The Influence of Breathing Pattern During Nebulization on the Delivery of Arformoterol Using a Breath Simulator

Patients with obstructive airway conditions, including chronic obstructive pulmonary disease (COPD), use nebulizers for drug delivery. Tidal breathing patterns employed by patients during nebulized drug delivery may vary. It is unclear whether different breathing patterns affect the emitted quantity of nebulized drug. This in vitro study evaluated whether different tidal breathing patterns that encompass a range that could be observed in COPD patients influence the emitted amount of nebulized arformoterol. Breath-simulation experiments used a Pari LC Plus nebulizer in combination with the Duraneb 3000 portable aerosol system. Four breathing patterns that could represent a range of tidal volumes and inspiratory and expiratory times observed in patients with COPD were studied. The amount of arformoterol on the inspiratory and expiratory filters, and the residual amount in the nebulizer bowl were determined via high-pressure liquid chromatography. Results are expressed as a percent of the nominal dose (15 microg in 2 mL). The total amount of arformoterol on the inspiratory filter increased with a longer inspiratory phase of tidal breathing (ranging from 8.0% to 13.1%), while the expiratory filter dose remained similar (7.9% to 8.7%). The total emitted dose (expiratory and inspiratory amounts combined) for all patterns was 16.0% to 21.1% of the nominal dose. Retained arformoterol amount (not emitted) ranged from 55.9% to 62.3% of the nominal dose. These breath-simulation experiments suggest that only about 20% of the nominal 15-microg arformoterol dose was emitted from the nebulizer apparatus with each of the 4 tidal breathing patterns studied, and that a longer inspiratory phase was associated with greater inhaled dose.