Preparation, characterization, and evaluation of miconazole-cyclodextrin complexes for improved oral and topical delivery

J Pharm Sci. 1998 Apr;87(4):425-9. doi: 10.1021/js970361l.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Adult
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacokinetics
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Cyclodextrins / chemistry*
  • Drug Carriers
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Hairless
  • Miconazole / administration & dosage*
  • Miconazole / chemistry
  • Miconazole / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Solubility

Substances

  • Antifungal Agents
  • Cyclodextrins
  • Drug Carriers
  • Miconazole