Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez BreezhalerA® 150 and 300 μg

Onbrez BreezhalerA (R) is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 mu g dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol BreezhalerA (R) using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 mu g contain equal amounts of lactose per carrier. However, 150 mu g has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 mu g showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 mu g and 300 mu g), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD <= 5 mu m irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter < 3 mu m is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 mu g. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez BreezhalerA (R), and confirm the good practice to make two separate inhalations from the same dose.