Inclusion compound formulation of hirsutenone with beta-cyclodextrin

Inclusion complexation with β-cyclodextrin (β-CD) was performed to improve the stability of hirsutenone (HST), a naturally occurring immunomodulator that is labile in aqueous solutions. HST-β-CD inclusion complexes were prepared using a solvent evaporation method. Briefly, solutions of HST (dissolved in isopropyl alcohol) and β-CD (dissolved in distilled water) were mixed and evaporated under vacuum by using a rotary evaporator. Phase solubility studies of the product revealed 1:1 or 1:2 complex formation, with an apparent stability constant of 249.2 M −1 . Differential scanning calorimetry showed a shift of endothermic peaks and nuclear magnetic resonance spectra displayed shift changes in H-3,5,6 protons, located inside the β-CD cavity, in inclusion complexes. These data provided strong evidence for inclusion complex formation. Characterization using infrared spectroscopy was hindered because of interfering β-CD vibrations. Inclusion complex stability was evaluated in the solid and aqueous solution states. Rate constants (×10 −2 , day −1 ) of HST and HST-β-CD were 13.2 and 9.79, respectively, in an aqueous solution at 25 °C; the corresponding values in the solid state were 0.14 and 0.18. The present study therefore showed successful formation of HST-β-CD, but the stability of HST within this inclusion compound was not markedly improved.