title: Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone.
abstract: Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.
authors.affiliation: 3M Pharmaceuticals, ST Paul, MN 55144-1000, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Leach
authors.forename: P J
authors.initials: PJ
authors.lastname: Davidson
authors.forename: R J
authors.initials: RJ
authors.lastname: Boudreau
mesh_terms: D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001623:Betamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017402:Chlorofluorocarbons; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000378:metabolism; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D001623:Betamethasone; D017402:Chlorofluorocarbons; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons