D3.145 - Comparative particle size and distribution from fixed dose triple dry powder inhalers

Small airway disease (SAD) is a clinically relevant and common feature in asthma and COPD. Hence reaching distal airways with extra fine particles ≤2um is important with regard to SAD, especially for the ICS component of triple inhalers to treat eosinophilic inflammation in type 2 high asthma and COPD.  Here we compare in vitro aerodynamic distribution of two fixed dry powder triple inhalers.

Aerodynamic Particle Size Distribution was assessed at 60 L/min for BDP/FF/G DPI (Nexthaler) and 75 L/min for FLU/VI/UMEC DPI (Ellipta) by using a full resolution seven-stage Next Generation Impactor (NGI) plus micro-orifice collector and filter particle collector and a pre-separator between the induction port and Stage 1. Particle size as mass median aerodynamic diameter (MMAD um) and extrafine particle fraction for particles ≤2um (eFPF) as % of delivered dose were compared across inhaler moieties. 

BDP/FF/G exhibited a more homogenous distribution of extra fine particles vs FLU/VI/UMEC. While LABA/LAMA components of both inhalers exhibited broadly comparable eFPF, the ICS component of BDP/FF/G (26.2%; 2.1%) was 3.9-fold higher than FLU/VI/UMEC (6.7%; 0.9%) (Fig. 1). Moreover, particle size as MMAD was much smaller for BDP 1.74um (SD 0.13) vs FLU  4.13um (SD 0.19). 

BDP/FF/G DPI delivers a higher fraction of extra fine ICS particles than FLU/VI/UMEC, in turn reinforcing its potential to optimizing the needed total ICS daily dose and to treat the eosinophilic component of SAD in asthma or COPD. Further clinical studies might clarify the putative clinical impact of these results.