Ketoconazole In Situ Gel Versus Terconazole Cream for Treatment of Vaginal Candidiasis

terconazole- Terconazole, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of Terconazole. Mammalian cell demethylation is less sensitive to Terconazole inhibition Terconazole exhibits antifungal activity in vitro against Candida albicans and other Candida species. The MIC (maximum insufflation capacity values of Terconazole against most Lactobacillus spp. typically found in the human vagina were ≥128 mcg/mL; therefore these beneficial bacteria are not affected by drug treatment.

Terconazole Vaginal cream, 80 mg are indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As this product is effective only for vulvovaginitis caused by the genus Ketoconazole is a broad- spectrum antimycotic agent that can be used orally or topically in the treatment vulvovaginal candidiasis and other fungal infections Candida is the second most common cause of vaginal infections. Candida albicans is responsible for 80 to 92% of episodes of vulvovaginal candidiasis . The rest are due to non-albicans Candida species, the most common of which are C. glabrata and C. tropicalis. Sporadic attacks of vulvovaginal candidiasis usually occur without an identifiable precipitating factor. The risk of vulvovaginal candidiasis may be higher in women with uncontrolled diabetes, who use oral contraceptives containing high levels of estrogen or taking antibiotics.

In situ gelling systems refer to polymer solutions which can be administered as liquid, and undergo a phase transition to semisolid gel upon exposure to physiological environments. Stimuli- sensitive hydrogels are those hydrogels, which undergo reversible volume phase - transition or sol - gel phase transition in response to external physical stimuli such as (temperature) or chemical stimuli as (ions).The most commonly used thermoreversible gels are those prepared from the pluronic block copolymers . The principle advantage of in situ forming gels is the possibility of administering accurate and reproducible quantities, in contrast to already gelled formulation . Several in situ gel forming systems have been developed to prolong the residence time of a drug and improve the bioavailability and control the drug release by changing the gel structure in response to environmental stimuli . These systems provide simplicity and safety in in vivo situations . They are handled in the liquid state before their delivery, which is likely to facilitate their use and to increase the surface of contact with the mucous membrane. The flow properties of semi-solid vaginal dosage forms might be of use to predict the spreading and coating of the formulations over the vaginal epithelia . When the preparation is given as liquid, this will give better spreading and coating of vaginal surfaces than the gelled preparations, which have not the ability to cover all the surfaces and cannot reach to epithelial folds of the vagina. So, this study aimed to formulate ketoconazole in a new vaginal mucoadhesive form "In situ gel" and it is designed to achieve the following objectives:

• Formulation and evaluation of in situ-forming vaginal gels of ketoconazole.
• Clinical assessment of the prepared vaginal ketoconazole in situ gels on women suffering from vaginal candidiasis.

Materials and Methods: