基于MSMPR体系的头孢丙烯连续结晶综合实验设计  

Comprehensive experimental design of continuous crystallization of cefprozil in MSMPR system

作　　者：程晓伟 任静 杨月怡 陈正威 舒俊宁 刘宝树[1] 孙华[1] CHENG Xiaowei;REN Jing;YANG Yueyi;CHEN Zhengwei;SHU Junning;LIU Baoshu;SUN Hua(School of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China;School of Chemistry and Chemical Engineering,Hainan University,Haikou 570228,China)

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]海南大学化学化工学院,海南海口570228

出　　处：《实验技术与管理》2024年第12期76-84,共9页Experimental Technology and Management

基　　金：国家自然科学基金项目(22208075);海南省自然科学基金项目(522QN276);河北省高等学校省级线下一流课程建设“化工原理”(冀教高函[2020]25号);河北省高等教育教学改革研究与实践项目(2022GJJG192);河北科技大学一流线下课程建设“化工原理实验”(120087640)。

摘　　要：该文设计了头孢丙烯在二级MSMPR体系中的稳态连续结晶实验。基于粒数衡算方程,确定了头孢丙烯二级MSMPR连续结晶动力学,构建了该体系的成核速率和生长速率模型,并验证了模型预测的准确性。进一步考察了不同过程影响因素对头孢丙烯连续结晶过程的影响,明确了较佳的连续结晶工艺,且该工艺制得的产品质量实现了较大提升。该实验有利于培养学生的工程实践能力,引导他们将专业理论知识与科学前沿相联系,有利于激发他们的求知欲和探索欲。[Objective]Crystallization is a significant operational unit that is widely used in the separation,purification,and preparation processes of solid materials,which generates solid materials with desirable properties,including shape,particle size distribution,and purity.Continuous crystallization has drawn increasingly more attention due to the even temporal and spatial distribution of the concentration and temperature,which can produce stable and high-quality products.To meet the requirements of chemical engineering and pharmacy professionals who are under training for experimental teaching of crystallization,as well as deepen the understanding of continuous process,and develop data processing and analysis skills,steady-state continuous crystallization experiments on cefprozil in a two-stage mixed-suspension mixed-product removal(MSMPR)system were designed.[Methods]The continuous crystallization experiments on cefprozil in the two-stage MSMPR system were performed at the isoelectric point.The suspension density was determined by the slurry sample weight loss before and after drying,and the solution concentration was obtained by the solvent loss on drying.The particle number density was obtained on the basis of the particle size distribution using a Malvern Mastersizer 3000 particle size analyzer.The continuous crystallization kinetics of cefprozil in the two-stage MSMPR system was further determined based on the population balance equation.The growth and nucleation rate models were respectively regressed depending on the data at the various operation parameters.The effects of the primary concentration,pH,crystallization temperature,and stirring rate on the crystal quality,including the mean particle size,yield,diameter span,and particle size distribution,were respectively investigated.[Results]The results indicate that,as the temperature increases,the growth rate shows an increasing trend,while decreasing temperature and increasing stirring rate promote the process of crystal nucleation.Based on the suspension den

关 键 词：连续结晶 头孢丙烯 粒数衡算方程 结晶动力学 MSMPR 

分 类 号：TQ46[化学工程—制药化工]