Impact of salbutamol sulphate particle properties on
biological effects in the lung
S Zellnitz1, Lisa Zellnitz1, Eva Roblegg1,2 & Eleonore Fröhlich1,3
1Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 21a/II, Graz, Austria
2Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University of Graz, 8010, Austria
3Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, Graz, 8010, Austria
Generating inhalable sized particles (1-5 µm) involves a particle processing step; most commonly milling but spray drying has shown to be a suitable alternative. Besides the particle size, these distinct particle processing techniques may impact other particle properties, like shape and solid-state. The model drug chosen for the present study is salbutamol sulphate (SS) and previous work has shown that spray-drying of SS leads to spherical shaped predominantly amorphous particles whereas jet-milling of SS maintains the needle like shape and the crystallinity of the raw material. Moreover, the in vitro respirable fraction was lower for the spray-dried SS compared to the jet-milled SS. The aim of the present study was to investigate whether particle properties, especially shape, changes the biological action of the inhaled particles. Therefore, the two formulations were evaluated regarding dissolution, permeation and preferential uptake by epithelial cells compared to macrophages.
Jet-milled needle like, predominantly crystalline, particles resulted in higher respirable fractions, lower apparent permeability coefficient (Papp) values, and low uptake in macrophages compared to the spherically shaped, predominantly amorphous, spray–dried particles with lower respirable fraction, higher epithelial permeability and higher uptake by macrophages. The differently engineered particles showed similar dissolution behaviour and dissolution was almost complete after 2 minutes, which makes a prominent influence of phagocytosis rather unlikely. It is possible that the crystalline particles after partial dissolution were in the range for preferential active uptake by alveolar epithelial cells. Time dependent studies and the use of API with lower solubility will be performed to get more insight.