Lois Slator1,2, Owen Currie1, Markus Hijlkema1 & Darragh Murnane2
1Respironics Respiratory Drug Delivery (UK) Ltd, a business of Philips Electronics UK Limited, Chichester, West Sussex, UK
2School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
Summary
The pursuit of more clinically relevant in vitro tests for nebulizers and other inhalation devices continues, as the desire to demonstrate bioequivalence using in vitro data and to refine the predictions of in vivo behaviour is still an ambition. Use of laser diffraction to determine particle size with simulated breathing showed only a minimal decrease in fine particle fraction. Simultaneous measurement of particle size by laser diffractometry and delivered dose by HPLC whilst using the Nephele mixing inlet to introduce a standard adult breathing pattern was assessed and compared to the same parameters recorded under continuous flow extraction. A small decrease in fine particle fraction was observed when a breathing profile was introduced, in line with the previous observations. A much larger percentage decrease in the delivered dose was recorded, even with the sampling time corrected for time spent inhaling. This results in a fine particle dose in the range reported by Svensson et al. in 2018. This outcome suggests that the observed decrease is mainly due to a reduction in drug being delivered to the test system and only slightly due to a change in the aerosol particle size distribution.
Key Message
The reduction in fine particle dose observed when using the Nephele mixing inlet compared to the pharmacopeial method is primarily due to a reduction in drug delivered, whilst the fine particle fraction of that drug is only slightly reduced.