title: Supercritical fluids crystallization of budesonide and flunisolide.
abstract: OBJECTIVE
  Budesonide and flunisolide anhydrate were crystallized using the solution enhanced dispersion by supercritical fluids (SEDS) technique. The aim was to investigate the possibility of preparing different pure polymorphs.
  
  
  METHODS
  0.25% w/v solutions of each drug were prepared from acetone and methanol. Operating conditions were 40-80 degrees C and 80-200 bars. The flow rate of drug solution was 0.3 mL/min and that of CO2 was 9-25 mL/min. Sample characterizations included differential scanning calorimetry, X-ray powder diffraction, variable temperature X-ray diffraction, scanning electron microscopy, and solubility studies.
  
  
  RESULTS
  The particle morphology of budesonide was dependent on the nature of the solvent. SEDS processing of flunisolide with acetone at 100 bars resulted in the formation of polymorphic mixtures at 80 degrees C and a new polymorph III at 60 C and 40 degrees C. With methanol at 100 bars another new polymorph IV was formed with different particle morphology at 80 degrees C and a polymorphic mixture at 60 degrees C.
  
  
  CONCLUSIONS
  Using the SEDS, microparticles of crystalline budesonide were prepared and new polymorphs of flunisolide were produced. Particle characteristics were controlled by the temperature, pressure and relative flow rates of drug solution and CO2.
authors.affiliation: Department of Pharmacy, Uppsala University, Sweden.
authors.forename: Sitaram P
authors.initials: SP
authors.lastname: Velaga
authors.forename: Rolf
authors.initials: R
authors.lastname: Berger
authors.forename: Johan
authors.initials: J
authors.lastname: Carlfors
mesh_terms: D019819:Budesonide / Q000737:chemistry*; D003460:Crystallization; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D012997:Solvents; D005446:Fluocinolone Acetonide; D019819:Budesonide; C007734:flunisolide