Application of Supercritical Carbon Dioxide for the Preparation of Drug-Cyclodextrin Inclusion Compounds

Inclusion complexes of drugs into cyclodextrins (CDs) can be obtained at the solid state by means of supercritical dioxide (SCCO 2 ). A successful inclusion with a yield >98.5% has been achieved with piroxicam and β-CD. The temperature and the time of exposure to SCCO 2 have a significant effect on the inclusion yield while the pressure has a negative effect. However, there is a strong interaction between temperature and pressure and this interaction has a positive influence. The molar ratio piroxicam-β-CD and the addition of ternary alkaline agents were also found to be significant factors. The dissolution rate of the complexes formed using SCCO 2 was found to be significantly higher than that of the physical mixture. Inclusion complexes have also been obtained with miconazole treating mixtures of miconazole, CDs and citric acid by SCCO 2 . This new technique of inclusion of poorly soluble drugs into CDs allows the preparation of solid complexes without using organic solvents and thus without residues.