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Rabeprazole sodium anhydride crystal form and preparation method thereof

A technology of rabeprazole sodium and anhydrate, which is applied in the field of rabeprazole sodium anhydrate crystal form and preparation thereof, can solve the problems of poor stability and no crystal form, and achieves good stability, stable quality, good effect

Active Publication Date: 2021-09-03
湖南德虹制药有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It can be seen from this that the existing rabeprazole sodium has a crystal form and is basically a non-anhydrous substance. Although rabeprazole sodium is amorphous and anhydrous, it has no crystal form and has poor stability.
Through market research, there is currently no rabeprazole sodium crystalline anhydrate supply in the market. In order to ensure the quality stability of rabeprazole sodium-related preparations, it is necessary to develop a stable rabeprazole sodium anhydrous crystal type

Method used

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  • Rabeprazole sodium anhydride crystal form and preparation method thereof
  • Rabeprazole sodium anhydride crystal form and preparation method thereof
  • Rabeprazole sodium anhydride crystal form and preparation method thereof

Examples

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Effect test

Embodiment 1

[0040] A kind of rabeprazole sodium anhydrate crystal form of the present invention, the mass percent of water in the rabeprazole sodium anhydrate crystal form is 0.31%, in X-ray powder diffraction represented by CuKa radiation, 2θ angle In the spectrum, the rabeprazole sodium anhydrate crystal form has the 2θ diffraction angle and d value shown in Table 1 below.

[0041] The XRD characteristic of the rabeprazole sodium anhydrate crystal form of table 1 embodiment 1

[0042]

[0043]

[0044] A preparation method of the rabeprazole sodium anhydrate crystal form of the present embodiment, comprising the following steps:

[0045] (1) Add 50mL of methanol into a 250mL three-necked flask, then add 10.00g of rabeprazole (0.027mol) and 1.12g of sodium hydroxide (0.027mol), stir at room temperature for 3 hours, and reduce The methanol solvent was removed by pressure distillation and evaporated to dryness to obtain 10.08 g of rabeprazole sodium with a water content of 1.05%.

...

Embodiment 2

[0059] A kind of rabeprazole sodium anhydrate crystal form of the present invention, the mass percent of water in the rabeprazole sodium anhydrate crystal form is 0.35%, in X-ray powder diffraction represented by CuKa radiation, 2θ angle In the spectrum, the crystalline form of rabeprazole sodium anhydrate has the 2θ diffraction angles and d values ​​shown in Table 5 below.

[0060] The XRD characteristic of the rabeprazole sodium anhydrate crystal form of table 5 embodiment 2

[0061]

[0062]

[0063] A preparation method of the rabeprazole sodium anhydrate crystal form of the present embodiment, comprising the following steps:

[0064] (1) Add 50mL of methanol into a 250mL three-necked flask, then add 10.00g of rabeprazole (0.027mol) and 1.12g of sodium hydroxide (0.027mol), stir at room temperature for 3 hours, and reduce The methanol solvent was removed by pressure distillation and evaporated to dryness to obtain 10.14 g of rabeprazole sodium with a water content o...

Embodiment 3

[0067] A method for preparing rabeprazole sodium anhydrate crystal form of the present invention, step (1) is basically the same as Example 2, the only difference is: in step (2), 10.03g obtained in step (1), Rabeprazole sodium with a water content of 0.92% was dissolved by adding 30 mL of a mixed solvent of dichloromethane and isopropyl acetate, wherein the volume ratio of dichloromethane to isopropyl acetate was 0.5:10. This embodiment obtains 9.35g rabeprazole sodium anhydrate crystal form, and the detected water content is 0.27%, and the XRD figure is as follows Figure 5 Shown, instrument and test condition are with embodiment 2.

[0068] The XRD characteristic of the rabeprazole sodium anhydrate crystal form of table 6 embodiment 3

[0069]

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Abstract

The invention discloses a rabeprazole sodium anhydride crystal form and a preparation method thereof. The rabeprazole sodium anhydride crystal form shows characteristic diffraction peaks at 4.769 degrees, 14.207 degrees, 17.174 degrees, 18.021 degrees, 19.486 degrees and 26.5 degrees in an X-ray powder diffraction pattern represented by CuKa radiation and an angle of 2[theta] + / -0.2 degrees, and the water content is less than 1%. The preparation method comprises the steps of dissolving rabeprazole and sodium hydroxide in methanol or acetone to form salt to obtain rabeprazole sodium, adding a mixed solution of dichloromethane and esters, cooling to -30 to -10 DEG C under the protection of nitrogen, and crystallizing to obtain the rabeprazole sodium anhydride crystal form. The rabeprazole sodium anhydride crystal form has the advantages of low moisture content, high stability, high quality safety and the like, and can better ensure the quality stability of rabeprazole sodium related preparations.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a rabeprazole sodium anhydrate crystal form and a preparation method thereof. Background technique [0002] Rabeprazole sodium (Rabeprazole Sodium) is the sodium salt of rabeprazole, its chemical name is: 2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl] Methylsulfinyl}-1H-benzimidazole sodium, its structural formula is: [0003] [0004] Rabeprazole sodium is a proton pump inhibitor with a high pKa value, which is rapidly activated in vivo and inhibits the H + / K + -ATPase activity, thereby inhibiting the secretion of gastric acid. Clinically, it is mainly used to treat peptic ulcer, gastroesophageal reflux disease, Zoller-Ellison syndrome and other diseases. It was first listed in Japan in 1997, and then listed in Europe, the United States, and China. At present, there are many research reports on amorphous rabeprazole and its sodium salt in the literature, but there are ...

Claims

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Application Information

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IPC IPC(8): C07D401/12
CPCC07D401/12C07B2200/13
Inventor 夏钊王成廖志勇其他发明人请求不公开姓名
Owner 湖南德虹制药有限公司