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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Nyckelord

γ-cyclodextrin

Amorphicity

Budesonide

Channel structure

Complex

Dissolution

Hexagonal

SEDS

Supercritical fluids

Tetragonal

PHARMACY

FARMACI

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