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

The formation of inclusion compounds of diclofenac sodium with beta- and hy droxypropyl-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 simula ted 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. T he 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-dry ing. X-ray diffractometry and differential scanning calorimetry showed diff erences between the complexes and their corresponding physical mixture and individual components. The solubility of diclofenac sodium increased signif icantly in the presence of cyclodextrins. Enhancement was better front the beta-cyclodextrin systems.