Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis

• Published in: Journal of controlled release 2002-07, Vol.82 (1), p.39-50
• Main Authors: Yun Chang, Jung, Oh, Yu-Kyoung, Soo Kong, Hak, Jung Kim, Eun, Deuk Jang, Dong, Taek Nam, Ki, Kim, Chong-Kook
• Format: Article
• Language: English
• Subjects: Adhesives - chemistry; Administration, Intravaginal; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Antifungal Agents - toxicity; Biological and medical sciences; Candida albicans - drug effects; Candidiasis, Vulvovaginal - drug therapy; Candidiasis, Vulvovaginal - microbiology; Cell Line; Cell Survival - drug effects; Clotrimazole; Clotrimazole - chemistry; Clotrimazole - pharmacology; Clotrimazole - therapeutic use; Clotrimazole - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Female; Gels; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Microbial Sensitivity Tests; Mucoadhesive thermosensitive gels; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Rheology; Temperature; Time Factors; Vagina - pathology; Vaginal candidasis; Vaginal delivery; Vaginitis - drug therapy; Vaginitis - microbiology
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(02)00086-X

To develop more effective treatment for vaginal candidasis, clotrimazole (CT) was formulated in mucoadhesive thermosensitive gels (MTG). Several MTG formulations composed of poloxamers (P) 407, 188, and polycarbophil (PC) were prepared. P188 and PC increased the mucoadhesiveness but reduced the syringebility of liquid forms of the gels. Based on the balance between the mucoadhesiveness and syringebility, MTG composed of P407/P188/PC (15/15/0.2 or 15/20/0.2) were further studied. Of the two MTG, the formulation with 15% of P188 gelled at higher temperature and revealed lower elastic modulus. In vitro, sustained release of CT from MTG was observed. In vivo antifungal activity of CT, tested against Candida albicans vaginitis in female rats, was significantly prolonged after vaginal delivery using MTG. At 10 days post-dose, the c.f.u. of C. albicans was more than 10 4-fold decreased in MTG-treated groups. Moreover, the vaginal delivery of CT in MTG enhanced the viability of epithelial cells without affecting the morphology of vaginal mucosa. These results indicate that CT-containing vaginal MTG might be further developed for safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.