Preparation process of azilsartan micro-powder raw material drug

A technology of preparation process and raw material medicine, applied in the direction of organic chemistry, etc., can solve the problems of cumbersome crushing process operation, increased impurities, and difficulty in micronization of azilsartan raw material medicine

Active Publication Date: 2018-11-09
ZHEJIANG HONGYUAN PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method solves the problem of increasing impurities in the raw material drug process, the stability of the raw material drug after mechanical pulverization has not been solved
Moreover, the crushing process is cumbersome to operate, and needs to be fed in multiple batches, and liquid nitrogen needs to be continuously added during the crushing process
At the same time, the micro-grinding process also has the following defects: on the one hand, the long-term work under the ultra-low temperature of liquid nitrogen greatly shortens the s...

Method used

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  • Preparation process of azilsartan micro-powder raw material drug
  • Preparation process of azilsartan micro-powder raw material drug
  • Preparation process of azilsartan micro-powder raw material drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Get 100g of azilsartan bulk drug and place it in the RF-08 type high-speed pulverizer, pulverize intermittently for 2 minutes, and the HPLC and particle size of the gained azilsartan micropowder sample are shown in the following table:

[0050]

Embodiment 2

[0052] Get 100g azilsartan crude drug and place it in the RF-08 type high-speed pulverizer, pulverize intermittently for 5 minutes, and the obtained azilsartan micropowder sample HPLC and particle size are shown in the following table:

[0053]

[0054] B, the process described in the present invention

Embodiment 3

[0056] Put 25.0g of azilsartan raw material drug and 100ml of tetrahydrofuran into a reaction bottle, heat to 60-70°C and stir for 1 hour, then place the suspension to cool down to 20-30°C, filter, and wash the filter cake with 50ml of tetrahydrofuran to obtain The filter cake was dried under reduced pressure at 30-40° C. to obtain 26.1 g of dispersed azilsartan. Put the dispersed azilsartan and 1430ml of acetone into a 2L reaction bottle, heat to 55-65°C to dissolve, then distill 620ml of acetone, after the distillation, cool down to 25-30°C at a rate of 10°C / hour, and Stir at 25-30°C for 1 hour, then lower the temperature to 0-5°C, keep stirring at 0-5°C for 2 hours, filter, wash the filter cake with 50ml of cold acetone, and dry it in vacuum at 30-40°C to obtain Azisa Tan 23.7g, yield 94.8%. HPLC purity and particle size are shown in the table below:

[0057]

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PUM

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Abstract

The invention provides a process for controlling the particle size of an azilsartan raw material drug by virtue of solvent dispersion and crystal combination methods. According to the process, the micronization of the azilsartan raw material drug is realized. The preparation process is high in yield and simple and convenient to operate, the micronized product is good in stability, the particle size of the micronized raw material drug can meet the particle size requirement in a preparation prescription process, namely D(90) is not more than 20 microns, and the process is suitable for industrialproduction.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical engineering and drug crystallization, and in particular relates to a preparation process of azilsartan micropowder bulk drug. Background technique [0002] Azilsartan, chemical name: 2-ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl ) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid, the structure of which is shown in formula I. Azilsartan is an angiotensin Ⅱ receptor antagonist developed by Takeda Pharmaceutical Co., Ltd. of Japan. It was approved for marketing in Japan in 2012 and is mainly used clinically for the treatment of hypertension. Compared with candesartan cilexetil, the clinical efficacy and side effects of azilsartan show stronger advantages, and it is regarded as the next-generation product of candesartan cilexetil, which has a very good market prospect. [0003] [0004] Azilsartan bulk drug is almost insoluble in water. In the biopharmaceutical (BCS) classi...

Claims

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Application Information

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IPC IPC(8): C07D413/10
CPCC07D413/10
Inventor 汪海波金辉梅光耀王凯明况洪福黄仕情徐陈力林金荣林京都覃松刘阳
Owner ZHEJIANG HONGYUAN PHARMA
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