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Rabeprazole sodium anhydrate 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 its preparation, can solve the problems of no crystal form and poor stability, and achieve stable quality, good stability, The effect of enhanced thermal stability

Active Publication Date: 2022-06-24
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 anhydrate crystal form and preparation method thereof
  • Rabeprazole sodium anhydrate crystal form and preparation method thereof
  • Rabeprazole sodium anhydrate crystal form and preparation method thereof

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Embodiment 1

[0040] A rabeprazole sodium anhydrate crystal form of the present invention, the mass percentage of water in the rabeprazole sodium anhydrate crystal form is 0.31%, and the X-ray powder diffraction represented by CuKa radiation and 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 characteristics of the rabeprazole sodium anhydrate crystal form of Table 1 Example 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 50 mL of methanol to a 250 mL three-necked flask, then add 10.00 g of rabeprazole (0.027 mol) and 1.12 g of sodium hydroxide (0.027 mol), stir at room temperature for 3 hours, and reduce the temperature at 20°C to 30°C. The methanol solvent was removed by pressure distillation and evaporated to dryness to obtain 10.08 g of rabeprazole so...

Embodiment 2

[0059] A rabeprazole sodium anhydrate crystal form of the present invention, the mass percentage of water in the rabeprazole sodium anhydrate crystal form is 0.35%, and the X-ray powder diffraction represented by CuKa radiation and 2θ angle In the spectrum, the rabeprazole sodium anhydrate crystal form has the 2θ diffraction angle and d value 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 50 mL of methanol to a 250 mL three-necked flask, then add 10.00 g of rabeprazole (0.027 mol) and 1.12 g of sodium hydroxide (0.027 mol), stir at room temperature for 3 hours, and reduce the temperature at 20°C to 30°C. The methanol solvent was removed by pressure distillation and evaporated to dryness to obtain 10.14 g of rabeprazole ...

Embodiment 3

[0067] A preparation method of rabeprazole sodium anhydrate crystal form of the present invention, step (1) is basically the same as embodiment 2, the difference is only: in step (2), the 10.03g obtained in step (1), 30 mL of a mixed solvent of dichloromethane and isopropyl acetate was added to rabeprazole sodium with a water content of 0.92% for dissolution, wherein the volume ratio of dichloromethane and isopropyl acetate was 0.5:10. In this example, 9.35 g of rabeprazole sodium anhydrate crystal form was obtained, and the detected water content was 0.27%. The XRD pattern is as follows Figure 5 As shown, the apparatus and test conditions were the same as in Example 2.

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

[0069]

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Abstract

The invention discloses a rabeprazole sodium anhydrate crystal form and a preparation method thereof. The rabeprazole sodium anhydrate crystal form has an X-ray powder diffraction pattern represented by CuKa radiation and an angle of 2θ±0.2° It shows characteristic diffraction peaks at 4.769°, 14.207°, 17.174°, 18.021°, 19.486°, 26.510°, and the water content is <1%. The preparation method includes dissolving rabeprazole and sodium hydroxide in methanol or acetone to form a salt to obtain rabeprazole sodium, then adding a mixed solution of dichloromethane and esters, and cooling down to -30°C to -30°C under nitrogen protection. Crystallization was carried out at 10°C to obtain the anhydrous crystal form of rabeprazole sodium. The rabeprazole sodium anhydrate crystal form of the present invention has the advantages of low water content, high stability, high quality and safety, and can better ensure the stable quality 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 and is rapidly activated in vivo by inhibiting the H + / K + -ATPase activity, thereby inhibiting gastric acid secretion. Clinically, it is mainly used for the treatment of peptic ulcer, gastroesophageal reflux disease, Zollinger-Ellison syndrome and other diseases. It was first listed in Japan in 1997, and then in Europe, the United States, and China. At present, there are many research reports on amorphous rabeprazole and its sodium salts in the literature, but relatively...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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