Novel crystal form of cefazolin sodium and preparation method thereof

Abstract

The invention relates to a novel crystal form of cefazolin sodium and a crystallization preparation method thereof. An X-ray powder diffraction pattern is used for defining at the characteristic peaks of a diffraction angle of 2-theta degrees and DSC. The preparation method comprises the following steps: adding a cefazolin sodium solid into a solvent to prepare a suspension of 0.3-0.7g / mL; heating the suspension to 30-45 DEG C under a stirring condition; stirring for 0.5-12 hours at a constant temperature; cooling to 0-20 DEG C, and growing a crystal at a constant temperature for 0.5-2 hours; then filtering to obtain crystal slurry; and drying the filter cake obtained by filtering to obtain a product of the novel crystal form of cefazolin sodium. The novel crystal form has a higher heat-absorption temperature, the product purity, color and shape do not change after the product is stored for 100 days under a normal-temperature and dry condition, and the crystal form has relatively good stability. Compared with already reported crystal forms, the short-bar shaped novel crystal form has the advantages of relatively high dissolving speed and relatively high fluidity and bulk density, and is easy for commercially industrial large-scale implementation.

Description

technical field [0001] The invention belongs to the technical field of medicine separation, and in particular relates to a new crystal form of cefazolin sodium and a preparation method thereof. Background technique [0002] Cefazolin sodium (cefazolin sodium), its chemical name is (6R,7R)-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfur]methyl]-7 -[(1H-tetrazol-1-yl)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt. Molecular formula: C 14 h 13 N 8 NaO 4 S 3 , with a molecular weight of 476.50. The structural formula is shown in the figure below: [0003] [0004] Cefazolin sodium is a semi-synthetic cephalosporin antibiotic widely used clinically at present, and it is a broad-spectrum antibiotic. It has antibacterial activity against most Gram-positive and Gram-negative bacteria in vivo, but is ineffective against Pseudomonas aeruginosa; it has antibacterial activity against penicillinase-producing bacteria, Staphylococcus aureus in vit...

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Problems solved by technology

[0006] The above-mentioned patents and literature reports are mainly crystalline forms of cefazolin sodium containing crystal water. These crystalline forms are easy to dehydrate or absorb moisture under certain temperature and pressure and transform into each other, so the requirements for drying and storage conditions are relatively high. At the same time During the long-term storage process, the product quality may fluctuate or change due to the transformation of the crystal form

Another amorphous form of cefazolin sodium reported in the above-mentioned patent is the solid form with the highest thermodynamic energy, so it also has problems such as poor thermal stability and irregular appearance of the product.

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