Impact of Budesonide Particle Shape on Uptake by Respiratory Cells and Macrophages 

Sarah Zellnitz¹, Marie-Theres Müller^1,2 & Eleonore Fröhlich^1,2

¹Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 21a/II, Graz, 8010, Austria

²Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, Graz, 8010, Austria

Summary

For administering active pharmaceutical ingredients (APIs) to the lung, a particle size of 1-5 µm is desirable. Consequently, during dry powder inhaler (DPI) formulation development usually a processing/size reduction step of the API is needed. The most common processing technique is milling, however, spray drying has shown to be a suitable alternative. Both techniques lead to inhalable sized particles but other properties like shape and/or solid-state can vary. Previous work on salbutamol sulphate has shown that for highly water soluble APIs the distinct particle properties generated during processing do not affect the dissolution behaviour. However, cellular uptake and permeability as well as in vitro aerosolization performance could be influenced ^[1]. In order to get more insight on the impact of particle properties (especially the shape, on the biological action of the inhaled particles) budesonide, an API with lower solubility, was chosen as model API for the present work. Jet milled and spray dried budesonide formulations were evaluated for dissolution, permeation, and preferential uptake by epithelial cells compared to macrophages. Spray dried spherical particles showed lower respirable fractions and dissolved slower compared to jet milled needle/rod shaped particles. However, permeability and cellular uptake were higher for the spray dried API. This could possibly be due to the action of one or more uptake mechanisms; i.e. passive diffusion and/or pinocytosis.