DEVELOPMENT OF THERMOSENSITIVE GEL OF FLUCONAZOLE FOR VAGINAL CANDIDIASIS
Keywords:Fluconazole, Vaginal drug delivery, In-situ gel, Poloxamer, Candidiasis
Objective: The aim of the present study was to develop in-situ gelling formulations of Fluconazole (FCZ) using thermosensitive polymer for treatment of vaginal Candidiasis.
Methods: In-situ gelling formulations of FCZ (1 % w/w) were prepared with different concentrations of Poloxamer 407 (P 407, 15-20% w/w) using the cold dispersion method. Similarly, Â formulations were also prepared by adding mucoadhesive polymers like hydroxyethyl cellulose, Polycarbophil, Carbopol 974 and Hydroxypropyl methylcellulose E 50 LV (0.4 % w/w) to the P 407 formulations. These formulations were evaluated for appearance, clarity, pH, gelling ability, gelling time, gelling temperature, viscosity (in sol and gel forms), spreading time, ex-vivo mucoadhesion, in-vitro dissolution, morphological characteristics by SEM and in-vitro antifungal efficacy against Candida albicance. In-vivo vaginal irritation of developed formulation was assessed in New Zealand female rabbits.
Results: In-situ gelling formulation of FCZ, prepared using 18 % w/w P407 and 0.4 % hydroxyethyl cellulose, was optimized since this formulation was found to be clear, transparent, forming a quick and stable gel with shear thinning behaviour and excellent mucoadhesion. The developed formulation released 74.21% of FCZ after 8 h of dissolution in 5.2 pH citrate buffer. In-vitro antifungal activity against Candida albicance showed the stronger antifungal activity of formulation as compared to a marketed formulation. In-vivo vaginal irritation study in rabbits demonstrated no significant irritation after 10 d of exposure to the formulation.
Conclusion: The study demonstrated that in-situ gelling formulation of FCZ prepared using thermosensitive polymer had improved activity against Candida albicance and would be efficacious for the treatment of vaginal Candidiasis.
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