Multicomponent systems of econazole with hydroxyacids and cyclodextrins

The effect of the type of cyclodextrin (alpha-, beta-, gamma-, hydroxypropy l-beta -CD) and of hydroxyacid (tartaric, citric, gluconic, malic, lactic) on the solubility enhancement by multicomponent complexation of econazole, a poorly water soluble base-type drug, was studied. A synergistic effect wa s found in ternary systems, largely more effective than corresponding binar y complexes and salts. Moreover, the presence of a third component made eff ective the use of gamma -CD, which had no solubilizing power in binary syst ems. The solubilizing efficiency of multicomponent systems was not related to the solubilities of the corresponding salts or binary complexes. Phase-s olubility analysis at different temperatures was also used to investigate t he interaction of econazole with cyclodextrins, alone or in the presence of hydroxyacid. The best 1 : 1 : 1 molar ratio system was that with alpha -CD and malic acid which showed the best solubilizing power and the highest st ability constant of the ternary complex. Ternary alpha -CD products, prepar ed by co-grinding, co-evaporation or colyophilization, were characterized b y Differential Scanning Calorimetry and tested for dissolution properties. The higher solubilizing properties of multicomponent systems were reflected in better drug dissolution rates from their solid systems.