Study On The Reaction And Antisolvent Crystallization Process Of Cefoxitin Sodium

Cefoxitin sodium is the second generation of cephalosporins antibiotics.It is widely used in chemical and pharmaceutical industry.To present,the domestic cefoxitin sodium products generally exist the problems of poor crystal habit,serious coalescence,difficult dry,low crystallinity,poor stability and other issues.Aiming at solving the existing problems of cefoxitin sodium,the reaction process and crystallization process of cefoxitin sodium were systematically studied.A new crystallization method of cefoxitin sodium was developed.The thermodynamics properties of cefoxitin were studied.Cefoxitin acid is the raw material for preparation of cefoxitin sodium.Thus its quality and dissolving properties may have important influence on the quallity of the product.In this research,cefoxitin acid was recrystallized to prepare two different polymorphs with high purity of cefoxitin acid-anhydride and monohydrate.The structures and mophologies of different polymorphs of cefoxitin acid were characterized and analyzed.The solubility of cefoxitin acid in methanol,ethanol,n-propanol,isopropanol,ethyl acetate,acetonitrile,methanol-water solvent system and the solubility of cefoxitin sodium in methanol,ethanol and n-propanol was measured by UV spectrophotometry.The solubility data were fitted by Apelblat simplified equation,NRTL equation,CNIBS / Redlich-Kister equation,and the dissolution enthalpy of cefoxitin acid in the solvent was calculated.The degradation kinetics of cefoxitin sodium in solvent A-solvent B system was studied.The high performance liquid chromatography(HPLC)was used to measure the degradation kinetics data of cefoxitin sodium.The effects of solvent composition,initial concentration,temperature,water on the degradation of cefoxitin sodium in solution were studied systematically.These studies will provide theoretical basis for the optimization of the crystallization process.The reaction and crystallization process of cefoxitin sodium were designed and optimized,including the selection of solvent system,the selection and optimizing of the ratio of solvent,temperature,salt agent,anti-solvent,stirring rate and raw material.The cefoxitin sodium products with good shape,high stability,easy drying,high yield and high crystallinity were produced by the new method in this papar.The above researches have not been reported in any literatures.