Insights into DPI sensitivity to humidity and its correlation to formulation physicochemical characteristics: a temporal study using two commercial budesonide products
J T Pinto1, S Radivojev1,2, E Fröhlich1,2 & A Paudel1,3
1Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, Graz, 8010, Austria
2Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, Graz, 8010, Austria
3Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, Graz, 8010, Austria
Summary
Dry powder inhalers (DPIs) can present different resistances to humidity. Considering that patients do not necessarily store their inhalers as recommended, the present study aims to evaluate the impact of different storage conditions (25ºC/ 65% RH and 22ºC/ >90% RH) on the physicochemical characteristics of two budesonide dry powder inhalers, namely Easyhaler® and Novolizer®. Both formulations are composed of a mixture of drug (ca. 4 wt %) and α-lactose monohydrate. Easyhaler® powders were found to contain larger coarse excipient particles as well as a higher fraction of fines when compared to Novolizer®. Moreover, it was possible to identify distinct trends with respect to the impact of storage on the two products. It was evident that at >90% RH, the kinetics of change in the physicochemical characteristics of the formulations were accelerated. Particularly, particle size distribution of Easyhaler® was notably impacted by storage. While, only subtle, temporary differences could be identified in the solid-state and particle size of Novolizer®. The encountered changes in physicochemical properties and consequent in-vitro aerodynamic performance correlated well with the already documented higher sensitivity of Easyhaler® to humidity than Novolizer®. This demonstrated that different formulation strategies can have distinct impacts on dry powders sensitivity to humidity.
