2004 OPEN FORUM Abstracts
VARIABILITY OF THE PARTICLE SIZE DISTRIBUTIONS FROM NEBULIZERS POWERED WITH OXYGEN OR HELIOX.
Gamard, Ph.D., Healthcare R&D, Praxair Inc., Tonawanda, NY;
Timothy E. Corcoran, Ph.D., Division of Pulmonary, Allergy, and
critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
Background: Heliox (mixture of helium and oxygen) is sometimes used to power medical nebulizers. Since the particle size distribution of an aerosol might affect the drug deposition rate in the pulmonary tract, we decided to investigate its dependence on different gas composition and flow rates along with its consistency between nebulizers of the same brand and manufacturer.
Method: Three commercially available nebulizers brands were chosen: Misty-Neb™ (Allegiance Healthcare Corp., McGaw Park, IL), Heart® (Westmed, Tucson, AZ), and Hope Nebulizer™ (B&B Medical Tech. Inc., Loomis, CA) and filled with isotonic saline water. A Malvern Mastersizer S laser diffraction particle size analyzer was used to obtain the particle size distributions. Three devices for each nebulizer brand were used for testing in order to quantify the eventual variation for each product within the same nebulizer brand. Each device arrived sealed and ordered by normal buying channels. Gas was flown at 50 psig in three different concentrations: 100% Oxygen (0/100), 50% Helium/50% Oxygen (50/50), 80% Helium/20% Oxygen (80/20). Flow rate was varied from 5 L/min to 27 L/min depending on the gas composition.
Results: Overall, the Dv (volume median diameter) varied significantly with flow rate, gas composition, and devices within a given nebulizer brand. Increases in flow rate or oxygen concentration tended to decrease the aerosol size. Multiple regression analyses based on minimizing the pooled estimates of the standard deviations were used to try to capture the behavior of the Dv. Different models were tried accounting for linear or higher order dependence on the variables, while still pooling all the data simultaneously. Surprisingly, for each nebulizer brand tested (Misty-Neb™, Heart®, and Hope™), the variation between devices within the same brand was so important that no overall model for the brand could be found (see Table 1).
Conclusion:These particle size tests show that the aerosol properties are highly dependent not only on flow rate and gas composition, but also can significantly vary from one device to the other for the same nebulizer brand. This might eventually affect the overall drug deposition within the respiratory tract. We suggest that investigations including gas-powered medical nebulizers verify the particle size distribution in order to ensure equivalency between tests. This is particularly relevant in studies involving heliox when the gas density affects the aerosol size.
Table 1: Regression model of the experimental testing.
Dv=Do + Ao (Oxygen %)/100 + Aq (flow rate).