The Study Of Microemulsion For Dermal Delivery Of Penciclovir

Penciclovir is a potent antiviralguanosine-type drug which maintains the antiviral activity against Herpes Symmplex Virus, Varicella Zoster Virus, Epstein-Barr Virus, Hepatitis Virus and Cytomegalovirus. However, it has a poor bioavailability of 5%～10% after oral administration, and a poor ability of permeation, the clinical use of penciclovir is limited.There are several advantages of microemulsion for the dermal delivery of drugs. First, the concentration of the skin is increased due to large amount of drug can be incorporated in the formulation. Second, the increased thermodynamic activity of the drug may favor its partitioning into the skin. Third, the ingredients of microemulsion may reduce the diffusional barrier of the stratum corneum and increase the permeation rate of drug via skin by acting as permeation enhancers. In order to promote the ability of permeation for penciclovir into skin, penciclovir microemulsion was prepared and its physico-chemical property, the ability of permeation in vitro and in vivo were evaluated.The basic components of the formulation were determined by investigating the saturated solubility of penciclovir in various medium and the interaction between oils, surfactants, and cosurfactants. The pseudoternary phase diagrams of microemulsion (ME) were drawn to determine the MEs area. A simplex lattice experiment design was applied to optimize the composition of microemulsions. The concentration of surfactant, cosurfactant and water were selected as independent variables, and the solubility and the cumulative amount of penciclovir permeated through excised mice skins per unit area(Qn) at 12 hours were selected as the response variables to optimize the ME formulation and the final formulation (containing oil (oleic acid) 5%, surfactant(Cremorphor EL) 20%, cosurfactant(ethanol) 30%, water 45%) had been found.The MEs presented as small spherical drops under electron microscopy, with the average diameter of 36.5nm. Its basic character parameters such as viscosity, refraction, electric conductivity, pH were 7.11±0.12mm²Â·s^-1, 1.38±0.0005, 134.5±1.56－μs·cm^-1, 5.33±0.09, respectively. The test of influencing factors and primary stability indicated that the penciclovir ME has a good stability at room temperature and no-light conditions.In vitro the Qn of PCV of MEs at 12 hours was transdermal delivery kinetics were studied after applied 0.5%(w/w)PCV-ME, 0.5%(w/w)PCV-ME gel and l%(w/w)futan cream using the mice skin in vitro. The results show that the permeation rate was obviously higher following ME preparations application compared with that following the cream application(p<0.05).In vivo the PCV concentrations in the epidermis and the dermis were investigated after applied 0.5%(w/w)PCV-ME, 0.5%(w/w)PCV-ME gel and l%(w/w)futan cream. The concentrations were obviously higher both in the epidermis and in the dermis following ME preparations application compared with that following the cream application(p<0.05). The ME preparations also show an ability of delayed-release.The irritancy test indicated that PCV-ME and PCV-ME gel is safe for transdermal drug delivery after once or more times application,the integrity of skin could be guaranteed.