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 cyclodextrins (CDs). The apparent K1:1 values calculated from the phase solubility diagrams of gamma-CD, hydroxypropyl-beta-CD, alpha-CD, hydroxyethyl-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 freeze-drying and kneading and characterized by UV spectroscopy, differential scanning calorimetry, and electron microscopy. The dissolution rate increased to 28-255-fold and the solubility to 9-55-fold. Oral bioavailability in rats increased to 2.3-fold by complexation with hydroxypropyl-beta-CD. Human cadaver skin retained 2.6-fold more drug from the miconazole/alpha-CD complex and hairless mice skin retained 8.4-fold more drug from the HP-beta-CD complex than from miconazole solution alone in 24 h.