Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide
2007 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 24, no 6, 1058-1066 p.Article in journal (Refereed) Published
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 80°C. 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, 37°C, 100 rpm). Results. During the SEDS process (100 b, 40 and 60°C), 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 80°C, 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.
Place, publisher, year, edition, pages
2007. Vol. 24, no 6, 1058-1066 p.
γ-cyclodextrin, Amorphicity, Budesonide, Channel structure, Complex, Dissolution, Hexagonal, SEDS, Supercritical fluids, Tetragonal
IdentifiersURN: urn:nbn:se:uu:diva-11409DOI: 10.1007/s11095-006-9227-7ISI: 000246619700003PubMedID: 17385023OAI: oai:DiVA.org:uu-11409DiVA: diva2:39178