Comprehensive experimental design of continuous crystallization of cefprozil in MSMPR system
[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 density and relative concentration at different temperatures and stirring rates,the nucleation and growth rate models of this system were also constructed.The fitting values of different parameters in the models indicate that nucleation and growth rates show a positive relationship with relative concentration,stirring rate,temperature,and suspension density.Moreover,the nucleation rate is mainly dependent on the relative concentration,as the fitted parameter of relative concentration is the largest among the studied parameters.In addition,the dependency of the growth rate on the relative concentration is stronger than that of the nucleation rate,as the fitted parameter of relative concentration in the growth rate model is larger than that in the nucleation rate model.Furthermore,the accuracy of the model prediction was further validated.The calculated values for the crystal nucleation rate and growth rate models show good agreement with the corresponding experimental values.The results suggest that the crystal nucleation rate and crystal growth rate models show better predictability.Then,the influences of various factors,including the primary concentration,pH,crystallization temperature,and stirring rate,on the continuous crystallization processes were further investigated,and the optimal continuous crystallization process was determined,leading to better improvement in the quality of the products produced by this process.[Conclusions]This experiment can help students develop the ability to engineering practice,guide them to associate professional theoretical knowledge with hot topics of scientific research,and stimulate their desire for knowledge and exploration.
万方数据
维普
