title: Plume Characteristics of Two HFA-Driven Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combination Pressurized Metered-Dose Inhalers.
abstract: BACKGROUND
  New inhalers propelled by hydrofluoroalkanes (HFAs) have improved plume characteristics: higher fine particle fraction, and warmer plumes with reduced force and velocity. Together, this may avoid reflex interruption of inhalation and improve lung deposition of the inhaled drugs. However, even with HFA-propelled pressurized metered-dose inhalers (pMDIs), there are notable differences in device properties. Here we compared the duration, velocity, force, and temperature of two inhaled corticosteroid/long-acting β2-agonist combination therapies, administered via HFA pMDIs: fluticasone propionate/formoterol 125/5 µg (FP/FORM; flutiform(®)) and fluticasone propionate/salmeterol 125/25 µg (FP/SAL; Seretide(®) Evohaler(®)).
  
  
  METHODS
  Inhalers were fired into ambient air. Plume duration and velocity were recorded with a high-speed camera and a pulsed laser light source. A copper disc attached to a sensitive load cell measured the plume force at various distances from the device. A thermal imaging video camera recorded impaction temperature in line with the device.
  
  
  RESULTS
  The average plume duration for FP/FORM was longer than that of FP/SAL: 168.3 vs. 114.0 ms, respectively. The mean maximum plume velocities observed at 95 mm (the approximate distance between mouthpiece and throat) was consistently slower for FP/FORM (10.08 m/s) compared to FP/SAL (15.55 m/s). FP/FORM had a slower velocity at the outset, remaining relatively constant before declining steadily over the plume duration. The force of the FP/SAL plume was greater than that of FP/FORM at all distances: maximum force for FP/FORM was 138.2 vs. 278.9 mN for FP/SAL. The minimum impaction temperature was +5.9 °C for FP/FORM and -37.8 °C for FP/SAL; this difference became less pronounced over distance.
  
  
  CONCLUSIONS
  There were substantial differences between the plumes of the two pMDIs. FP/FORM was warmer, less forceful, had a longer plume duration and slower maximal velocity. These plume characteristics of FP/FORM may lead to improved lung deposition.
  
  
  BACKGROUND
  Mundipharma Research Limited, Cambridge, UK.
authors.affiliation: Mundipharma Research Ltd, Unit 191, Cambridge Science Park, Milton Road, Cambridge, CB4 0GW, UK, Baljinder.Johal@mundipharma-rd.eu.
authors.forename: Baljinder
authors.initials: B
authors.lastname: Johal
authors.forename: Séamus
authors.initials: S
authors.lastname: Murphy
authors.forename: John
authors.initials: J
authors.lastname: Tuohy
authors.forename: Jonathan
authors.initials: J
authors.lastname: Marshall
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000335:Aerosol Propellants / Q000737:chemistry*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D004359:Drug Therapy, Combination; D000068298:Fluticasone / Q000008:administration & dosage; D000068759:Formoterol Fumarate / Q000008:administration & dosage; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D036501:Metered Dose Inhalers; D009330:Nebulizers and Vaporizers; D000068299:Salmeterol Xinafoate / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D000335:Aerosol Propellants; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000068759:Formoterol Fumarate