Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler.

The objective of this study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP) from a breath-activated inhaler (QVAR Autohaler) compared with proper and improper press and breathe (QVAR P&B) metered dose inhaler (MDI) technique. The hypothesis was that that the smaller particles of BDP from HFA-BDP would stay suspended longer in the inspiratory air of patients and thus reduce the deleterious effects of inhaler discoordination. The study was an open label, four period, cross-over design. Asthmatic patients (n = 7) with a history of asthma symptoms, an FEV-1 of >70% of predicted normal, and a history of reversibility to a beta-agonist of >or=12% were utilized. BDP was radiolabeled with technetium-99m and delivered from the QVAR Autohaler or QVAR P&B device in patients trained to reproducibly utilize coordinated and discoordinated P&B MDI technique. Patients using Autohaler MDI exhibited 60% lung deposition of BDP. Patients using coordinated technique with the P&B MDI exhibited 59% lung deposition. Patients trained to consistently actuate the P&B MDI before inhaling exhibited 37% lung deposition. Patients trained to consistently actuate the P&B MDI late in the inspiration (i.e., 1.5 sec into a 3-sec inspiration) exhibited 50% lung deposition. In conclusion, the breath-activated Autohaler automatically provided optimal BDP lung deposition of 60%. Patients with good P&B MDI technique also received optimal lung deposition of 59%. The degree of lung deposition was decreased as patients demonstrated poor inhaler technique. However patients with poor technique still received a large lung dose of BDP (i.e., >or=37%) compared with lung deposition values of 4-7% for CFC-BDP MDIs previously published and confirmed in this study.

Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone : a cross-over study in healthy volunteers.

STUDY OBJECTIVES: To compare the lung deposition of radiolabeled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) with chlorofluorocarbon fluticasone propionate (CFC-FP) and chlorofluorocarbon beclomethasone (CFC-BDP). DESIGN: Six-day, open-label, nonrandomized, crossover study. SETTING: Clinical research laboratory. PARTICIPANTS: Nine healthy, nonsmoking, adult volunteers. INTERVENTIONS: On each study day, participants inhaled one or two puffs of 99mTc-labeled HFA-BDP, CFC-FP, or CFC-BDP. All products delivered 50 micro g per puff ex-valve. Subjects used a respiratory training and monitoring device to meet predefined, standardized inhalation patterns. Immediately after inhalation of radiolabeled study drug, planar gamma camera images were obtained. MEASUREMENTS AND RESULTS: Radiolabeled HFA-BDP had a higher deposition in the lungs (53% ex-actuator) compared with CFC-FP (12 to 13%) and CFC-BDP (4%). Conversely, CFC-FP and CFC-BDP had a much higher distribution to the oropharynx (72 to 78%, and 82%, respectively) than HFA-BDP (29%). HFA-BDP was deposited evenly throughout the lungs, while CFC-FP and CFC-BDP deposition was primarily in the large central and intermediate airways. Andersen particle size sampling gave mass median aerodynamic diameters for HFA-BDP, CFC-FP, and CFC-BDP of 0.9 micro m, 2.0 micro m, and 3.5 micro m, respectively. CONCLUSIONS: Lung deposition was greater with HFA-BDP compared with CFC-FP and CFC-BDP. Deposition values appeared to be related to the particle size distribution of each inhaler, with the smaller particles of HFA-BDP providing the greatest lung deposition and least oropharyngeal deposition.