Formulation Development and Evaluation of in Situ Gel for Vaginal Drug Delivery of Anti Fungal Drug

The aim of the present study was to formulate and evaluate nystatin containing thermosensitive mucoadhesive gel for vaginal drug delivery to achieve prolonging the residence time, sustained drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance in the treatment for vaginal candidiasis. Here nystatin (1%) as a model drug. A 3 full factorial design was employed with two polymers: Pluronic F 68 and HPMC K4M as independent variables used in combination with Pluronic F 127. Vaginal gel was prepared by “cold method.” Vaginal gel using thermosensitive polymer, pluronic F127(15%w/v) and pluronic F68 along with mucoadhesive polymers such as HPMC K4M. The drug polymer compatibility was studied using FTIR and DSC. The prepared formulations were evaluated for parameters such as gelation temperature, viscosity, mucoadhesive strength, gel strength drug release and antifungal activity. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 33–36 °C. HPMC K4M loading showed a positive effect on mucooadhesion force and gel strength and was also found helpful in sustain the release rate of the drug. The developed formulations had optimum viscosity, good bioadhesive strength and hence will have high retention property which is required for convenience at the site of application. Among the prepared formulations, one with the combination of pluronic F127(15%w/v), pluronic F68(15%w/v) and HPMC K4M(1%w/v) showed optimum gelation temperature, viscosity, bioadhesive strength, mucoadhesion force, antifungal activity with sustained drug release for 8 hrs. The optimized formulation (F5) showed insignificant change in physical property and drug content when stability testing was carried out at 40oC/75%RH for 1 months. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature and, mucoadhesion force. All the performed experiments confirm the applicability of thermosensitive and mucoadhesive In-situ gels as a novel delivery system for local therapy of vaginal candidiasis.