EVALUATION OF RECONSTITUTED HUMAN VAGINAL EPITHELIUM AS A MODEL FOR DRUG DELIVERY OF FLUCONAZOLE GEL FOR TREATING VULVOVAGINAL CANDIDIASIS.

Purpose: The goal of this project performed by researchers at the Massachusetts College of Pharmacy and Health Sciences was to evaluate the use of EpiVaginal, a reconstituted human vaginal epithelium, as a model for penetration for an antifungal gel containing fluconazole. A tissue culture based model for vaginal epithelium (EpiVaginal) has been developed by MatTek Corporation. The EpiVaginal culture model is a cell culture system made of normal, human ectocervico-vaginal (ECV) epithelial cells that were induced to form a three-dimensional tissue. Methods: The gel forming agents Carbopol 974NF, methylcellulose, and a combination of both Carbopol 971NF polymer and Noveoon AA1 USP polycarbophil were investigated because of their satisfactory profile for low irritation and toxicity. Gels with 1% fluconazole were formulated and the release of the drug from these formulations was compared using EpiVaginal tissue cultures. The skin permeation studies were conducted using tissue cultures. Hanks Buffer pH 7.4 was used as a receptor medium. 100 mg of test product is deposited onto the surface of the tissues. The cultures are incubated at 37°C for a specific time. A plot of the amount of fluconazole permeated, ug/cm2, versus time (hr) was used to calculate the flux. Results: Using a One Way ANOVA test (p< 0.05) the mean flux of the formula containing Carbopol 974 showed a significant difference as compared to the other two formulations. Conclusion: The use of EpiVaginal, a recently developed normal (non-cancerous), human cell-derived tissue, has been investigated in this study as a model for vaginal drug delivery.

Bioadhesive, Candida, Candidiasis, Carbopol gels, Drug delivery agent, Drug metabolism, EpiVaginal, Fluconazole, Franz diffusion cell, Gel formulations, Glycosaminoglycan, Hyaluronic acid (HA), Hylauronic acid, Metabolism, Methocel gels, Micro-adhesive, Permeability, Permeation , Three dimensional tissue, Vaginal, Vulvovaginal candidiasis

Carbopol 971, Carbopol 974, DI water, Fluconazole, Germaben, Glycerine, Hylauronic acid, Methoed K100, Novron AA1, Propylene glycol, TEA 99%