Abstract / Summary
Background: The therapeutic efficacy of inhaled triple-combination therapy in chronic obstructive pulmonary disease (COPD) depends on efficient delivery to peripheral airways.This study evaluated the influence of particle morphometrics on pulmonary deposition and bronchodilator response to glycopyrronium-formoterol-budesonide (GFB) inhalation formulations.Methods: Three commercial GFB formulations (X, Y, and Z) delivered via metered-dose inhaler (MDI) and dry powder inhaler (DPI) were characterized using dynamic light scattering and scanning electron microscopy.In a randomized, open-label pilot study, twenty-four patients with mild-to-moderate COPD inhaled technetium-99m (99mTc) radiolabeled formulations.Regional lung deposition was assessed by planar gamma scintigraphy, and central-to-peripheral (C/P) ratios were calculated.Forced expiratory volume in one second (FEV1) was measured at baseline and 30 minutes post-inhalation.Results: Significant inter-brand differences in particle morphometrics were observed.Brand X demonstrated a narrow particle distribution (1.3±0.26µm) with uniform spherical morphology, while brands Y and Z showed relatively broader, polydisperse distributions with irregular particles.MDIs (MIX, MIY, MIZ) consistently outperformed DPIs (DIX, DIY, DIZ), producing greater total lung deposition (23.4% vs 13.7%; P < 0.001) and improved peripheral deposition.Among MDIs, MIX achieved higher intrathoracic deposition (28.8 ± 2.2% vs 19.0-22.5%;P < 0.001) and peripheral deposition (15.8 ± 3.0% vs 9.8-11.5%;P = 0.012), with a lower C/P ratio (0.82 vs 0.96-1.0).Greater spirometric improvement correlated with enhanced deposition, with the MIX producing the highest FEV1 increase (12.8%;P < 0.05).Conclusions: The findings suggest that particle size distribution, polydispersity, and surface morphology may influence pulmonary deposition and acute spirometric response in COPD.A relatively narrow respirable particle distribution may support more consistent peripheral airway deposition and short-term spirometric response.