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

Abstract

The formation of inclusion compounds of diclofenac sodium with β- and hydroxypropyl- β -cyclodextrins was studied in solution by phase solubility techniques and by 1H-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·' for β-cyclodextrin and 115.8 M·' for hydroxypropyl- β -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 from the β-cyclodextrin systems