A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole
Journal Title: The AAPS Journal - Year 2003, Vol 5, Issue 1
Abstract
The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-β-cyclodextrin (HPβCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPβCD. After pH adjustment, the itraconazole/HPβCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPβCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.
Authors and Affiliations
Marc Francois, Eric Snoeckx, Peter Putteman, Fons Wouters, Eddy De Proost, Urbain Delaet, Jef Peeters, Marcus E. Brewster
Keywords
Related Articles
- EP ID EP681963
- DOI 10.1208/ps050105
- Views 83
- Downloads 0
Drug Absorption Modeling as a Tool to Define the Strategy in Clinical Formulation Development
This article inadvertently failed to include two of the theme issue guest editors. The complete listing of the guest editors is shown in this erratum.
Gum Arabic-Coated Magnetic Nanoparticles for Potential Application in Simultaneous Magnetic Targeting and Tumor Imaging
Magnetic iron oxide nanoparticles (MNP) coated with gum arabic (GA), a biocompatible phytochemical glycoprotein widely used in the food industry, were successfully synthesized and characterized. GA-coated MNP (GA-MNP) di...
2-Arachidonoylglycerol (2-AG) membrane transport: History and outlook
Only a few studies have addressed the transport of 2-arachidonoylglycerol (2-AG), a naturally occurring agonist for cannabinoid receptors. Based upon saturation kinetics, these early reports have proposed that 2-AG enter...
Measuring Endocannabinoid Hydrolysis: Refining our Tools and Understanding
Endocannabinoids (eCBs) are lipid transmitters that are released from membrane precursors in response to specific stimuli, activate cannabinoid receptors—the molecular targets of compounds produced by Cannabis sa...
Hepatic Metabolism and Disposition of Baicalein via the Coupling of Conjugation Enzymes and Transporters—In Vitro and In Vivo Evidences
Baicalein (Ba) was found to be subject to serious first-pass metabolism after oral administration. We previously revealed the important role of intestine in the low oral bioavailability of Ba. The present study aims to e...