Study On Crystallization Process Of Cefaclor

As second generation of cephalosporins,Cefaclor has the advantages of cheap price,broad-spectrum antisepsis,low renal toxicity,and become a common drug in China.Cefaclor inhibitings the final step synthesis of the cell wall by interdicting the cross bonding of mucopeptide.At present,in industrial manufacture of the Cefaclor,the poor quality of the product was caused by small particle size,lack of production stability and significant differences between zones,which become the bottleneck of large-scale production.Therefore,my thesis' s point is the systematic study on the crystallization process of Cefaclor.The crystal morphology of Cefaclor was studied.Materials Studio(MS)was used to simulate the crystal cell parameters and obtains microstructure,which bases on crystal structure data collected by X-ray diffraction technique.The theoretical crystal habit of cefaclor is predicted by BFDH and AE model,and the AE model is closed to the observed morphology.The thermodynamics of Cefaclor was studied.The solubility of Cefaclor in four pure solvents(water,methanol,ethanol,acetone),three mixed solvents(water–methanol,water–ethanol,water–acetone mixtures)and different pH aqueous solution were measured using a dynamic laser monitoring technique under different temperatures.The solubility data was fittingly correlated by the modified Apelblat,modified R-K model,combined nearly ideal binary solvent/Redlich–Kister model and Jouyban–Acree model.The standard enthalpy,entropy and Gibbs free energy change of Cefaclor were calculated to obtain thermodynamics data which is related to cefaclor crystallization.The basic data were obtained by thermodynamics study for crystallization kinetics and new crystallization process.The crystallization kinetics of Cefaclor had been studied.Nucleation and growth kinetic parameters were measured by batch dynamic methods under different crystallographic systems.The grain sizes of production were analyzed by Mastersizer3000 in the samples of crystallographic progress.Dynamic model of the cefaclor was established based on the mass balance equation and population balance equation,without the heat balance.Applying moment transformation method,the mathematical models for crystal growth rate and secondary nucleation rate was obtained,and the operating parameters which effectted the crystallographic progress were analyzed.Based on the investigation of Cefaclor crystal morphology,crystallization thermodynamics and dynamics,a new crystallization technology was developed in this thesis.The effects of different operation conditions on the crystallization process and the quality of product were investigated,and the optimal operation strategy was established.The technology has been applied in industrial production after industrial scale-up.No same report to above study results has been published in literature up to date.