Crystal Structure Changes of γ -cyclodextrin After the SEDS Process in Supercritical Carbon Dioxide Affect the Dissolution Rate of Complexed Budesonide.

Abstract Purpose  The present study describes the crystal structure changes of γ-cyclodextrin (γ-CD) during the solution enhanced dispersion by supercritical fluids (SEDS) process and its effect on dissolution behaviour of complexed budesonide. Materials and Methods  γ-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 80C. γ-CD powders were characterised before and after vacuum-drying (2–3 days at RT) with XRPD, SEM and NMR. Budesonide/γ-CD complexation was confirmed with DSC and XRPD. The dissolution behaviour of complexed budesonide was determined in aqueous solution (1% γ-CD, 37C, 100 rpm). Results  During the SEDS process (100 b, 40 and 60C), γ-CD and budesonide/γ-CD complexes crystallized in a tetragonal channel-type form. The vacuum-drying transformed crystalline γ-CD into amorphous form while the complexes underwent a tetragonal-to-hexagonal phase transition. The increase in the processing temperature decreased the crystallinity of γ-CD. At 80C, amorphous γ-CD was obtained while the complexes crystallized in a hexagonal channel-type form. The dissolution behaviour of budesonide/γ-CD complexes was dependent on their crystal structure: the tetragonal form dissolved faster than the hexagonal form. Conclusions  The crystal structure of γ-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions. [ABSTRACT FROM AUTHOR]