title: Oral bioavailability in pigs of a miconazole/hydroxypropyl-gamma-cyclodextrin/L-tartaric acid inclusion complex produced by supercritical carbon dioxide processing.
abstract: The objective of this study was to determine the pharmacokinetic parameters of miconazole after oral administration of a miconazole/hydroxypropyl-gamma-cyclodextrin(HPgammaCD)/L-tartaric acid inclusion complex produced by supercritical carbon dioxide processing. The pharmacokinetics of the miconazole ternary complex (CPLX), of the corresponding physical mixture (PHYS), and of miconazole alone (MICO) were compared after oral administration. Six mixed-breed pigs received each formulation as a single dose (10 mg miconazole/kg) in a crossover design. Miconazole plasma concentrations were determined by a high-performance liquid chromatography method. Preliminary in vitro dissolution data showed that CPLX exhibits a faster and higher dissolution rate than either PHYS or MICO. Following CPLX oral administration, mean area under the plasma concentration curve (AUC(0-infinity)) for miconazole was 95.0 +/- 55.8 microg/min/mL, with the peak plasma concentration (C(max) 0.59 +/- 0.39 microg/mL) at 19.30 minutes. The AUC(0-infinity) and C(max) values were significantly higher than those after oral administration of PHYS (AUC(0-infinity) 38.5 +/- 12.7 microg/min/mL and C(max) 0.24 +/- 0.08 microg/mL; P < .1) and of MICO (AUC(0-infinity) 24.1 +/- 14.0 microg/min/mL and C(max) 0.1 +/- 0.05 microg/mL; P < .1). There were also significant differences between PHYS and MICO (P < .1). The results of the study indicate that CPLX shows improved dissolution properties and a higher relative oral bioavailability compared with PHYS and MICO.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Liege, CHU-Tour 4, Bat B36, Avenue de l'Hopital, 1, B-4000 Liege 1, Belgium. v.barillaro@ulg.ac.be
authors.forename: Valéry
authors.initials: V
authors.lastname: Barillaro
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
authors.forename: Luc
authors.initials: L
authors.lastname: Delattre
authors.forename: Géraldine
authors.initials: G
authors.lastname: Piell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002245:Carbon Dioxide; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D045424:Complex Mixtures; D005260:Female; D008297:Male; D008825:Miconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012995:Solubility; D034421:Sus scrofa; D013644:Tartrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D002214:Capsules; D045424:Complex Mixtures; D013644:Tartrates; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D002245:Carbon Dioxide; D008825:Miconazole; C029768:tartaric acid