Developing an in vitro understanding of patient experience with hydrofluoroalkane-metered dose inhalers

J Pharm Sci. 2014 Nov;103(11):3648-3656. doi: 10.1002/jps.24167. Epub 2014 Sep 16.


As a result of the Montreal Protocol on Substances that Deplete the Ozone Layer, manufacturers of metered dose inhalers began reformulating their products to use hydrofluoroalkanes (HFAs) as propellants in place of chlorofluorocarbons (CFCs). Although the new products are considered safe and efficacious by the US Food and Drug Administration (FDA), a large number of complaints have been registered via the FDA's Adverse Events Reporting System (FAERS)-more than 7000 as of May 2013. To develop a better understanding of the measurable parameters that may, in part, determine in vitro performance and thus patient compliance, we compared several CFC- and HFA-based products with respect to their aerodynamic performance in response to changes in actuator cleaning interval and interactuation delay interval. Comparison metrics examined in this study were: total drug delivered ex-actuator, fine particle dose (<5 μm), mass median aerodynamic diameter, plume width, plume temperature, plume impaction force, and actuator orifice diameter. Overall, no single metric or test condition distinguishes HFA products from CFC products, but, for individual products tested, there were a combination of metrics that differentiated one from another.

Keywords: HPLC (high performance/pressure liquid chromatography); aerosols; analysis; metered dose inhalers; pulmonary; pulmonary drug delivery.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Aerosol Propellants / administration & dosage
  • Aerosol Propellants / adverse effects
  • Aerosol Propellants / chemistry*
  • Aerosols
  • Chemistry, Pharmaceutical
  • Chlorofluorocarbons / administration & dosage
  • Chlorofluorocarbons / adverse effects
  • Chlorofluorocarbons / chemistry*
  • Equipment Design
  • Humans
  • Hydrocarbons, Fluorinated / administration & dosage
  • Hydrocarbons, Fluorinated / adverse effects
  • Hydrocarbons, Fluorinated / chemistry*
  • Medication Adherence*
  • Metered Dose Inhalers*
  • Particle Size
  • Patient Satisfaction*
  • Respiratory System Agents / administration & dosage
  • Respiratory System Agents / adverse effects
  • Respiratory System Agents / chemistry*
  • Risk Assessment
  • Solvents / chemistry
  • Temperature


  • Aerosol Propellants
  • Aerosols
  • Chlorofluorocarbons
  • Hydrocarbons, Fluorinated
  • Respiratory System Agents
  • Solvents
  • apaflurane