Hydraulic High-Pressure Nebulization of Solutions and Dispersions for Respiratory Drug Delivery*

Abstract

The purpose of this investigation was to assess hydraulic high-pressure nebulization as a means for respiratory drug delivery. A hydraulic high-pressure nebulizer was designed and constructed. In a design study, the output efficiency and the aerosol particle size were determined for the nebulizer as a function of nozzle diameter (5, 10, and 20 μm), gas flow rate (2 and 8 l/min), applied hydraulic pressure (2200 and 4000 psig), and distance between the nozzle orifice and impaction surface (0.25–4 cm) with an aqueous solution of fluorescein. The output efficiency was also measured with an ethanol solution and an aqueous phospholipid dispersion of liposomes. For the design study, each factor had an effect. The efficiency tended to increase with a decrease in the nozzle diameter, although the differences between the 5- and 10-μm nozzle were more sensitive to the air flow rate and nozzle-to-impaction-surface distance. Greater efficiencies were always obtained at the higher ancillary air flow rates. Operating the nebulizer at different pressures caused a change in the functional relationship between the efficiency and the nozzle-to-impaction-surface distance. For the 5-μm nozzle at high pressure, efficiency fell with increasing nozzle-to-impaction-surface distance, whereas for the data obtained with the 20-μm nozzle, the efficiency increased with nozzle-to-impaction-surface distance, with lower efficiencies obtained at the higher pressures. For the remaining observations made with the 5- and 10-μm nozzles, the efficiency as a function of nozzle-to-impaction-surface distance appeared to be variable. For the 5- and 10-μm size nozzle, there was no significant effect of the air flow rate, pressure, or nozzle-to-impaction-surface distance on the mass median aerodynamic diameter and geometric standard deviation. For the 20-μm size nozzle, the particles were not completely dried. Ethanol solutions gave somewhat higher efficiencies, whereas the phospholipid dispersion gave efficiencies comparable to the aqueous solutions nebulized under similar conditions. The efficiency of the hydraulic high-pressure nebulizer appears to be correlated with the calculated properties of the liquid jet. For respiratory drug delivery, the hydraulic high-pressure nebulizer provides reasonably high outputs of respirable particles independent of time from a single pass of liquid through the nebulizer.