Process Optimization Of Cefotaxime Sodium

Since 1970s, the development of cephalosporins is the fastest, most listed varieties of antibiotics.The development of our country’s cephalosporins is in 1980s, with its rapid development momentum, it has reached a high level in the current. Cefotaxime sodium has broad spectrum antibacterial, good efficacy, low allergy and stable to p-lactamase, which has been well received by patients,In the process of Industrial production the dosage of the starting material of cefotaxime sodium is large, and the batch is much more. A quick and accurate identification method is needed to realize the quick screening of the raw material. The synthesis of cefotaxime sodium has two main steps. Cefotaxime acid is obtained by reaction of 7-ACA and MEAM in accelerant, then, reacting with salt forming agent generates cefotaxime sodium, and the good quality products are obtained by crystallization finally. In existing process the yield of the first step reaction is about 91.5%, and the yield of the second step reactiong is about 92%.In this experiment, a fast and nondestructive near infrared spectroscopy analysis technique is used, established the identification model of MEAM,7-ACT and ceftriaxone sodium. Model identification rate and rejection rate are 100%, and the quality of cefotaxime sodium is controlled by the source.Secondly, the method of single factor experiment and orthogonal experiment is adopted in the expetiment. The effect of the ratio of triethylamine and 7-ACA, reation time, and reaction temperature on the yield in the first step of the synthesis of cefotaxime sodium was explored, and the yield was also investigated with different solvent conditions. The optimal production conditions were determined:the ratio of triethylamine and 7-ACA is 2:1, reaction time 60 min, and temperature 5℃. Determind the optimal solvent for dichloromethane-ethanol system. Under the optimal preparation process, the yield is 98.2%.Finally, A combination of single factor experiment and orthogonal experiment was used to expore the effect of reaction temperature, amout of isopropanol and varieties of salt forming agents of the synthesis of cefotaxime sodium, and investigated the effect of crystal type and product yield under different seed crystal. The optimal production conditions were determined:temperature 15℃, amout of isopropanol is 100mL, sodium 2-ethylhexanoate as the salt forming agent and choosing rodlike seeds. Under the optimal preparation process, the yield is 96.2%.