Continuous Slug-flow Crystallization Of N-acetyl-L-glutamine

Slug flow crystallization is a novel crystallization method,in which inert gas is introduced into the pipeline,crystallization solution in the pipeline is spontaneously generated alternative slugs of slurry and gas.The slug flow increases the surface area and mass heat transfer between liquid and gas when it introduced into the crystallization,which promotes the solution mixing,improves the process repeatability and eases for scale-up.N-acetyl-L-glutamine is one of the medicinal amino acids,which can be used in the treatment of brain injury coma,hepatic coma,high paraplegia and nervous diseases,it has good application prospect in medicine industry.Therefore,N-acetyl-L-glutamine has been studied in this paper due to its representative of the pharmaceutical amino acids.Its thermodynamic properties,crystallization kinetics,and the slug flow crystallization process in the continuous tube have been investigated in details.The specific contents are listed as follows:The solubility data of N-acetyl-L-glutamine in aqueous solution with different proportions of methanol or ethanol were determined with a static analytical method.The data were then correlated by five models including the modified Apelblat equation,Van't Hoff equation,local composition model(NRTL model),CNIBS/Redlich-Kister model,and Jouyban-Acree model.The results show that Van't Hoff equation agrees well with the experimental data.Besides,the melting temperature and fusion enthalpy of N-acetyl-L-Glutamine were measured by the differential scanning calorimetry and the thermodynamic properties including enthalpy,entropy and Gibbs free energy during dissolution were calculated accordingly.The metastable zone of N-acetyl-L-glutamine in water was measured by laser method,which provide a theoretical basis for the study of slug flow crystallization process.The cooling crystallization kinetics of N-AGM in water was experimentally measured by the batch dynamic method.The growth model of ASL was chosen according to the particle size distribution of crystals.On the basis of population balance equations,the moment transform method were chosen to calculate and correlate the experimental data by least squares method,and the model equations of the nucleation rate and the crystal growth rate in the crystallization process of N-AGM were finally obtained.The effects of supersaturation,suspension density,mixing rates and cooling rates on the nucleation rate and the crystal growth rate were investigated,respectively.Based on the results from thermodynamic and kinetic study,the slug flow crystallization process of N-acetyl-L-glutamine was studied.The effects of gas-liquid flow rate,solution supersaturation,residence time and pipe diameter on the crystal products were investigated in slug flow crystallization process.The appropriate parameters have obtained for the size-controlled and uniform size distribution N-acetyl-L-glutamine crystals in this work.