PREPARATION, CHARACTERIZATION, AND EVALUATION OF MICONAZOLE-CYCLODEXTRIN COMPLEXES FOR IMPROVED ORAL AND TOPICAL DELIVERY

The solubility of miconazole in water increased in the presence of cyc lodextrins (CDs). The apparent K-1:1 values calculated from the phase solubility diagrams of gamma-CD, hydroxypropyl-beta-CD, alpha-CD, hydr oxyethyl-beta-CD, hydroxypropyl-gamma-CD, and beta-CD were 695 +/- 39. 6, 363 +/- 34.1, 333 +/- 18.5, 312 +/- 31.0, 305 +/- 27.6, and 293 +/- 17.6 M-1, respectively. Solid 1:1 molar complexes were prepared by fr eeze-drying and kneading and characterized by UV spectroscopy, differe ntial scanning calorimetry, and electron microscopy. The dissolution r ate increased to 28-255-fold and the solubility to 9-55-fold. Oral bio availability in rats increased to 2.3-fold by complexation with hydrox ypropyl-beta-CD. Human cadaver skin retained 2.6-fold more drug from t he miconazole/alpha-CD complex and hairless mice skin retained 8.4-fol d more drug from the HP-beta-CD complex than from miconazole solution alone in 24 h.