Transient flow effects in DPI: A computational study linking inhalation dynamics to performance

An ideal Dry Powder Inhaler (DPI) would deliver 100% of the active pharmaceutical ingredient (API) in a fully aerosolized form, regardless of the lung capacity of the patient. In this work, the influence of the instantaneous inhalation flowrate profile on a swirl-based DPI performance is investigated using high-fidelity CFD-DEM simulations of the carrier-API deaggregation, carried out with a customized open-source code specifically optimized for aerosol–particle interaction studies. The study compares four inhalation profiles: an idealized step profile, a realistic inhalation profile for an asthmatic patient, and two ramp profiles that reach the same peak flowrate (PIFR) of 60 L/min as the step profile but with different flow increase rates (FIR): 8.0 L/s 2 for Ramp-1 and 3.9 L/s 2 for Ramp-2. Both powder emission and API deaggregation are analysed to assess the impact of the initial transient phase, showing that deaggregation of the carrier and emission of the API is delayed by over 50 ms in the ramp profiles, and that the fine particle fraction (FPF) decreases by almost 11% for the less steep ramp. These results highlight that, despite identical PIFR, FIR critically influences DPI efficiency, affecting both API deaggregation and carrier recovery. • Flow Increase Rate (FIR) strongly influences deagglomeration and aerosolization in DPI • Transient inhalation profiles with identical PIFR yield different aerosol performance • CFD-DEM simulations indicate that delayed swirl onset may promote particle–particle interactions near the swirl chamber base, potentially leading to re-agglomeration. • Early flow acceleration governs API release, residence time, and carrier recovery • FIR-responsive actuation may improve DPI effectiveness in patients with low inspiratory effort