Towards a More Realistic Method for Measuring Nebulized Aerosols: Combining a Nephele Mixing Inlet with Laser Diffraction

Lois Slator


The development of a clinically relevant test methodology for respirable dose that more closely mimics the in vivo situation of aerosol delivery under tidal breathing conditions should allow better in vitro-in vivo correlation and hence increase the relevance of in vitro testing. This work builds upon the method developed by Svensson et al (AAPS PharmSciTech. 2018;19(2):565-572) by replacing the cascade impactor with a laser diffraction analyser, allowing for observations of the aerosol particle size distribution (APSD) at each point of the breath cycle  rather than capturing the final distribution provided by the cascade impactor. Nebulisers may vary output with the breathing cycle due to their design and so VMD and Fine Particle fraction may also. A test setup has been developed and assessed, using a Nephele Mixing Inlet to provide a constant flow rate through the laser diffraction inhalation cell during simulation of an adult breathing pattern. The increased aerosol pathway created by adding the Mixing Inlet was found to have little effect on the volume median diameter (VMD). The testing of a trapezoidal waveform showed that the requirements of the laser diffraction method could still be met and that the production of an aerosol bolus during the changes in flow rate direction from inhalation to exhalation did not prevent measurement of the APSD. The repeatability of the method was demonstrated by the low standard deviations recorded for each test point. The obscuration profiles during the adult breath pattern suggested that the flows within the test set up were not laminar and may require further investigation.

Key Message

The results of these preliminary investigations suggest that use of the Nephele mixing inlet method is promising for provision of a more clinically relevant method for the assessment of APSD during simulated breathing when testing the output of mesh nebulizers with a SprayTec laser particle sizer, but further research to investigate the unexpected obscuration profiles recorded may be required.

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