Research On The Reaction And Crystallization Process Of Cefuroxime Sodium

Cefuroxime sodium, the national essential drug, is a kind of cephalosporins. This drug is widely used in chemical and pharmaceutical industry. To present, the domestic cefuroxime sodium products commonly have the problems of high color grade, low purity, serious coalescence, poor crystal habit and poor stability. In this paper, aiming at solving these existing problems, the crystallization process of cefuroxime sodium was studied systematically and deeply. A new crystallization method of cefuroxime sodium was developed.Firstly, the thermodynamic properties of cefuroxime were studied. The dynamic method was used to measure the solubility of cefuroxime acid in mixed solvent systems(water + ethanol, solvent A + acetone, water + solvent A), the solubility of cefuroxime sodium(form ?) in mixed solvent systems(water + solvent A, water + solvent A + ethanol, water + solvent A + 1-propanol, water + solvent A + solvent B) and the solubility of cefuroxime sodium(form ?) in pure solvents(water, solvent A). What's more, the simplified Apelblat equation, the(CNIBS)/Redlich-Kister equation, the Jouyban-Acree equation and the van't Hoff equation were used to fit the experimental data. The relevant thermodynamic properties were also calculated in this paper. These studies provided basic data for the design and optimization of the crystallization process.Secondly, the degradation kinetics of cefuroxime sodium in solvents was studied in this paper. The high performance liquid chromatography(HPLC) analysis method was used to measure the degradation kinetics data of cefuroxime sodium. The degradation reaction orders of cefuroxime sodium in mixed solvent system(water/ solvent A = 0.43) and in water were determined, and the degradation rates in this two solvent systems were compared. Then the effects of initial concentration, temperature and the value of pH on the degradation of cefuroxime sodium in water + solvent A system were studied systematically. These studies provided theoretical basis for the optimization of the crystallization process.Lastly, the reaction and crystallization process of cefuroxime sodium was designed and optimized, including choosing solvent system, determining the crystallization method, optimizing the parameters of temperature, salt forming agent, pH, stirring rate and anti-solvent. The optimized operating conditions of the new crystallization method were finally determined.The cefuroxime sodium products with low color grade, high yield, high crystallinity, good shape and high stability were produced by the new method developed in this paper.The above researches have not been reported in any literatures.