Study On Crystallization Process Of Pyridoxal Ceftazidime

As the third generation of cep Halosporin antibiotics,ceftazidime has strong antibacterial action against gram-negative bacilli,which is significantly higher than the first and second generation cep Halosporins.Ceftazidime is mainly applicable to respiratory infections,such as pneumonia,bronchitis,lung abscess,pulmonary cystic fibrosis,infectious bronchiectasis and so on.Ceftazidime can also be used to treat pulmonary infection of pseudomonas in patients with cystic fibrosis.At present,the production of ceftazidime is mainly intermittent operation,which has some shortcomings such as high energy consumption,high cost and poor product quality.In this study,a kind of ceftazidime crystallization process was developed and its crystallization process was studied systematically.The solubility and supersolubility of ceftazidime in water at different temperatures were measured by dynamic laser method,and the modified Tsuji equation and n equation were used to fit.The solubility and supersolubility of ceftazidime are little affected by temperature,but p H has a great influence on the solubility and supersolubility,which first decreases and then increases with the increase of p H.It provides data support for the study of crystallization kinetics and crystallization technology.Dynamic laser method was used to study the variation of ceftazidime with p H and the relationship between induction period and suoversaturation ratio.Based on the classical homogeneous nucleation theory,the interfacial tension,critical nucleation radius and nucleation free energy of solution were calculated,and the crystallization kinetics was studied by intermittent dynamic method.The particle size of the samples at different times was analyzed by Mastersizer 3000 laser particle size analyzer.Based on the particle count equation,the data were processed by moment transformation method.The crystal nucleation and growth rate models were obtained by regression.Through systematic experiments,the ceftazidime double feed crystallization process was developed,and the influence of different process conditions on the crystal habit and particle size distribution of the product was investigated.A table of optimized process operation conditions was obtained,that is,the initial crystallization liquid concentration was 0.33 g·g^-1,the feed liquid flow acceleration rate was 0.14 m L·min^-1,and the temperature was 27℃.The stirring rate was 250 r·min^-1.By using the optimized process,homogeneous flake ceftazidime crystals were prepared with intact crystal habit,median particle size of 184μm,diameter distance of 1.290,and yield of 80%..