Rapid Screening Particle Size Analysis of Soft Mist Aerosolization Devices

Aurélien Martin¹, Dylan Antoniak², Adam Stuart², Laura Urbano¹ & Darragh Murnane¹

¹University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK

²Merxin Ltd, King’s Lynn Innovation Centre, 1 Innovation Drive, King’s Lynn, PE30 5BY, UK

Summary

Soft mist inhalers (SMI) generate a metered dose of a liquid formulation with an extra-fine droplet size distribution. There is significant interest in the development of new SMI products, and this requires the availability of high throughput performance-screening tools that meet the requirements of regulatory guidelines. The aim of this work was to develop a laser diffraction method which is suitable to assess the size distribution of the rapidly evaporating soft mist aerosols. The aerosol size distribution of a commercially available tiotropium inhalation solution SMI device (UK product licence number PL 14598/0084) was measured for the entire spray duration using a Malvern Panalytical Spraytec instrument and inhalation cell, operating at 30 and 90 L/min as well as at ambient (40-60% RH) and high (98%) relative humidity (RH). When tested at 30 L/min over detectable time frame (when laser beam obscuration is above 2%), the spray duration was observed to increase from 1.5 ± 0.1 seconds at ambient RH to 3.2 ± 0.30 seconds at 98%. Measurements at 90 L/min could not detect any droplets when testing at ambient RH (40-60% RH), preventing a size measurement. However, at 98% RH, the spray duration at 90 L/min was 2.1 ± 0.1 s. A beam steering correction was employed to account for the impact of humidity on the laser scattering signal detection caused by droplet evaporation and inlet air humidity. Aerosol size measurement was restricted to periods where laser beam obscuration was greater than 2%. With the developed method, a volume median diameter of 4.5 ± 0.1 µm was observed, which agrees with literature values.

Key Message

Laser diffraction analysis is suitable to characterise the aerosol size distribution of soft mist aerosols. However, evaporation of the aerosol requires the use of humidity controlled as well as correction for evaporative beam steering air for accurate determination of the droplet size distribution.