Comparative In Vitro Deposition Analysis of Formoterol, Glycopyrronium, and Tiotropium Delivered via Capsule-Based DPI

Dry powder inhalers (DPIs) are the mainstay in the treatment of obstructive pulmonary diseases. However, the performance of DPI formulations is highly dependent on the used inhaler device and the patient's inspiratory effort. This study aimed to evaluate and compare the aerosolization behavior of three commercially available capsule-based DPI medications-formoterol (Foradil^®), glycopyrronium (Seebri^® Breezhaler), and tiotropium (Spiriva^®)-delivered using three different capsule-based inhalers (Aerolizer, Breezhaler, and Handihaler), under varying flow conditions. <b>Methods:</b> The aerodynamic performance of each formulation-inhaler combination was assessed using the Next-Generation Impactor (NGI) and Dosage Unit Sampling Apparatus (DUSA) methodology. Fine particle dose (FPD) and aerodynamic particle size distribution (APSD) were determined at fixed flow rates of 15, 30, 60, and 100 L/min, as well as at inhaler-specific flow rates corresponding to a 4 kPa pressure drop. Chromatographic quantification of active ingredients was performed using validated HPLC methods specific to each drug. <b>Results:</b> The FPD values increased consistently with higher flow rates across all tested formulations and inhalers. At a 4 kPa pressure drop, Aerolizer and Breezhaler achieved significantly higher FPDs compared to Handihaler. Notably, in some instances, non-dedicated inhalers produced greater respirable fractions than the originally intended devices. APSD profiles revealed that drug deposition shifted toward smaller NGI stages at higher inspiratory flows, supporting enhanced deep lung delivery potential under optimal conditions. <b>Conclusions:</b> Device resistance, capsule orientation, and piercing mechanics substantially influence drug aerosolization. Although non-dedicated inhalers may offer improved FPDs in vitro, clinical use should adhere to approved drug-device combinations, as these have been validated for efficacy and safety under real-world conditions.