Relative particle size and distribution of inhaled triple therapies

  • Brian Lipworth (Lead / Corresponding author)
  • , Enrico Zambelli
  • , Ruben Agazzi
  • , Alessio Piraino

Research output: Contribution to journalArticlepeer-review

Abstract

Background
Many patients with asthma or chronic obstructive pulmonary disease (COPD) 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 COPD to penetrate the small airways.

Objective
We conducted a Next Generation Impactor analysis to compare the aerodynamic particle size distribution of three 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).

Methods
Parameters evaluated included particle size as mass median aerodynamic diameter (MMAD), and extrafine particle fraction (eFPF; diameter < 2µm) 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).

Results
MMAD values for all three 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 three components of BDP/FF/G were also consistent (39.0%–39.9%), and were higher than the other two 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.

Conclusion
BDP/FF/G delivers consistently smaller particles than either BUD/FF/G or FLU/VI/UMEC, translating into a commensurate higher extrafine particle fraction, in turn suggesting greater potential to target the small airways.
Original languageEnglish
JournalAnnals of Allergy, Asthma and Immunology
DOIs
Publication statusAccepted/In press - 19 Dec 2025

Keywords

  • fine particle fraction
  • extrafine particle fraction
  • mass-median aerodynamic diameter
  • inhaled triple therapy
  • inhaled corticosteroid
  • long-acting beta2-agonist
  • long-acting muscarinic antagonist

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