Interaction of diclofenac sodium with β- and hydroxypropyl-β-cyclodextrin in solution

The formation of inclusion compounds of diclofenac sodium with beta- and hydroxypropyl-beta-cyclodextrins was studied in solution by phase solubility techniques and by H-1-NMR spectroscopy. Phase solubility diagrams revealed the formation of a 1/1 complex with both cyclodextrin derivatives in simulated gastric juice pH 1.2, with a similar stability constant, i.e. 100.6 M-1 for beta-cyclodextrin and 115.8 M-1 for hydroxypropyl-beta-cyclodextrin. The continuous variation method was utilized to elucidate the stoichiometry determine the formation of complex with 1/1 and 1/2 drug/cyclodextrin ratio in deuterated water. Solid inclusion complexes were obtained by freeze-drying. X-ray diffractometry and differential scanning calorimetry showed differences between the complexes and their corresponding physical mixture and individual components. The solubility of diclofenac sodium increased significantly in the presence of cyclodextrins. Enhancement was better front the beta-cyclodextrin systems.