Preparation And Evaluation On Flurbiprofen Liposome Gel

Flurbiprofen (FP) is a new nonsteroidal anti-inflammatory drug (NSAID) which is widely used in the treatments of rheumatic arthritis, rheumatoid arthritis, osteoarthritis and traumatic pain in clinics. However, like other NSAIDs, it may bring adverse effects (e.g. gastralgia nausea and diarrhoea) on gastrointestinal tract when orally administrated. Even bleeding and ulceration often occur. Therefore, liposome was selected to carry FP into local deeper tissues and avoid high plasma concentration. It is important to minimize the side effects of oral FP and increase curative effect. Taking into the consideration of poor stability of liposome and the inconvenience of liquid administration, FP liposome gel was finally prepared.UV spectrophotometry was used for the investigation of the pharmaceutical preformulation of FP. The ionization constant was determined as 5.42. The solubility and oil/water partition coefficient of FP were correlated with the pH value of aqueous media. With the increasing value of pH, the solubility of FP increased, while the oil/water partition coefficient decreased.FP liposomes were prepared by Ethanol Injection method. The optimized formulation of FP liposomes was 0.5% FP+4% PC+0.5% CHOL+0.04% V_E+PBS7.4(17mM) which optimized by orthogonal design.The Minicolumn Centrifugation method and Dialysis method were used to separate the free FP from liposomes, and the concentration of FP in liposomes was determined by HPLC method. The entrapment efficiency(EE) of FP liposomes with mean particle size of 181.8 nm were 46.7%and 41.6% for Minicolumn Centrifugation method and Dialysis method respectively.The transdermal delivery of FP liposomes across rat skin was studied by modified Franz diffusion cells in vitro. The results showed that comparing to larger ones, liposomes with small particle size enhanced permeation of FP into the skin. When donor compartment was under nonocclusive situations, the cumulative amount was higher than that of occlusive ones. The bilayer structure of liposomes was necessary to promote the permeation of FP. Pre-treating the rat skin with 3% azone could increase the cumulative amount of FP, on the contrary, the increasing amount of cholesterol would decrease it. The charge of FP liposomes had no effect on the permeation of FP.On the basis of the studies mentioned above and the some reported literatures, carpobol was...