Preparation And Evaluation On Pentoxifylline Gel

Pentoxifylline(PTX), which would improve the blood circulation of the brain and the limbs and increase the volume of blood flow in arteries and capillaries, was used for the cure for the disease of peripheral vessels such as thromboangiitis obliterans(TAO) as a common drug. It was generally used by oral administration or intravenous injection. However, the manifest first-pass effect results in a low bioavailability and the half time is short. Furthermore, oral administration and intravenous injection will cause adverse effect to some extent. So, PTX is more suitable for external use for topical disease.Firstly, some physicochemical properties were determined. Such as equilibrium solubility, octanol/water partition coefficient and the effect of pH value on it, and the methods of UV Spectrum Photometry and High Performance Liquid Chromatography (HPLC) were established. In this thesis, the traps-dermal delivery across mouse skin of PTX gels was studied by using diffusion cell. The formulation was optimized with the indexes of the physical character and the accumulative permeated quantity. The contents of the basic formulation are as follows: Cambopol-934(0.25%) was chosen as the base; the content of drug is 2%; and glycerin(25%)was taken as the humectant. Furthermore, the effect of several kinds of permeation enchancers was studied. Among the enhancers chosen, 3%azone+5% propylene glycol showed the best enhancement effect.The drug concentration in topical tissue after oral and topical application at different times was measured by microdialysis in vivo. During the time of experiment, the concentration of tissue after topical application was higher than that after oral application. Therefore, it was showed that the preparation was availability on the topical disease.The drug concentration of plasma after oral and topical application was also determined. The concentration of plasma after topical application was lower than that after oral application. According to that, it was showed that the preparation was security on the systemica circulation.The result of the irritancy experiment proved that the gels had no irritancy to skin, so it could be considered as a safe vehicle for topical drug delivery systems. And the result of the pharmacodynamics experiment showed the gel could decrease the lesion severity of affected limb.