Development of an Inline Dry Powder Inhaler That Requires Low Air Volume

摘要

>Background: Inline dry powder inhalers (DPIs) are actuated by an external air source and have distinct advantages for delivering aerosols to infants and children, and to individuals with compromised lung function or who require ventilator support. However, current inline DPIs either perform poorly, are difficult to operate, and/or require large volumes (∼1 L) of air. The objective of this study was to develop and characterize a new inline DPI for aerosolizing spray-dried formulations with powder masses of 10 mg and higher using a dispersion air volume of 10 mL per actuation that is easy to load (capsule-based) and operate.>Methods: Primary features of the new low air volume (LV) DPIs are fixed hollow capillaries that both pierce the capsule and provide a continuous flow path for air and aerosol passing through the device. Two different configurations were evaluated, which were a straight-through (ST) device, with the inlet and outlet capillaries on opposite ends of the capsule, and a single-sided (SS) device, with both the inlet and outlet capillaries on the same side of the capsule. The devices were operated with five actuations of a 10 mL air syringe using an albuterol sulfate (AS) excipient-enhanced growth (EEG) formulation. Device emptying and aerosol characteristics were evaluated for multiple device outlet configurations.>Results: Each device had specific advantages. The best case ST device produced the smallest aerosol [mean mass median aerodynamic diameter (MMAD) = 1.57 μm; fine particle fraction <5 μm (FPF<5μm) = 95.2%)] but the mean emitted dose (ED) was 61.9%. The best case SS device improved ED (84.8%), but produced a larger aerosol (MMAD = 2.13 μm; FPF<5μm = 89.3%) that was marginally higher than the initial deaggregation target.>Conclusions: The new LV-DPIs produced an acceptable high-quality aerosol with only 10 mL of dispersion air per actuation and were easy to load and operate. This performance should enable application in high and low flow mechanical ventilation systems and high efficiency lung delivery to both infants and children.