Study On Reaction And Antisolvent Crystallization Of Cefoperazone Sodium

Cefoperazone sodium which is popularly applied in clinic from come into the marketis an antibiotic of cephalosporin. It possesses many merits, such as broad-spectrumantibiotic,lower toxicity,good curative effect. There are a lot of problems in productand quality. The cost of manufacture is higher, and the product's characters existobviously shortages comparing the foreign products, such as the content and crystalform. Hence, the systemic study on reaction-antisolvent crystallization ofcefoperazone sodium was carried out.The static method was used to measure the solubility of cefoperazone sodium atdifferent solvent ratios and different temperatures. The experimental data wasregressed in the form of λ-h equation by nonlinear least square. In the same time, themetastable zone was measured by laser. The study on thermodynamic is the base ofconfirming the process.The induction time of antisolvent crystallization was measured by naked eyeobservation, the induction time was short. The induction period in the presence ofultrasonic was determined and experimental evidences showed that ultrasonic can hasit reduced. Confirming the mechanism of nucleation of cefoperazone sodium inwater-acetone is chiefly polynucleation by analyzing the relation of lnS and lntind. Thesolid-liquid interface tension was estimated and frequently predicted the its theoreticalvalue. Furthermore the surface entropy was calculated and the growth mechanism ofCPZ was preliminarily disclosed. There was agglomeration-breakage in antisolventcrystallization of cefoperazone sodium, the agglomeration was obvious. The effect ofsupersaturation and stirring on agglomeration was chiefly discussed in this paper.Nucleation and growth kinetic parameters were measured by batch dynamic methods.In experimental conditions, the crystal of cefoperazone sodium showed manifestagglomeration, but breakage was not obvious. The kinetic data were treated with adiscretized population balance model. A size-independent growth and agglomerationrate model was established. The results demonstrated that the primary nucleation wasthe dominating mechanism; the growth of crystal was integration controlled.To obtain high quality product (excellent clarity and high purity) and yields, theeffects of reactive conditions (the reactive temperature, the final pH value and the摘要initial volume of water, et al) and crystallization conditions (such as the crystallizationtemperature, seed, addition rate of antisolvent, stir speed, breeding time and the finaltemperature of crystallization) on them were studied in detail, as a result, therelatively better operation schedule was found.The paper supplied the basic for the further study in the future and for industrialproduction. No similar research report has been published yet.