Mucoadhesive vaginal film of fluconazole using cross-linked chitosan and pectin

Abstract

Mucoadhesive vaginal film of fluconazole was formulated for improving contact with vaginal mucosa and convenience in treatment of vaginal candidiasis using chitosan and pectin as a cross-linking polymer. The films were evaluated for thickness, elongation, tensile strength, drug diffusion, moisture content, swelling study, drug content, folding endurance, in vitro diffusion study, ex vivo diffusion study, in vitro antifungal activity, in vivo irritation study. Preliminary trials were carried out for selection of polymer, permeation enhancer and plasticizer. Films were prepared using chitosan:pectin (75:25) with glycerol as plasticizer. Dimethyl sulphoxide (DMSO) was selected as permeation enhancer amongst various permeation enhancers due to its highest drug diffusion. To evaluate role of plasticizer and permeation enhancer in optimization, 32 full factorial design was used. Diffusion was found to increase as concentration of DMSO increased. Optimized batch showed 79% drug diffusion in 24 h, 8.7 N mm−2 tensile strength, 10% elongation, 2.5 moisture content and 2.2 swelling index. In vitro antifungal activity was carried out using Candida albicans and non-interference on Lactobacillus action. Differential scanning calorimetry and X-ray diffraction study confirmed cross-linking of polymers. In vivo vaginal irritation study indicated no signs of erythema and inflammation at vaginal site of healthy female rabbits at the end of 3 days.