9 s (95% CI 11.9-13.9 s) for the subject samples. A strong correlation was observed between shake and actuation delay and the emitted dose of the second actuation following the delay (Spearman correlation coefficient = 0.61). A 10-, 20-, and 30-s delay resulted in an emitted dose of the second actuation following the delay of 147, 187, and 227% of the ex-actuator nominal dose, respectively.

Conclusions: Delays between shaking and actuating a corticosteroid suspension pMDI resulted in an increase in the emitted dose of the second actuation following the delay. This can be a common occurrence when doses are administered by a caregiver to a patient via a holding chamber. This should be addressed by practitioners educating patients and parents on proper inhaler use. ( registration NCT01714063.).

Keywords: actuation; delay; drug output; fluticasone; metered-dose inhaler; shaking; suspension; valved holding chamber.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Asthma / drug therapy
  • Bronchodilator Agents / administration & dosage*
  • Child
  • Child, Preschool
  • Female
  • Fluticasone / administration & dosage*
  • Humans
  • Hydrocarbons, Fluorinated
  • Male
  • Metered Dose Inhalers*
  • Pressure
  • Random Allocation
  • Time Factors


  • Aerosols
  • Bronchodilator Agents
  • Hydrocarbons, Fluorinated
  • Fluticasone
  • apaflurane

Associated data