Efficacy of a new ketoconazole bioadhesive vaginal tablet on Candida albicans

• Published in: Farmaco (Società chimica italiana : 1989) 2004-02, Vol.59 (2), p.163-167
• Main Authors: Karasulu, H.Yeşim, Hilmioğlu, Süleyha, Metin, Dilek Y, Güneri, Tamer
• Format: Article
• Language: English
• Subjects: Adhesives; Administration, Intravaginal; Algorithms; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacology; Bioadhesive; Candida albicans; Candida albicans - drug effects; Chemistry, Pharmaceutical; Ketoconazole; Ketoconazole - administration & dosage; Ketoconazole - pharmacology; Kinetics; Microbial Sensitivity Tests; Minimum inhibitory concentration; Solubility; Tablets
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/j.farmac.2003.11.018

To develop more effective treatment for vaginal candidasis, ketoconazole (KTZ) was formulated in bioadhesive tablet formulations that increase the time of contact of drug with the vaginal mucosa. The bioadhesive vaginal tablets delivery of KTZ was prepared by direct compression of sodium carboxymethyl cellulose or polyvinylpyrrolidone or hydroxypropylmethyl cellulose (HPMC-E 50). Dissolution studies of bioadhesive tablets and commercial ovules were carried out with a new basket method (horizontal rotating basket). In vitro, a good sustained release action was obtained with bioadhesive tablets containing 1:1 and 1:2 drug/polymer ratio using HPMC-E 50. These bioadhesive tablets containing 400 mg of KTZ showed a zero-order drug release kinetic. KTZ solutions at increasing concentrations (0.16, 0.33, 0.5 and 0.66 mg/ml) were prepared for microbiological trials. These concentrations correspond to 25%, 50%, 75% and 100% of KTZ released from bioadhesive tablets, respectively. Yeast mixture was mixed with each concentration of KTZ at ratio of 1:10. One hundred microliters of this mixture was transferred in 900 μl liquid Sabouraud medium after a certain time interval for each concentration of KTZ and incubation at 37 °C for 24 h. Then this culture streaked onto Sabouraud-dextrose–agar plates, which were incubated at 37 °C for 48 h. The 0.16 and 0.33 mg/ml concentrations of KTZ showed fungistatic effect in 120 min. The 0.5 mg/ml concentration of KTZ was fungistatic in 90 and 120 min; and the 0.66 mg/ml concentration of the drug was fungistatic in 120 min as well as in 180 min. It was found that, in vitro antifungal activity of KTZ was dependent on its concentration and contact time with yeast cells. These results indicated that a new bioadhesive vaginal tablet formulations might be further developed for safe convenient and effective treatment of vaginal candidasis.