| Fluconazole is an antifungal drug that exhibits fungistatic and fungicidal properties depending on the concentration. Fluconazole has been shown to be an effective antifungal agent, appropriate for vulvovaginal candidiasis, oropharyngeal and esophageal candidiasis, cryptococci meningitis and onychomycosis. The recommended dosage of fluconazole for vaginal candidiasis is 150 mg Diflucan tablet, as a single oral dose. The recommended dosage of fluconazole for oropharyngeal and esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily.;Diflucan causes high rates of side effects, with nearly 1 in 7 reporting reactions such as severe rashes, itching, skin inflammation, nausea and abdominal pain, dizziness, jaundice, and liver problems. In particular, Diflucan is noted for elevating liver enzymes. In more severe and rare cases, it can instigate cholestasis, hepatitis, and even hepatic failure in already weakened patients.;An attempt was made to evaluate the feasibility of developing vaginal formulation of this drug, as a means to overcome its side effects when administered as an oral dosage.;Various vaginal formulations of fluconazole were formulated using bases like HPMC gel, non-ionic and cationic base cream with an optimum pH and further evaluated for in vitro drug release characteristics using cellulose membrane and human cadaver skin. The hierarchy of drug release was observed as follows: cationic emulsion cream > HPMC gel system > non-ionic based cream. Further the effects of various penetration enhancers like propylene glycol, polyethylene glycol 400 and DMSO (dimethyl sulphoxide) at a concentration of 5%, 10% and 15 % on drug release were evaluated. It was found that, the addition of propylene glycol at a concentration of 15% gave better drug release from the cationic emulsion base containing 1% fluconazole. Furthermore, these formulations were studies over an extended period of 12 hours, it gave 28.5% drug release from cationic cream base in comparison to the release from the HPMC gel base and non-ionic cream base which is 26.5% and 22.0% respectively.;Human cadaver skin was then used as a barrier to assess the drug release from the formulation. As expected the drug release from both the formulations tested were significantly reduced due to resistance posed by skin. After 12 hours the drug release from cationic cream base with propylene glycol was 15.5 % and with the control was 14.0%. Once again this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their antifungal effects using yeast. The results correlated to the in-vitro drug release profile, where the cationic cream base with propylene glycol exhibited a zone of inhibition thereby indicating antifungal activity. The release data was treated to determine the physical parameters that influence drug diffusion, and the values for the diffusion coefficient were found to be highest with cationic emulsion cream based formulation containing 1% fluconazole with 15% propylene glycol. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect. |
