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.
Tenjarla
S
S
Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341, USA. tenjarla@sri.org
Puranajoti
P
P
Kasina
R
R
Mandal
T
T
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008825:Miconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000935:Antifungal Agents; D003505:Cyclodextrins; D004337:Drug Carriers; D008825:Miconazole