Study On Enzymatic Synthesis And Crystallization Of Cephalexin Monohydrate

Cephalexin monohydrate,a kind of first-generation cephalosporin,has been currently one of the world’s largest consumption of cephalosporin antibiotics,thus it plays an important role in medical industry.The traditional chemical synthesis of cephalexin monohydrate has lots of disadvantages.For example,the process is of complex procedures with long reaction time and requires large amounts of organic solvents.However,with water as the solvent,enzymatic synthesis of cephalexin monohydrate has many advantages.For example,it requires mild reaction conditions,its operation is simple with no group protection,and it is clean and safe etc.So it has great practical value and broad prospects for industrial applications.In this paper,the synthesis and recrystallization of enzymatic synthesis of cephalexin monohydrate have been systematically studied,which aims at improving product quality and overall process yield.Moreover,this study provides a theoretical reference and data foundation for the development of its industrial-scale production.The study on the synthesis of enzymatic synthesis of cephalexin monohydrate measured the effects of the feeding mode,the material ratio,the mass of enzyme,the reaction temperature,the reaction p H,the reaction time and other technological parameters on products’ yield and quality.The optimum reaction conditions were obtained by single factor test and orthogonal test.The purity of the optimal experimental product was more than 99.8% with the yield more than 93.5%.As the function of p H,the solubility of cephalexin monohydrate in water was obtained by using laser dynamics method at 283.15 K,293.15 K,303.15 K and then were correlated.The solubility of cephalexin monohydrate in methanol-water and acetone-water mixtures was determined by using a static equilibrium method and a high-performance liquid chromatography technique under atmospheric pressure at temperatures ranging from 278.15 K to 308.15 K.The solubility data were correlated using the modified Apelblat,the combined nearly ideal binary solvent/Redlich-Kister,the Jouyban-Acree and the non-random two-liquid models.The Akaike information criterion(AIC)was used to compare the relative applicabilities of these models in binary solvent system.The enthalpy,entropy,and Gibbs free energy of dissolution process of cephalexin monohydrate in binary solvent system were calculated.The above studies provided the basic data for the crystallization of cephalexin monohydrate,and these solubility data and models were of great significance for the development and optimization of the enzymatic synthesis of cephalexin monohydrate.Recrystallization process is one of the main methods of medication purification.The process is relevant to the crystal form and the quality of the product.In order to get higher yield and better crystal form of cephalexin product,the study on the recrystallization of enzymatic synthesis of cephalexin monohydrate measured the effects of the adding rate of mother liquor,stirring speed,the amount of seed,the crystallization temperature and other technological parameters on products’ yield,particle size and distribution.Then the optimized recrystallization conditions were obtained,the product yield of the optimized recrystallization technology was 85%,the purity was larger than 99.8%,and the particle size and distribution were greatly improved compared with traditional method before optimization.