title: Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide.
abstract: OBJECTIVE
  The present study describes the crystal structure changes of gamma-cyclodextrin (gamma-CD) during the solution enhanced dispersion by supercritical fluids (SEDS) process and its effect on dissolution behaviour of complexed budesonide.
  
  
  METHODS
  gamma-CD solution (10 mg/ml in 50% ethanol) was pumped together with supercritical carbon dioxide through a coaxial nozzle with or without a model drug, budesonide (3.3 mg/ml). The processing conditions were 100 b and 40, 60 or 80 degrees C. gamma-CD powders were characterised before and after vacuum-drying (2-3 days at RT) with XRPD, SEM and NMR. Budesonide/gamma-CD complexation was confirmed with DSC and XRPD. The dissolution behaviour of complexed budesonide was determined in aqueous solution (1% gamma-CD, 37 degrees C, 100 rpm).
  
  
  RESULTS
  During the SEDS process (100 b, 40 and 60 degrees C), gamma-CD and budesonide/gamma-CD complexes crystallized in a tetragonal channel-type form. The vacuum-drying transformed crystalline gamma-CD into amorphous form while the complexes underwent a tetragonal-to-hexagonal phase transition. The increase in the processing temperature decreased the crystallinity of gamma-CD. At 80 degrees C, amorphous gamma-CD was obtained while the complexes crystallized in a hexagonal channel-type form. The dissolution behaviour of budesonide/gamma-CD complexes was dependent on their crystal structure: the tetragonal form dissolved faster than the hexagonal form.
  
  
  CONCLUSIONS
  The crystal structure of gamma-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.
authors: Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland. tarja.toropainen@uku.fi
authors: Tarja
authors: T
authors: Toropainen
authors: Teemu
authors: T
authors: Heikkilä
authors: Jukka
authors: J
authors: Leppänen
authors: Laura
authors: L
authors: Matilainen
authors: Sitaram
authors: S
authors: Velaga
authors: Pekka
authors: P
authors: Jarho
authors: Johan
authors: J
authors: Carlfors
authors: Vesa-Pekka
authors: VP
authors: Lehto
authors: Tomi
authors: T
authors: Järvinen
authors: Kristiina
authors: K
authors: Järvinen
mesh_terms: D019819:Budesonide / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D012995:Solubility; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D047408:gamma-Cyclodextrins; D002245:Carbon Dioxide; D019819:Budesonide; C023792:gamma-cyclodextrin