Study On The Reactive Crystallization Process Of Chlortetracycline Hydrochloride

Chlortetracycline hydrochloride(CTC) is a kind of tetracycline antibiotics. Isomeric compounds create inevitably in different conditions of the producing process and CTC has different valid content. CTC is unstable in neutral and alkaline environment, since it can be changed into its isomer and lose its antibacterial effect. The present crystallization technology of CTC makes its product has such problems as purity, granularity and so on. The reaction crystallization process of CTC in ethanol was studied systematically, including the crystallization thermodynamics, the crystallization kinetics, optimizing the crystallization process and studying effective factors of the CTC's impurity absorbency.In the study of crystallization thermodynamics, the solubility of CTC in ethanol with water content of 10%~90% was measured respectively at 25℃~40℃. The supersolubility data were calculated by material balance equation and the metastable zone was confirmed.The effective factors of the CTC's impurity absorbency were also studied systematically. Based on the conditions which affect the rate of degradation, it found the main factors affecting the absorbency of CTC and provided academic base for the process optimization.In the study of crystallization kinetics, the kinetic data were experimentally measured with intermittent dynamic method and the nucleation rate and growth rate equation were obtained by the regression method.Based on the crystallization thermodynamics and the crystallization kinetics, some contradistinctive experiments were made to optimize the crystallization process. The effect factors on the crystal habit or CSD were studied including the temperature of crystallization system, the crystallization schedule, the concentration of hydrochloric acid, the feed rate of hydrochloric acid, seeding and agitation intensity. The optimized conditions of CTC crystallization process were found.This article studied systematically the crystallization process of CTC under the optimized operation conditions. The crystal obtained by experiments accord with the crystal of factory at absorbency, content, ratio of reclaim and are better than the factory at CSD and crystal habit. The result can be provided to further production. Data of solubility and kinetics have not been reported.