Preparation method of cefotaxime sodium spherical crystals

Abstract

The invention discloses a preparation method of cefotaxime sodium spherical crystals. The preparation method comprises the following steps: preparing a mixed solution of water-organic solvent at 10 to30 DEG C, wherein water and an organic solvent are in the mass ratio of (1 to 1) to (1 to 5); then, preparing a mixed solution of cefotaxime sodium-water-organic solvent with the cefotaxime sodium concentration of 0.1 to 0.3 g / mL; adding a bridging agent, adding cefotaxime sodium seed crystals, and stirring for 5 to 60 minutes; adding the same organic solvent as the organic solvent in the mixed solution dropwise, continuing stirring until crystals separate out, and after the organic solvent is added completely, keeping stirring for 0.1 to 5 hours so that crystals aggregate into spheres; filtering, washing and drying to obtain the cefotaxime sodium spherical crystals. A crystallizing process does not have a gelatinizing phenomenon; the average particle size of a spherical crystal product is about 100 to 200 microns; the crystal particles are mellow and full; the fluidity is high; the tap density is 0.3 to 0.4 g / cm<3>. The product can be subjected to tabletting directly; granulating anddrying processes are omitted; the cost is reduced.

Description

technical field [0001] The invention belongs to the technical field of chemical engineering industrial crystallization, and in particular relates to a preparation method of spherical cefotaxime sodium crystals. Background technique [0002] Cefotaxime sodium (CAS: 64485-93-4), also known as ceftaxime, cefotaxime, etc., is a third-generation semi-synthetic cephalosporin antibiotic. Molecular formula C 16 h 16 N 5 NaO 7 S 2 , molecular weight 477.45, usually white or slightly yellow crystal or powder, odorless or slightly special odor. Soluble in water, slightly soluble in ethanol, insoluble in high alcohols, chloroform, hexane, diethyl ether and ethyl acetate, etc. Cefotaxime sodium is a third-generation cephalosporin antibiotic for injection, which was jointly developed by three companies (French Roussel, Germany Hearst and Japan Chugai Pharmaceutical Company), and was first listed in Germany in 1980. Listed in many countries around the world. [0003] The preparatio...

AI Technical Summary

Problems solved by technology

The methods disclosed in patents CN101486719A, CN102584854A, and CN103319504A cause explosive nucleation due to high supersaturation during operation, which eventually leads to gelation, which seriously affects the stirring and mixing effect and the quality of crystal products

The methods disclosed in patents CN103275101A and WO2004063203A1 have harsh control conditions, numerous operating steps, and complex mixed solvent systems, which are not conducive to industrialization

Different from the above-mentioned method, the method disclosed in the patent CN104892636B obtains a crystalline product by statically transforming the cefotaxime sodium amorphous powder in a specific atmosphere. Although the operation is simple and there is no gel problem, the surface of the product has obvious burrs, which will It leads to decreased fluidity and low bulk density, which makes it difficult for the downstream preparation process

In summary, the main problems of cefotaxime sodium products at present are: easy gelation during the preparation process, poor shape of the final product, and low bulk density

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