In Vitro Evaluation of Aerosol Performance and Delivery Efficiency During Mechanical Ventilation Between Soft Mist Inhaler and Pressurized Metered-Dose Inhaler

Soft mist inhalers (SMIs) generate aerosols with a smaller particle size than pressurized metered-dose inhalers (pMDIs). However, the whole-span particle size distribution (PSD) of SMIs and the optimal delivery method of SMIs during mechanical ventilation have not been fully investigated. This study aimed to measure the PSD of the SMI alone and the SMI coupled to an inhalation aid (eg, a spacer, a valved holding chamber), as well as the delivery efficiency of SMI in different actuation timings and circuit positions during mechanical ventilation. As a suitable comparison, the pMDI was chosen for the same measurement. SMIs (2.5 μg/actuation of tiotropium) were compared with pMDIs (100 μg/actuation of salbutamol). A microorifice uniform deposit impactor was utilized for the particle sizing of drug aerosols generated by inhalers alone, inhalers with a spacer, and inhalers with a valved holding chamber. To optimize the delivery efficiency of both inhalers during mechanical ventilation, the operating parameters included the circuit positions and actuation timings in the ventilator circuit. Particle sizes and inhaled doses were measured with an optical particle sizer and filters used to collect and quantify the drug, respectively. The SMI generated a smaller mass medium aerodynamic diameter (MMAD) than that from the pMDI. The extrafine-particle fraction (EFPF, < 1 μm) of the SMI was significantly higher than that of the pMDI. With the use of either inhalation aid, the MMAD of both inhalers decreased, and both inhalers with inhalation aid showed significant increases in EFPF. During mechanical ventilation, the optimum way to deliver the SMI and pMDI was at 15 cm from the Y-piece and actuated at the end of expiration and the onset of inspiration, respectively. The SMI with an inhalation aid showed marginal improvement on the PSD. The inhaler type, actuation timing, and position within the circuit also played important roles in delivery efficiency during mechanical ventilation.