Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide.
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.
Toropainen
Tarja
T
Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland. tarja.toropainen@uku.fi
Heikkilä
Teemu
T
Leppänen
Jukka
J
Matilainen
Laura
L
Velaga
Sitaram
S
Jarho
Pekka
P
Carlfors
Johan
J
Lehto
Vesa-Pekka
VP
Järvinen
Tomi
T
Järvinen
Kristiina
K
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*
D047408:gamma-Cyclodextrins; D002245:Carbon Dioxide; D019819:Budesonide; C023792:gamma-cyclodextrin