In-vitro studies of betamethasone/cyclodextrin inclusion complexes

The interaction of Betamethasone (BMTZ) with different types of cyclodextrins (CD) was investigated. The effects of the types and concentration of CDs, as well as temperature on the inclusion behavior were also investigated. Different techniques were used in this investigation including phase solubility diagram (PSD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), H-1 -NMR and molecular mechanics (MM). PSD results indicated that the tendency of BMTZ to bind to CDs follows the order gamma-CD < alpha-CD < HP-beta-CD < beta-CD. This provides indications that size fit plays an important role on the inclusion complexation process. The thermodynamic parameters of the inclusion complexes under investigation were calculated. The negative entropy change indicated that con-formational changes were the dominant compared to the release of water solubility for the CD cavity and these formed an ice-burg structure around the BMTZ. MM study revealed that the dominant driving force of the inclusion complexation is the electrostatic energy. The DSC and SEM confirmed the for-mation of inclusion complex in the solid state.