Crystal structure changes of γ-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide

• Published in: Pharmaceutical research 2007-06, Vol.24 (6), p.1058-1066
• Main Authors: TOROPAINEN, Tarja, HEIKKILÄ, Teemu, LEPPANEN, Jukka, MATILAINEN, Laura, VELAGA, Sitaram, JARHO, Pekka, CARLFORS, Johan, LEHTO, Vesa-Pekka, JARVINEN, Tomi, JÄRVINEN, Kristiina
• Format: Article
• Language: English
• Subjects: Amorphicity; Biological and medical sciences; Budesonide; Budesonide - chemistry; Carbon dioxide; Carbon Dioxide - chemistry; Channel structure; Complex; Crystal structure; Crystallography, X-Ray; Cyclodextrin; Dissolution; Drying; Ethanol; FARMACI; gamma-Cyclodextrins - chemistry; General pharmacology; Hexagonal; Medical sciences; Microscopy, Electron, Scanning; Molecular Structure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PHARMACY; Phase transitions; SEDS; Solubility; Supercritical fluids; Tetragonal; Vacuum; γ-cyclodextrin
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-006-9227-7

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. 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). 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. The crystal structure of gamma-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.