A Study On Crystal Transformation And Crystallization Process Of Cefodizime Sodium

Cefodizime disodium (CAS Registry No.86329-79-5) is one of the third generationof semi-synthetic antibiotics with extended antibacterial spectrum. Besides theadvantages of broad-spectrum antimicrobial activity and long pharmacodynamiceffects, it has the unique immunoregulatory activity compared to the other thirdgeneration antibiotics. This article aims at improving unsatisfactory crystal habit andnonuniform crystal size distribution (CSD) by optimizing dilution crystallizationprocess of cefodizime sodium which is of great value to industrial application.A series of non-isothermal desolvation kinetics models were established based onTG analysis data of cefodizime sodium solvate and explanations of desolvationmechanism was given correspondingly, which provide theoretical foundation fordrying process.The solubility data of both solvate and amorphous in water and ethanol mixedsolvent were measured with dynamic method. The data were correlated by threeequations including the Van’t Hoff, the modified Apelblat and the Jouyban Acreeequations respectively. All the data have laid thermodynamic foundation for bothcrystallization and crystal transformation process.A preliminary study of crystal transformation behavior of amorphous wasconducted by using in situ Raman and polarized light microscopy characterizationtechniques. Besides, the effects of temperature and seeding on transformation wereconsidered separately. It was proved that: increasing temperature can facilitatetransformation process; addition of seeding can significantly shorten the nucleationinduction period; the nucleation of the solvate is the control step of the process.In order to achieve high yield and fine crystal size distribution, several parametersincluding initial concentration, temperature, anti-solvent dosing rate and addition rate,seeding and crystallization method were tested respectively in the laboratory.Consequently, product with high yield and fine CSD was obtained.All the above content has never been reported by any related literatures.