Impact of aerosol particle size on drug deposition during mechanical ventilation: an in vitro evaluation

Aerosol particle size is thought to impact drug deposition in the lung during controlled mechanical ventilation (CMV). The Aeroneb™ Professional Nebulizer System (Aeroneb Pro, in development), designed for continuous aerosolization with mechanical ventilators, utilizes a micro-pump with domed aperture plate that can be modified to generate fine particle, low-velocity aerosols of specific particle sizes. Thus, the effect of a range of aerosol particle sizes on drug deposition can be studied without changing other nebulizer characteristics.

Methods

To better understand the effect of particle size on drug deposition, six Aeroneb Pro nebulizers were modified to generate aerosols ranging from 3.4 to 5.4 μm volume median diameter (VMD), as determined by laser diffraction (Spraytech™; Malvern). Albuterol sulfate (0.5 ml of 0.5% solution) was aerosolized using an Aeroneb Pro placed in the humidified inspiratory limb of a Puritan Bennett 760 Ventilator (tidal volume of 500 ml, peak flow 40 l/min, ramp flow pattern, I:E ratio 1:3, rate 15/min) attached to an intubated adult lung model. The amount of drug deposited on an absolute filter distal to an 8 mm ID endotracheal tube was determined for each aerosol particle size (n = 3). Drug was eluted from the filter and determined by reverse phase HPLC with isocratic elution and UV detection at 275 nm.

Results

The percent of the total dose administered ± standard deviation (SD) which was deposited in the test lung for each VMD tested is shown in the Table.

Table

Summary

There was an inverse correlation (P < 0.05, least squares analysis) between deposition of drug and aerosol particle size across the range of particle sizes tested. The efficient deposition (19–40%) of the 0.5 ml dose of albuterol is due, in part, to the low residual volume of the Aeroneb Pro.

Conclusion

Smaller aerosol particles resulted in greater drug delivery in vitro when using the modified Aeroneb Pro during CMV. Further studies are warranted to better understand this relationship, and to confirm this relationship in vivo.