A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis.
The use of dental varnish for therapeutic purposes has been reported for fluoride or antibacterial drugs. Our objectives were to develop a sustained-release varnish containing an antifungal drug (clotrimazole) for topical application and to evaluate the release rate of the drug in human saliva in comparison with an available commercial troche and their acceptance by healthy volunteers. Following in vitro optimization of the release rate from the varnish, we have embarked on a crossover comparative study assessing the oral sensations and pharmacokinetics of a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed for clotrimazole concentration by high performance liquid chromatography analysis. The volunteers' evaluation of the varnish and troche (taste, other sensory changes, convenience, and oral suitability) were recorded. At all time points, salivary clotrimazole concentrations were higher, and the terminal half-life was significantly prolonged in the varnish group in comparison to the control group. This can be attributed to continuous release of clotrimazole from the varnish formulation. The duration of the drug over the minimal inhibitory concentration, following application of the varnish, was more than threefold longer than following administration of the troche. The developed sustained-release varnish can be applied in patients at a lower frequency than troches, thus, achieving higher patient compliance and efficacy. This novel varnish application can serve as the basis for a new treatment approach to oral candidiasis, a very common chronic opportunistic infection with improved clinical outcome.
Czerninski
Rakefet
R
The Department of Oral Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. rakefetc@hadassah.org.il
Sivan
Sagi
S
Steinberg
Doron
D
Gati
Irith
I
Kagan
Leonid
L
Friedman
Michael
M
D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002180:Candidiasis, Oral / Q000188:drug therapy*; D003022:Clotrimazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D010150:Paint; D010349:Patient Compliance; D012463:Saliva / Q000737:chemistry; D013607:Tablets; D013649:Taste / Q000187:drug effects; D055815:Young Adult
D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D003022:Clotrimazole