Preparation and physico-chemical study of inclusion complexes between idebenone and modified β-cyclodextrins

The inclusion properties of modified β-cyclodextrins (trimethyl-β-cyclodextrin, dimethyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin) towards idebenone were compared with natural β-cyclodextrin. The inclusion complexes were prepared by different methods (coprecipitation, kneading, and freeze-drying) and characterized by differential scanning calorimetry, X-ray diffractometry, UV, CD and NMR spectroscopy. The results obtained by CD and NMR spectroscopy indicate a different orientation of idebenone in dimethyl-β-cyclodextrin with respect to other cyclodextrins. Stability constants of the complexes were determined in water at various temperatures and consequently thermodynamic parameters were obtained. All cyclodextrins are able to significantly increase the water solubility of idebenone, particularly dimethyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin, as a result of complexation. Consequently, they enhance the dissolution rate of the complexed drug compared to the free drug.