Preparation of budesonide/γ‐cyclodextrin complexes in supercritical fluids with a novel SEDS method

The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single‐step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and γ‐cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80°C. SEDS‐processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% γ‐CD aqueous solution. Solid, white budesonide/γ‐CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60°C) the yield of the powder was 65 ± 12% with 0.14 ± 0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93 ± 2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41 ± 10%) and SEDS‐processed budesonide without CD (61 ± 3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single‐step process.