Online Concentration Measurement And Process Improvement Of I+G Crystallization

Disodium 5’-ribonucleotide(I+G) is composed of two kinds of nucleotide, disodium 5’-inosinat(IMP) and disodium 5’-guanylate(GMP), which is widely used in industries of foods and pharmaceuticals. While, compared with foreign similar products, there are visible qualitative shortages in purity, morphology and crystal size distribution of domestic I+G crystal products. Crystallization process is the key point in quality control for I+G products, and supersaturation is the basic factor of crystallization process control. In this paper, on-line concentration measurement of I+G in water + ethanol solvent mixtures was established and applied to different crystallization process.This study mainly includes:(1) a novel approach is presented to correlate on-line concentration of IMP and GMP in IMP+ GMP+ water + ethanol solution with the attenuated total reflection/ultraviolet(ATR-UV) spectrum by using bivariate calibration method, the selected wavelengths are 250 nm and 274 nm by using Kaiser method. The method was developed under the fully consideration of concentration, temperature, anti-solvent and particle effect on ATR-UV spectroscopy. Also the limit of quantitation(LOD) and the limit of detection(LOQ) were determined, and the correlated concentrations are well consistent with the measurement of HPLC method.(2) Solubilities of IMP and GMP in water + ethanol solvent mixtures were measured by ATR-UV on-line concentration measurement. And the obtained model was used to detect I+G concentrations in the anti-solvent cooling crystallization.(3) On the basis of comparing various crystallization process, the vacuum evaporation with anti-solvent and cooling crystallization equipment was used for I+G production, where the influence of evaporation volume, evaporation time and other processing parameters on the particle size distribution and crystalline form of I+G producte were investigated and discussed in detail.This work would provide essential data and thoughts of process improvement for I+G crystallization.