title: Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method.
abstract: The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 degrees C) the yield of the powder was 65+/-12% with 0.14+/-0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93+/-2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41+/-10%) and SEDS-processed budesonide without CD (61+/-3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, F1-70211 Kuopio, Finland. tarja.toropainen@uku.fi
authors.forename: Tarja
authors.initials: T
authors.lastname: Toropainen
authors.forename: Sitaram
authors.initials: S
authors.lastname: Velaga
authors.forename: Teemu
authors.initials: T
authors.lastname: Heikkilä
authors.forename: Laura
authors.initials: L
authors.lastname: Matilainen
authors.forename: Pekka
authors.initials: P
authors.lastname: Jarho
authors.forename: Johan
authors.initials: J
authors.lastname: Carlfors
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Tomi
authors.initials: T
authors.lastname: Järvinen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
mesh_terms: D019819:Budesonide / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011208:Powders; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014961:X-Ray Diffraction; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D011208:Powders; D012997:Solvents; D047408:gamma-Cyclodextrins; D002245:Carbon Dioxide; D000431:Ethanol; D019819:Budesonide