Study On The Process Of Dilution Crystallization Of 5'-GMPNa₂

Disodium 5'-guanylate heptahydrate (5'-GMPNa2) is an important food additive and medicine material, which belongs to the second-generation fresh reagents. 5'-GMPNa2 exists in two solid forms: amorphism and crystal. In order to overcome the fault of 5'-GMPNa2 product quality, such as amorphic state, lower purity and inconstant water content, a systematical study on the crystallization process of 5'-GMPNa2 had been presented in this thesis. A new crystallization process has been developed, with which the high quality crystals of 5'-GMPNa2 (formⅠ) can be obtained. The main contents in this thesis go as follows.The polymorphic transition process of 5'-GMPNa2 from amorphism to crystal (formⅠ) was investigated by in-situ monitoring technique( FBRM and PVM) and ex-situ monitoring technique(powder-XRD). The transition mechanism was deduced to be solution mediated transition (SMT). The effects of pH, additive, solvent ratio, temperature and particle size of raw materials on transition rate and transition degree were studied.By the use of X-ray single crystal diffraction technique, the crystal structure of 5'-GMPNa2 was determined. In addition, the powder X-ray diffraction pattern of 5'-GMPNa2 from dilution crystallization was measured. By comparing the single crystal diffraction data and the powder-XRD pattern, it can be concluded that the dilution crystallization product is form I of 5'-GMPNa2. With commercial software Cerius2, the crystal morphology in the vacuum was calculated based on BFDH and AE principles. The factors that may affect the crystal habit were discussed.The non-isothermal dehydration behavior of 5'-GMPNa2 was investigated by thermogravimetry /differential thermal analysis (TG-DTA). The dehydration kinetics were achieved from the TG-DTA curves by both the differential method and the integral method. The dynamic dehydration processes for all four steps are best expressed by the Z-L-T equation, suggesting a three-dimensional diffusion-controlled mechanism. The dehydration kinetics parameters, E and A, were calculated.The solubilities of 5'-GMPNa2 at different temperature and solvents were measured with dynamic method, and correlated by empirical equation,λh equation and CNIBS/Redlich-Kister equation, respectively. The dependence of solubility on pH and additive were studied, and results were correlated by the principle of ionization equilibrium and polynomial model respectively. The metastable zone and induction period for crystallization of 5'-GMPNa2 were also measured. The solid-liquid surface tension was estimated from primary nucleation theory.The dilution crystallization kinetic behaviors of 5'-GMPNa2 were measured with batch dynamic method. By moment transformation method, and basing on particle size independent growth– particle size independent multi equal volume breakage model, the population balance equation was solved. By non-linear least square method, the mathematical models for crystal growth rate, secondary nucleation rate, breakage rate constant and daughter distribution were established.On the basis of population balance equations and crystallization thermodynamics, kinetics, as well as mass balance equations, the mathematical model for dilution crystallization process of 5'-GMPNa2 was established. The effects of operation conditions on the crystallization process and the quality of product were studied in detail by both experiments and model simulation, on the basis of which the optimal operation strategy was established. And the high quality crystals of 5'-GMPNa2 (formⅠ) were obtained.No same report to above study results has been published in literature up to date.