Relative particle size and distribution of inhaled triple therapies

Many patients with asthma or chronic obstructive pulmonary disease have small airways dysfunction, the presence of which has clinical implications including poor disease control and worse health status. It is, therefore, important to evaluate the ability of an inhaled product used for the treatment of asthma or chronic obstructive pulmonary disease to penetrate the small airways.

To compare the aerodynamic particle size distribution of 3 triple combination inhalers: beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G), budesonide/formoterol fumarate/glycopyrronium (BUD/FF/G), and fluticasone furoate/vilanterol/umeclidinium (FLU/VI/UMEC).

Parameters evaluated via a Next Generation Impactor analysis included particle size as mass median aerodynamic diameter and extrafine particle fraction (eFPF; diameter < 2 µm) calculated as a percentage of the delivered dose. The mass of each component was evaluated using high-performance liquid chromatography assays (FF as the dihydrate salt, G as the bromide salt, VI as the trifenatate salt, and UMEC as the bromide salt).

Mass median aerodynamic diameter values for all 3 components of BDP/FF/G were consistent (1.1 µm) and were lower than BUD/FF/G (3.02-3.36 µm) and FLU/VI/UMEC (1.96-4.13 µm). Mean eFPFs of the 3 components of BDP/FF/G were also consistent (39.0%-39.9%) and were higher than those of the other 2 therapies (BUD/FF/G, 10.5%-16.2%; FLU/VI/UMEC, 6.8%-27.7%), especially for the BDP component, which was 3.8-fold higher than BUD and 5.8-fold higher than FLU.

BDP/FF/G delivers consistently smaller particles than either BUD/FF/G or FLU/VI/UMEC, translating into a commensurate higher eFPF, in turn suggesting greater potential to target the small airways.