Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes

• Diacerhein (DARh) is a prodrug of the IL-1 converting enzyme inhibitor Rhein (Rh).
• The interaction of DARh with HPβCD has been studied by molecular spectroscopy.
• Both the free and the complexed DARh can undergo hydrolysis to generate Rh.
• DARh and Rh have some coincident spectroscopic parameters.
• Accurate experimental and spectroscopic settings are essential parameters.

Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HPβCD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 °C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HPβCD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi–Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution.

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