The Study Of Disodium 5’-Ribonucleotide Anti-solvent Crystallization Based On Real-time Monitoring Platform

Disodium 5’-ribonucleotide(I+G)is an important food additive,which is composed of disodium 5’-inosine and disodium 5’-guanosine.A significant gap can be found in the quality of I+G products between the domestic and foreignal.Also the lack of advanced studies on thermodynamics and kinetics cause unclearity of I+G mixed crystallization process.In view of these problems,a crystallization process monitoring and control system(CPMCS)was developed in this work,and based on the CPMCS,on-line concentration measurement,thermodynamics and kinetics of I+G cooling/anti-solvent crystallization process were studied.First,CPMCS was developed based on LabVIEW,which integrated ATR-UV/vis spectroscopy,Raman spectroscopy and other technologies to achieve the critical process parameters data logging,analysis and process control.I+G aqueous ethanol mixtures,a binary solute and binary solvent system,was selected as model system.An on-line concentration monitoring method for the model system was established by using ATR-UV/vis spectroscopy,which coupled with a modeling method of partial least squares regression.After calibrating the effect of temperature and solvent composition,the prediction error of the method developed was within±10%,which meets the needs of practical applications.Then the solubility of the model system was on-line determined based on the method developed.The modified Apelblat equation and Jouyban-Acree model were used to correlate the solubility data,and the results showed reasonable accuracy with precision adj-R~2>0.92.On-line supersaturation monitoring was also carried out by combining on-line concentration measurement and solubility data,and the concentration profiles could be observed effectively during crystallization process.Second,coupling with FBRM,the kinetic parameters of anti-solvent/cooling crystallization were investigated.The exponential empirical function was selected to regress nucleation and growth kinetic equations.The kinetics data was well fitted with adj-R~2>0.7.The effects of different cooling rates and anti-solvent addition rates on the metastable zone widths(MSZW)were studied,and the opposite effect on MSZW was found.This work provides the basic thermodynamics and kinetics data of I+G aqueous ethanol system as well as on-line concentration measurement method,which would be helpful for developing,optimization and quality control of the I+G crystallization technique.