Improvement of water solubility and dissolution rate of ursodeoxycholic acid and chenodeoxycholic acid by complexation with natural and modified β-cyclodextrins

The inclusion complexes of ursodeoxycholic and chenodeoxycholic acid with β-cyclodextrin, heptakis-(2,6-di-O-methyl)-β-cyclodextrin and soluble polymerized β-cyclodextrin were investigated in solution (¹H-MMR spectrometry) and solid state (FT-IR spectroscopy and differential scanning calorimetry). Stability constants were determined at pH 7.4 and different temperatures and consequently thermodynamic parameters were obtained. All cyclodextrins are able to increase water solubility of the bile acids, particularly polymerized β-cyclodextrin. All complexes show high dissolution rate at 37°C and pH 1.1 and in particular freeze-dried complexes.