Study On Crystallization And Purification Of Cefuroxime Axetil

Cefuroxime axetil is a second-generation cephalosporin antibiotic that has good oral absorption.Cefuroxime axetil was clinically used in a variety of sensitive bacteria infections.At present,cefuroxime axetil produced in domestic has problems such as high impurityδ-3 isomer content,uneven particle size distribution,and product quality degradation caused by storage,which seriously affects the production,storage,and use of cefuroxime axetil.In this paper,the crystallization process and the degradation process of cefuroxime ester were studied based on the research background.The solubility of cefuroxime axetil in different solvents was determined by the laser dynamic method in the range from 278.15K to 313.15 K under atmospheric pressure.The experimentally determined solubility data were fitted by nonlinear regression using the Apelblat model and theλh model,which obtained the relevant model parameters.It provides basic data and theoretical support for the study of crystallization technology and crystallization kinetics.Study on the degradation kinetics of cefuroxime axetil solution.Using high-performance liquid chromatography（HPLC）and the single factor test was implemented to study the law of the content of cefuroxime axetil in the solution over time under different conditions such as the initial solution p H,temperature,and oxidant species.The chemical reaction kinetics method was used to establish the degradation reaction kinetics models of cefuroxime axetil under different conditions.The model parameters were obtained by regression and the half-life(t_1/2)was predicted.The degradation mechanism of cefuroxime axetil was analyzed from the molecular scale by Materials Studio simulation software.It provides data support for production process,crystallization process design,storage and application.The study on cefuroxime ester crystallization kinetics was carried out by utilizing intermittent dynamic method.The particle sizes of samples taken out at different time were measured by Mastersizer 3000 granulometer.Based on the Population Balance Equations,the experimental data was processed by using the method of Extrapolation and the Moment.Then the nucleation rate and growth rate models were obtained according to nonlinear regression method,and the influences of crystallization temperature,suspension density,supersaturation and stirring rate for crystallization process were analyzed and discussed.Finally,the calculation result of the Moment method with smaller error is selected as the dynamic model.The single factor test was implemented to systematically investigate the influence of process conditions such as the type and amount of eluent,stirring rate,temperature,and crystallization time on the crystallization process of cefuroxime axetil.With the purity,δ-3impurity content,δ-3 impurity removal rate,process yield,and particle size distribution of cefuroxime axetil crystal product being the research targets,the effect and control law of process operating parameters on the quality of cefuroxime axetil crystal product were analysised and identified.Crystal products with high purity,lowδ-3 impurity content and narrow size distribution were obtained in the laboratory.