Studies on bioadhesive controlled release vaginal dosage forms

The aim of this study is to develop the controlled release, bioadhesive vaginal system of two different drugs which are used for systemic or topical effect and to measure their effectiveness.Cidofovir and oxybutynin hydrochloride are selected for local and systemic effect, respectively. Various new formulations for vaginal administration, such as bioadhesive gels, liposomal gels and microsphere-gels were developed.Hydroxpropylmethycellulose (HPMC), chitosan, Carbopol, poloxamer and their mixtures were used for the preparation of the vaginal dosage forms.The required properties of active ingredients and polymers were determined. Some properties of the gel formulations such as appearance, pH, viscosity, flow, diffusion (in Franz Diffusion cell) and mucoadhesion were investigated. Since oxybutynin is a systemically effective drug, the diffusion experiments of the gel formulations containing oxybutinin through the rabbit vaginal tissue were also carried out using horizontal diffusion cell.The vaginal gel formulation of cidofovir CV-HPMCK100M2 formulation prepared with HPMC showing optimum controlled release and mucoadhesive properties based on the in vitro studies of the cidofovir formulations developed. The effectiveness of this final formulation was tested with cell culture studies and it was found to be effective.The effectiveness of oxybutynin vaginal formulations of OXB-HPMCK100M2 (with HPMC), OXB-KITH3 (with chitosan) and OXB solution were compared with the oral tablet formulation in rabbits. Sustained plasma profile was obtained with OXB-HPMCK100M2 formulation. The relative bioavailability was found to be 179 %. However damage on vaginal epitel cells was observed in this group; based on histological studies. No damage was observed in OXB-KITH3 group.Keywords: Oxybutynin, Cidofovir, urinary incontinence, HPV, HSV, genital warts, bioadhesive vaginal dosage forms, gel, microsphere, liposome