Preparation of budesonide/γ‐cyclodextrin complexes in supercritical fluids with a novel SEDS method  Tarja Toropainen, Sitaram Velaga, Teemu Heikkilä, Laura Matilainen, Pekka Jarho, Johan Carlfors, Vesa‐Pekka Lehto, Tomi Järvinen, Kristiina Järvinen  Journal of Pharmaceutical Sciences  Volume 95, Issue 10, Pages 2235-2245 (October 2006) DOI: 10.1002/jps.20702 Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 1 Schematic representation of the SEDS apparatus. (a) The coaxial nozzle (1) is connected to particle formation chamber (2) in a thermostated oven (3). (b) The solvent connections before the coaxial nozzle: conventional method (left) and modified method (right). Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 2 DSC thermograms of unprocessed and SEDS‐processed powders: unprocessed micronised budesonide (I), SEDS‐processed budesonide (100 bar, 60°C) (II), SEDS‐processed budesonide (100 bar, 80°C) (III), unprocessed physical mixture of budesonide and γ‐cyclodextrin (IV), precipitated budesonide/γ‐cyclodextrin complexes (V) and SEDS‐processed budesonide/γ‐cyclodextrin complexes (prepared with conventional method at 100 bar, 60°C) (VI). Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 3 Dissolution profiles of unprocessed micronised budesonide (black squares), SEDS‐processed budesonide (100 bar, 60°C) (black circles), unprocessed physical mixture of budesonide and γ‐cyclodextrin (grey triangles), precipitated budesonide/γ‐cyclodextrin complexes (black triangles) and SEDS‐processed budesonide/γ‐cyclodextrin complexes: conventional method 100 bar, 60°C (white squares) and modified method 100 bar, 60°C (white circles) (mean; n = 3–5). Data from Table 3. Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 4 X‐ray powder diffractograms of unprocessed micronised budesonide (a), unprocessed γ‐cyclodextrin (b), unprocessed physical mixture of budesonide and γ‐cyclodextrin (c), precipitated budesonide/γ‐cyclodextrin complexes (d), SEDS‐processed budesonide/γ‐cyclodextrin complexes (prepared with conventional method at 100 bar, 60°C) (e), SEDS‐processed budesonide/γ‐cyclodextrin complexes (prepared with modified method at 100 bar, 60°C) (f). Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 5 SEM images of unprocessed, micronised budesonide (a), SEDS‐processed budesonide/γ‐cyclodextrin complexes; conventional method 100 bar, 60°C (b) and modified method 100 bar, 60°C (c). Image scale bar = 20 µm; inset scale bar = 5 µm. Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions

Figure 6 Effect of SEDS processing conditions on the complexation efficiency between budesonide and γ‐cyclodextrin. Journal of Pharmaceutical Sciences 2006 95, 2235-2245DOI: (10.1002/jps.20702) Copyright © 2006 Wiley‐Liss, Inc. Terms and Conditions