Research Of Hot Melt Extrusion Technology In Preparation Of Solid Dispersion Of Phenoxyacetate Acid Pyrazine Esters Compounds FC

FC was phenoxyacetate acid pyrazine esters compounds which synthetics by ligustrazine and fenofibrate acid.It could also have hypolipidemic effectave and decrease the viscosity of the blood.It Belongs to the category of innovative medicine which is not listed.This research was to use hot-melt extrusion technology to produce the poorly water-soluble drugs which was the solid dispersions of FC.It mainly investigated the technology in the preparation of solid dispersions,to improve the dissolution of the poorly water-soluble drugs and the role of the solid dispersions when contained the solid dispersions of FC in animals.First of all,refer to the relevant references,and the 1.0%SDS solution was selected as the dissolution medium which throughed the determination of equilibrium solubility.We established the ?Ltraviolet analytical method for the determination of FC in vitro release.The methods after the methodology validation method were accurate,fast and convenient.In addition,high performance liquid chromatography(HPLC)was established for determination of the related substances.Through the potential method for the of determination of the content.Using group contribution to calculate the solubility parameters of FC is 22.82 MPa1/2.We had calculated the solubility parameters of some common carriers,and chosen PEG6000,PVPK30,Poloxamer188 as the carriers with the good compatibility.They were used to the hot-melt extrusion for the next step.This study was focus on using hot-melt extrusion to produce the different solid dispersions.Firstly,we studied the dissolution when the proportion of drug and carrier was 1:4.The results showed that the dissolution of the solid dispersion was obviously better than the physical mixture.Then compared the dissolution of the drug with three different carriers in different drug loadings and different temperature.DSC and X-ray diffraction analysis was carried out on the identification of the dispersion,We studied the existence state of drugs in different carriers.Then we examined the stability of Poloxamer188 and PVPK30 soliddispersion.we chose content,appearance,dissolution as the index of stability evaluation.In addition,we also investigated the properties of the solid dispersions in different storage conditions(room temperature 40 ?,and RH75 %)and different lofting time.We found that was better using PVPK30 as the carrier.We chose FC-PVPK30(1:4)which had better stability as the further processing,Using microcrystalline cellulose as the filling agent,crosslinking carboxymethyl cellulose sodium and 20% magnesium stearate as disintegrating agent and lubricant.Finally we established the method in SD rats with HPLC,the methods after the methodology validation method were accurate,fast and convenient.Giving th drugs to the animals from the stomach,then we measured the concentrations of drug after the adminstration.We analyzed with the data by DAS version 2.0 statistics software.We found the peak concentrations(1.612 ± 0.152)mg/L was(2.333 ± 0.517)h in the matched control group,the peak concentrations(1.628±0.171)mg/L was(2±0)h in the experimented group.The bioavailability of the experimented group was 103.37±63.31% which wasn't significantly improve,and analysed the reason.