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Levofloxacin hydrochloride crystal forms and preparation methods thereof

A technology of levofloxacin hydrochloride and crystal form, which is applied in the field of medicinal chemistry and achieves the effects of good fluidity, great application value and good solubility

Active Publication Date: 2012-10-24
SHANGYU JINGXIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But, so far, there are no related patents, bibliographical reports on the crystal form of levofloxacin hydrochloride formula II

Method used

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  • Levofloxacin hydrochloride crystal forms and preparation methods thereof
  • Levofloxacin hydrochloride crystal forms and preparation methods thereof
  • Levofloxacin hydrochloride crystal forms and preparation methods thereof

Examples

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Embodiment 1

[0046] Embodiment 1: Preparation of levofloxacin hydrochloride crystal form I

[0047]Method A: Weigh 5g of levofloxacin hydrochloride sample, put it into a round bottom flask, add 25mL of 75% ethanol aqueous solution, heat to 70°C and reflux until completely dissolved. After natural cooling, white crystals precipitated, continued cooling, and the crystallization stopped at 20°C. Suction filtration, drying at 30-40°C.

[0048] Method B: Weigh 10 g of levofloxacin hydrochloride sample, put it into a round bottom flask, add 100 mL of 50% isopropanol aqueous solution, heat to 70° C. and reflux until completely dissolved. Cool in an ice-water bath, white crystals precipitate out, continue to cool, and stop crystallization at 20°C. Suction filtration, drying at 30-40°C.

[0049] Method C: Weigh 5g of levofloxacin hydrochloride sample, put it into a round bottom flask, add 30mL of 80% aqueous methanol solution, heat to 60°C and reflux until completely dissolved. Natural cooling,...

Embodiment 2

[0050] Embodiment 2: preparation method of levofloxacin hydrochloride crystal form II

[0051] Method A: Weigh 2g of levofloxacin hydrochloride sample, put it into a round bottom flask, add 40mL of methanol solution, heat to 60°C and reflux until completely dissolved. After natural cooling, yellowish crystals precipitated, continued cooling, and the crystallization stopped at 20°C. Suction filtration, drying at 80-90°C.

[0052] Method B: Weigh 2 g of levofloxacin hydrochloride sample, add it to a round bottom flask, add 40 mL of methanol and ethanol mixed solution (the ratio of methanol to ethanol is 3:1), heat to 60 ° C and reflux until completely dissolved. After natural cooling, yellowish crystals precipitated, and the cooling continued until the crystallization stopped at 20°C. Suction filtration, drying at 80-90°C.

[0053] Method C: Weigh 10 g of levofloxacin hydrochloride sample, add it to a round bottom flask, add 240 mL of a mixed solution of methanol and acetone ...

Embodiment 3

[0055] Embodiment 3: preparation method of levofloxacin hydrochloride crystal form III

[0056] Method A: Weigh 2g of sample, put it into a round bottom flask, add 4.5mL of 60% isopropanol, heat to 75°C and reflux until completely dissolved. After natural cooling, white crystals precipitated, cooled to room temperature, and continued to stir for 30 minutes to stop the crystallization. Suction filtration, drying at 60-70°C.

[0057] Method B: Weigh 5g of sample, put it into a round bottom flask, add 25mL of 75% ethanol, heat to 75°C and reflux until completely dissolved. Cool naturally, white crystals precipitate, cool to room temperature, continue to stir for 30 minutes, stop crystallization and suction filtration, and dry at 60-70°C.

[0058] The structural characterization of levofloxacin hydrochloride crystal forms I, II, and III prepared by the above method is as follows:

[0059] The structural characterization of the levofloxacin hydrochloride crystal form I prepared ...

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Abstract

The invention discloses new levofloxacin hydrochloride crystal forms comprising a crystal form I, a crystal form II and a crystal form III. The differential scanning calorimetric graph of the crystal form I has two endothermic peaks at 20-120DEG C and one exothermic peak at 200-250DEG C, and the thermogravimetric graph of the crystal form I shows that one crystal water is contained; the differential scanning calorimetric graph of the crystal form II has one endothermic peak at 260-300DEG C, and the thermogravimetric graph of the crystal form II shows that no crystal water is contained; and the differential scanning calorimetric graph of the crystal form III has one endothermic peak at 50-120DEG C, one exothermic peak at 200-220DEG C and one endothermic peak at 270-300DEG C, and the thermogravimetric graph of the crystal form III shows that half crystal water is contained. The three levofloxacin hydrochloride crystal forms are better than existing levofloxacin hydrochloride crystal forms, have the characteristics of good stability, good fluidity, difficult water absorption and deliquescence, and the like, has the advantages of good solubility, easy preparation production, and long term storage, and has large medicinal application values. The invention provides preparation methods of the crystal forms.

Description

technical field [0001] The present invention relates to medicinal chemistry, in particular to levofloxacin hydrochloride crystals and a preparation method thereof, in particular to stable crystal form I containing one crystal water, crystal form III containing half a crystal water, and anhydrous levofloxacin hydrochloride crystal form II and preparation thereof method. Background technique [0002] Levofloxacin, (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7Hpyridine[1, 2,3-de]-[1,4]benzoxazine-6-carboxylic acid. Usually it is the free form shown in formula A and levofloxacin hydrochloride shown in formula B ((S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(4 -Methyl-1-piperazinyl)-7-oxo-7H-pyridine[1,2,3-de]-[1,4]benzoxazine-6-carboxylate hydrochloride) form, which in this is well known in the field. [0003] [0004] Levofloxacin is the L-body of ofloxacin, its antibacterial activity is about twice that of ofloxacin, and it has broad-spectrum ant...

Claims

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Application Information

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IPC IPC(8): C07D498/04
Inventor 胡秀荣金志平黄悦王伟强
Owner SHANGYU JINGXIN PHARMA
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