Reactive Crystallization Of 7-ACA

7-amino-cephalsporanic acid is an important intermediate in the manufacture of semisynthetic cephalosporanic antibiotics. With the increasing level of the people's living and taking medicine, the demand for cephalosporins manufactured by 7-ACA increased correspondingly. Therefore, 7-ACA plays an important role in medical field. But there are many problems in manufacturing 7-ACA. Crystallization process is the critical step of determining the quality of production, so the semi-batch reactive crystallization of 7-ACA was studied systematically both in experiment and theory.First, the crystallization thermodynamic data and other basic physicochemical data of solution ,such as viscosity ,density of 7-ACA solution and dissociation constants, were measured by experiments.Using gravimetric method, the solubility of 7-ACA under different pH was measured. As a kind of zwitter, the solubility of 7-ACA changes largely with the change of pH. Using the experiential equation to calculate the above solubility , the result tallies with the experimental data. 7-ACA exists in solution as three forms: anions, cations and neutral dipolar species, and there is a minimum at the isoelectric point. When pH is lower or higher than isoelectric point, the solution of 7-ACA increases dramatically and anions and cations are predominant in the solution. The activity coefficients of the lower and higher pH were obtained using regression. The supersaturation of 7-ACA was gained by laser method, and the acid metastable width was obtained through these data. The above information are useful in designing and controlling of crystallization process. Estimation of kinetics parameters is essential important in designing industrial crystallization process. Crystal acid kinetics of 7-ACA was measured by batch dynamic method, and used diiscietized population balance model to regress experimental results. The kinetic model of nucleation, crystal growth and agglomeration were established. The induction period was measured by eyeballing method and the relationship between induction period and supersatuation was gained. Using the induction period data, the solid-liquid interfacial tension and crystal nucleation index were estimated.Through experimental research, dissolution, decoloration, adding rate of acid and alkali, temperature, speeding rate, adding seed, filtration and desiccation of 7-ACA crystal process were optimized. By indexing the 7-ACA powder X-ray diffraction data, we obtained cell parameters.