Toward Next-Generation Propellants: Assessing Lung Deposition of Beclometasone Dipropionate, Formoterol, and Glycopyrrolate Formulated with HFA-152a Using Functional Respiratory Imaging

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) rely on hydrofluoroalkane (HFA) propellants that have a high global warming potential (GWP). Reformulation with next-generation, low-GWP propellants, such as HFA-152a, offers a strategy to reduce climate impact; however, changes in propellant composition can affect aerosol characteristics and potentially alter lung deposition, requiring robust demonstration of therapeutic equivalence. METHODS: Functional respiratory imaging, combining high-resolution computed tomography and computational fluid dynamics, was used to compare the lung deposition of a fixed triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) delivered via a pMDI formulated with either HFA-134a (Reference) or HFA-152a (Test). Ten patients with chronic obstructive pulmonary disease (GOLD stages 2-4) were retrospectively selected. Patient-specific airway geometries, a standardized inhalation profile, and formulation-specific particle size distributions and plume characteristics were applied. Deposition was quantified in the intrathoracic, central + distal, and peripheral lung regions, and the (central + distal)/peripheral ([C + D]/P) deposition ratio was evaluated. RESULTS: Mean intrathoracic deposition was comparable between the Reference and Test formulations, ranging from 45.95% to 46.88% of the delivered dose (DD). Deposition in the central + distal airways accounted for 12% of DD for both formulations, whereas peripheral deposition predominated, with 33.7% of DD for the Test formulation and 34.5% of DD for the Reference formulation. The (C + D)/P ratios were similar across all active components (0.35-0.37), indicating consistent preferential deposition in the peripheral/small airways. Although inter-patient variability was observed, intra-subject comparisons showed close agreement between propellants. CONCLUSION: Reformulation of the BDP/FF/GB pMDI with the low-GWP propellant HFA-152a preserved total and regional lung deposition characteristics relative to the current HFA-134a formulation. These findings support the maintenance of deposition performance while enabling a substantial reduction in environmental impact, reinforcing the potential of HFA-152a as a next-generation propellant for carbon minimal pMDI therapies.