Pulmonary Delivery of Isoproterenol Aerosol Generated With Silicon-Based MHz Ultrasonic Nozzles

Monodisperse micron-sized aerosol is ideal for pulmonary drug delivery. This paper reports delivery of monodisperse aerosol of medicinal droplets generated by MHz ultrasonic nozzles using an anatomically realistic upper airway model. The MHz ultrasonic nozzle is fabricated using MEMS technology, and comprised of a piezoelectric drive section and a silicon resonator of multiple Fourier horns (see Fig. 1) [1]. The dissolved medication is pumped into a central channel (200×200 μm²) inside the nozzle and exits at the nozzle tip that vibrates longitudinally at the nozzle resonant frequency. The novel design of multiple horns facilitates generation of a column of monodisperse droplets at electric drive power as low as 15mW [1]. Monodisperse ethanol droplets 2.4 μm and water droplets 4.5 μm in diameter have been produced, respectively, using 1.5 MHz and 1.0 MHz nozzles. We used an aqueous solution of 25mg/ml (2.5wt%) β₂-agonist (isoproterenol) for generation of monodisperse droplets using the 1.0 MHz ultrasonic nozzles. A yield of >54% (to the lower airways on total amount of inhaled isoproterenol basis), significantly higher than the reported highest lower airways deposition (32%) using metered-dose-inhalers (MDIs) [2], has been accomplished.