Abstract

Summary Background: In bronchial challenge testing lung deposition of the stimulus may be poorly controlled due to incorrect use of nebulisers. Furthermore, the need for freshly prepared solutions burdens personnel and budget. In this study we aim to develop a dry powder alternative with higher reproducibility, better stability and lower costs than the current nebulisation test. Methods: Different pharmacological stimuli in the solid state were characterised on physico-chemical properties to determine the optimal conditions for processing and storage and were tested on their potential for dry powder inhalation. Adenosine and methacholine were micronised and dispersed with the Twincer ™ dry powder inhaler (DPI). Laser diffraction technique was applied to measure particle size distributions in the aerosol clouds. Results: Adenosine allows processing under ambient conditions. It was mixed with a lactose carrier in various mass ratios to produce adhesive mixtures and nucleus agglomerates. With three formulations, almost the entire dose range could be delivered with the Twincer ™ DPI. However, the process of preparing nucleus agglomerates might not be suitable for upscaling. Currently, spherical pellets are investigated as a more robust alternative. Methacholine is very hygroscopic and should therefore not be exposed to a high relative humidity. The methacholine particles leaving the Twincer ™ had an appropriate particle size distribution for inhalation. However, inhaler retention was high and should be reduced by controlling processing and storage conditions. Conclusions: Dry powder adenosine and methacholine seem promising alternatives for nebulisation. Methacholine must be handled under dry conditions. The highest doses of adenosine require further fine tuning.

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