Preparation And Pharmacokinetics Of Diclofenac Sodium (DS) Multiple Unit Sustained Release Pellet-Tablets

The purpose of this study was to develop a method to prepare Diclofenac sodium(DS)sustained release pellets and compress them into pellet-containing tablets without losing sustained release property.The diclofenac sodium sustained-release pellets were prepared by extrusion-spheronization,fluidized bed coating and pellet compression technique.And the release behavior in vitro and the pharmacokinetic behavior of the drug were discussed.The establishment of accurate and scientific research and testing methods,is to carry out the project prescription process must do before the work.Therefore,this paper refer to Chinese pharmacopoeia 2015 version of the ultraviolet spectrophotometry is established for detecting preparation s in vitro dissolution behavior.The Study used purified water as dissolution media(50r/min),collected right amount of dissolution liquid respectively in 0.5 h,1 h,1.5 h,2 h,3 h,4 h,5 h,6 h,8 h,measured 5 ml successive filtrate,then diluted with purified water to volume in 10 ml volumetric flask.Finally we detected samples under 276 nm wavelength.and detection wavelength of 276 nm,sample quantity 10 uL test preparation content.The establishment of a sensitive,reliable high performance liquid chromatography was used to detect the content of preparation and the concentration of plasma in vivo.And the mobile phase was mixing methanol with 4% glacial acetic acid solution at 70:30.The detection wavelength was 276 nm and the injection volume was 10 uL.The results showed that it could blend microcrystalline cellulose 101,lactose monohydrate and diclofenac sodium together at 3:5:2,then added 96 g HPMCE15 solution(0.2%)to the blend.Final the diclofenac sodium pellets with particle size of 0.45 mm were prepared by extrusion-spheronization.When the ratio of talc and coating material was 1:1,the coating operation could be conducted successfully without pellet conglutination and the coating weight gain was 27%,the dissolution of the coating pellet was desired by pellets aging 24 hours immediately.It could produce a constant drug release rate by blending SR-coated pellets of 27% weight gain with material at the ratio of 4:6,adding appropriate amount of polyvinyl pyrrolidone(PVP)K30 aqueous solution,granulation,drying and tabletting.The pellet-tablets obtained in this technique were similar to non-compressed sustained-release pellets through dissolution and SEM in vitro.The release behavior of diclofenac sodium multi-unit sustained-release pellettablet and self-made diclofenac sodium tablets in rabbits was investigated by single-dose dosing experiment.The pharmacokinetics of diclofenac sodium in plasma was evaluated by high performance liquid chromatography(HPLC).The peak concentration Cmax of oral sustained-release pellet-tablet was 44.5727 ug/L,peak time was 3 h,the half-life was 4.0319 h,and the peak value Cmax of oral tablet was 62.1141 ug/L,the peak time was 2.5 h and the half-life was 2.0108 h.The peak value of diclofenac sodium and diclofenac sodium sustained-release pellet-tablet in the rabbit can visually show that achieve significant sustained release effect,avoid the drug in the body of the burst effect,show a good sustained release effect in vivo.