Crystal form of flomoxef sodium, preparation method, pharmaceutical composition and application

A technology of sodium fluoxefaclor and a composition, applied in the field of drug crystals, can solve the problems of inability to be removed by drying, no clear disclosure of the crystal form of sodium fluoxefate, and organic solvents affecting medicinal value, etc., and achieve the advantage of good stability Effect

Active Publication Date: 2020-05-22

泊诺(天津)创新医药研究有限公司

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AI-Extracted Technical Summary

Problems solved by technology

However, fluoxetal sodium is easy to form solvated crystals with organic solvents such as dichloromethane, ethyl acetate, methanol, etc., which cannot be removed by drying, a...

Abstract

The invention provides a crystal form of flomoxef sodium. An X-ray diffraction pattern of the crystal form comprises X-ray diffraction peaks as shown in the following 2[theta] angles: 5.2 +/-0.2 degrees and 16.2 +/-0.2 degrees. In addition, the invention also discloses a preparation method of the crystal form compound, a pharmaceutical composition and application of the crystal form compound and the pharmaceutical composition in preparation of anti-bacterial infection drugs. Compared with an amorphous product prepared by a freeze-drying process, the novel crystal form obtained by the preparation method disclosed by the invention has the advantages that the stability of the novel crystal form is obviously superior to that of the amorphous form, which means that the crystal form disclosed bythe invention has less degradation impurity generation and lower drug storage condition requirements within the validity period, and has a good medicinal use prospect.

Application Domain

Antibacterial agentsOrganic active ingredients +1

Technology Topic

Chemical compoundFlomoxef +9

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Examples

Experimental program(11)

Example Embodiment

[0050] Example 1

[0051] Add 40 grams of fluoxefic acid to a mixed solvent of 400 ml of ethylene glycol and 400 ml of isobutanol, and stir to dissolve. Add 5% (W/W) sodium bicarbonate aqueous solution dropwise with stirring to adjust the pH to 4.5-6.0. Then, it was stirred and cooled to -10°C, and the stirring was continued for 5 hours to crystallize. The suspension was filtered, and the obtained crystals were washed with isobutanol, and dried under vacuum at 25°C to a constant weight to obtain 26.6 grams of white granular crystals of fluoxef sodium. The purity of the crystal form obtained in this example was 98.4% measured by high performance liquid chromatography HPLC.

Example Embodiment

[0052] Example 2

[0053] Add 20 g of fluoxefic acid to a mixed solvent of 150 ml of ethylene glycol and 150 ml of isobutanol, and stir to dissolve. While stirring, add dropwise about 8% (W/W) sodium bicarbonate aqueous solution to adjust the pH to 4.5-6.0. Then cool down to -15°C with stirring, continue stirring to crystallize for 5 hours, filter the suspension, wash the obtained crystals with isobutanol, and dry under vacuum at 25°C to a constant weight to obtain 15.8 g of white granular crystals of fluorooxef sodium The purity of the crystal form obtained in this example was 99.1% as measured by high performance liquid chromatography HPLC.

Example Embodiment

[0054] Example 3

[0055] Add 50 grams of fluoxefic acid to a mixed solvent of 375 ml of ethylene glycol and 375 ml of isobutanol, and stir to dissolve. Under stirring, about 10% (W/W) sodium bicarbonate aqueous solution (a saturated solution stirred at 25° C. for 1 hour) was added dropwise to adjust the pH to 4.5-6.0. Then cool down to -20°C with stirring, continue stirring to crystallize for 5 hours, filter the suspension, wash the obtained crystals with isobutanol, and vacuum dry at 25°C to a constant weight to obtain 40.1 grams of white granular crystals of oxycephalosporin sodium The purity of the crystal form obtained in this example is 99.6% measured by high performance liquid chromatography HPLC.

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Description & Claims & Application Information

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