Production of inhalable submicrometer aerosols from conventional mesh nebulizers for improved respiratory drug delivery

Abstract

Submicrometer and nanoparticle aerosols may significantly improve the delivery efficiency, dissolution characteristics, and bioavailability of inhaled pharmaceuticals. The objective of this study was to explore the formation of submicrometer and nanometer aerosols from mesh nebulizers suitable for respiratory drug delivery using experiments and computational fluid dynamics (CFD) modeling. Mesh nebulizers were coupled with add-on devices to promote aerosol drying and the formation of submicrometer particles, as well as to control the inhaled aerosol temperature and relative humidity. Cascade impaction experiments were used to determine the initial mass median aerodynamic diameters of 0.1% albuterol aerosols produced by the AeroNeb commercial (4.69 μm) and lab (3.90 μm) nebulizers and to validate the CFD model in terms of droplet evaporation. Through an appropriate selection of flow rates, nebulizers, and model drug concentrations, submicrometer and nanometer aerosols could be formed with the three devices considered. Based on CFD simulations, a wire heated design was shown to overheat the airstream producing unsafe conditions for inhalation if the aerosol was not uniformly distributed in the tube cross-section or if the nebulizer stopped producing droplets. In comparison, a counter-flow heated design provided sufficient thermal energy to produce submicrometer particles, but also automatically limited the maximum aerosol outlet temperature based on the physics of heat transfer. With the counter-flow design, submicrometer aerosols were produced at flow rates of 5, 15, and 30 LPM, which may be suitable for various forms of oral and nasal aerosol delivery. Thermodynamic conditions of the aerosol stream exiting the counter-flow design were found be in a range of 21-45 °C with relative humidity greater than 40% in some cases, which was considered safe for direct inhalation and advantageous for condensational growth delivery.

Improving Aerosol Drug Delivery During Invasive Mechanical Ventilation With Redesigned Components

“…While not currently in clinical use for ventilation circuits, the two mesh nebulizers selected produce aerosols with sizes (MMAD ϭ 4.84 -5.30 m) very similar to typically used vibrating mesh devices 3,4,25 like the AeroNeb Pro (Aerogen Limited), with a MMAD of 4.7 m. 26 The Aeroneb Lab device was expected to produce aerosol sizes smaller than the commercial Pro version to maximize lung delivery, 26 but a difference in aerosol size was not observed in this study. Similarly, the output rate of drug mass was similar to clinical devices with ϳ380 g of drug emitted from the Aeroneb Lab nebulizer in 30 s. Typical doses of AS for ventilated patients are 400 g from metered-dose inhalers 2 and on the order of 1 mg from nebulizers, 4 with nebulizer delivery periods of up to 15 min.…”

High-Efficiency Generation and Delivery of Aerosols Through Nasal Cannula During Noninvasive Ventilation

“…Performance of the Aeroneb Lab device was previously reported by Longest et al (23) and includes a liquid aerosolization rate of 0.2 mL/min, an initial aerosol MMAD of 3.9 lm, and a particle number concentration of 4.28 · 10 5 part/cm 3 in an airflow of 15 L/min based on a monodisperse aerosol approximation. The mesh nebulizer output is combined with ventilation gas using a mixing apparatus.…”

“…The previous study of Longest et al (23) considered a radial mixer design where inlet ventilation gas was combined with the aerosol using a porous shell characterized by 2-mm holes (Fig. 1a).…”

“…To facilitate the use of submicrometer and nanometer aerosols combined with controlled condensational growth, Longest et al (23) considered the formation of submicrometer particles from conventional mesh nebulizers. A radial mixer design was used to combine a gas delivery stream with aerosols produced from the Aeroneb Pro and Aeroneb Lab nebulizers (Aerogen).…”

“…As described by Longest et al, (23) the thermal energy needed to evaporate the aerosol requires relatively high flow rates at temperatures that are safe for inhalation. In the improved design, heated air enters the counterflow heat exchanger at a total flow rate of 80 L/min (40 L/min per channel).…”