Cyclodextrin/diacerein inclusion complex: a tool for therapeutic drug delivery

Diacerein (DAR) is a pro-drug that undergoes hydrolysis into Rhein (Rh); complexation with Cyclodextrins has been suggested to modulate DAR degradation rate. In this work, the effect of hydroxypropyl derivate of β-Cyclodextrin (HPβCD) complexation on the DAR hydrolysis has been investigated. As for DAR stability in cyclodextrin complexes, a decrease in the hydrolysis rate constant (Kc) with increasing cyclodextrin concentration has been observed (0.23 h-1 vs 0.11 h-1 for free drug and for 100 mM HPβCD, respectively). A stability constant (Xst) of DAR/HPpCD complex of 50 M-1 was obtained by the kinetic data. Such a value was compared with those obtained by Benesi-Hildebrand equation applied to spectroscopic measurements, HPLC method and Phase Solubility studies. The influence of complexation technique on aqueous solubility and dissolution rate profiles was also assessed. For this purpose solid complexes are prepared by freeze drying, co-evaporation, and kneading techniques. The results, obtained by UV-Vis spectroscopy analysis, have been compared with those obtained for the physical mixture. Eventually, selective physicochemical determinations based on differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to characterize the complexes. © 2011, AIDIC Servizi S.r.l.