A pilot study to assess lung deposition of HFA-beclomethasone and CFC-beclomethasone from a pressurized metered dose inhaler with and without add-on spacers and using varying breathhold times.
BACKGROUND
The study objective of this pilot study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP; QVAR™) and CFC-beclomethasone dipropionate (CFC-BDP; Becloforte™) with and without the add-on spacers, Aerochamber™, and Volumatic™. The smaller particles of HFA-BDP were presumed to produce greater lung deposition using spacers, with and without a delay [i.e., metered dose inhaler (MDI) actuation into the spacer and subsequent inhalation 0 and 2 sec later], compared with the larger particles of CFC-BDP. The study included a comparison of breathhold effects (i.e., 1 and 10-sec breatholds) on lung deposition.


METHODS
The study was an open-label design and utilized healthy subjects (n = 12 males). Each arm of the study contained three subjects; thus, outcomes were not powered to assess statistical significance. HFA-BDP and CFC-BDP were radiolabeled with technetium-99m and delivered to subjects.


RESULTS
Results showed that the small particle HFA-BDP lung deposition averaged 52% and was not affected by the use of Aerochamber with or without a spacer delay. The oropharyngeal deposition of HFA-BDP was reduced from approximately 28% to 4% with the Aerochamber. Lung deposition with the large particle CFC-BDP was 3-7% and generally decreased with Aerochamber or Volumatic. A 2-sec time delay between actuation and breath plus the spacer reduced lung deposition slightly but reduced oropharygeal deposition substantially (84% down to 3-20%) using the Aerochamber or Volumatic with and without a spacer delay. HFA-BDP lung deposition was dependent on the breathhold. Lung deposition with HFA-BDP was reduced by 16% with a 1-sec versus 10-sec breathhold. The difference was measured in the increased exhaled fraction, confirming that smaller particles need time to deposit and are exhaled if there is a reduced breathhold. The large particle CFC-BDP lung deposition was not affected by breathhold.


CONCLUSIONS
The use of Aerochamber or Volumatic spacers with HFA-BDP did not alter lung deposition but it did reduce oropharyngeal deposition. However, HFA-BDP displayed reduced oropharyngeal deposition without a spacer.
Leach
Chet L
CL
3M Pharmaceuticals, St. Paul, Minnesota, USA. cleach@lrri.org
Colice
Gene L
GL
D000280:Administration, Inhalation; D000328:Adult; D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D001507:Beclomethasone / Q000493:pharmacokinetics*; D017402:Chlorofluorocarbons; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008168:Lung / Q000378:metabolism*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D010316:Particle Size; D010865:Pilot Projects; D012119:Respiration; D013667:Technetium; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; D013667:Technetium; C094049:apaflurane; D005466:Fluorocarbons