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 beta-Cyclodextrin (HP beta CD) complexation on the DAR hydrolysis has been investigated. As for DAR stability in cyclodextrin complexes, a decrease in the hydrolysis rate constant (K(c)) with increasing cyclodextrin concentration has been observed (0.23 h(-1) vs 0.11h(-1) for free drug and for 100 mM HP beta CD, respectively). A stability constant (K(st)) of DAR/HP beta CD 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.
Cyclodextrin/Diacerein Inclusion Complex: a Tool for Therapeutic Drug Delivery / Petralito, Stefania; Adriana, Memoli; Iacopo, Zanardi; Annesini, Maria Cristina; Valtertravagli,. - 24(2011), pp. 967-972. ((Intervento presentato al convegno 10th International Conference on Chemical and Process Engineering tenutosi a Florence, ITALY nel MAY 08-11, 2011. - CHEMICAL ENGINEERING TRANSACTIONS. [10.3303/cet1124162].
Cyclodextrin/Diacerein Inclusion Complex: a Tool for Therapeutic Drug Delivery
PETRALITO, Stefania;ANNESINI, Maria Cristina;
2011
Abstract
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 beta-Cyclodextrin (HP beta CD) complexation on the DAR hydrolysis has been investigated. As for DAR stability in cyclodextrin complexes, a decrease in the hydrolysis rate constant (K(c)) with increasing cyclodextrin concentration has been observed (0.23 h(-1) vs 0.11h(-1) for free drug and for 100 mM HP beta CD, respectively). A stability constant (K(st)) of DAR/HP beta CD 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.