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Preparation method of 6-ethylchenodeoxycholic acid composition

A technology of obeticholic acid and its composition, which is applied in the field of preparation of obeticholic acid composition and its tablet, can solve the problems of unfavorable industrial production, complex premixing process, and low production efficiency, and achieve simplified production process, The effect of stable quality and improved production efficiency

Active Publication Date: 2019-04-16
ZHEJIANG HUAHAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned premixing process is relatively complicated. The auxiliary materials used for premixing, microcrystalline cellulose (MCC) and carboxymethyl starch sodium (CMS-Na), need to be sieved with a 1.0mm aperture sieve in advance, and magnesium stearate needs to be used in advance Screening with a 0.5mm aperture screen; secondly, in the pre-mixing step, the microcrystalline cellulose is divided into multiple parts, and mixed with a specific amount of obeticholic acid and corresponding excipients in a specific order in stages. The steps are cumbersome, the process is complicated, and the production efficiency is high. Low, not conducive to large-scale industrial production

Method used

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  • Preparation method of 6-ethylchenodeoxycholic acid composition
  • Preparation method of 6-ethylchenodeoxycholic acid composition
  • Preparation method of 6-ethylchenodeoxycholic acid composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0115] Tablet formulation: obeticholic acid particle size D90 = 27 μm

[0116]

[0117] Preparation Process:

[0118] (1) Weigh microcrystalline cellulose, obeticholic acid, sodium starch glycolate, and pass through a 60-mesh sieve once;

[0119] (2) Add the above materials into the wet granulator, according to the set parameters, the rotation speed of the stirring paddle: 50rpm, the rotation speed of the cutting knife: 1000rpm, and mix for 7min;

[0120] (3) Magnesium stearate is added to the above-mentioned materials, in a wet granulator, mixed for 3 minutes at a stirring paddle speed of 50 rpm, to obtain a premix;

[0121] (4) Carry out dry granulation of the above premix, then add external pharmaceutical excipients microcrystalline cellulose and sodium starch glycolate to the square cone mixer, mix at 30rpm for 10min, and then add magnesium stearate , in a square-cone mixer, mixed for 3 minutes at a speed of 30 rpm to obtain a total mixture;

[0122] (5) Compress the...

Embodiment 2

[0124] Tablet formulation: obeticholic acid particle size D90 = 27 μm

[0125] Same as Example 1

[0126] Preparation process: The process is different: only the cutting knife is not turned on

[0127] (1) Weigh microcrystalline cellulose, obeticholic acid, sodium starch glycolate, and pass through a 60-mesh sieve once;

[0128] (2) Add the above materials into the wet granulator, according to the set parameters, the rotation speed of the stirring blade: 50rpm, the rotation speed of the cutting knife: 0rpm, and mix for 7min;

[0129] (3) Magnesium stearate is added to the above-mentioned materials, in a wet granulator, mixed for 3 minutes at a stirring paddle speed of 50 rpm, to obtain a premix;

[0130] (4) Carry out dry granulation of the above-mentioned premix, then add external pharmaceutical excipients microcrystalline cellulose and sodium starch glycolate in a square cone mixer, mix at 30rpm for 10min, and then add magnesium stearate , in a square-cone mixer, mixed fo...

Embodiment 3

[0133] Tablet formulation: obeticholic acid particle size D90 = 16 μm

[0134]

[0135] Preparation Process:

[0136] (1) Weigh microcrystalline cellulose, obeticholic acid, sodium starch glycolate, and pass through a 60-mesh sieve once;

[0137] (2) Add the above materials into the wet granulator, according to the set parameters, the rotation speed of the stirring blade: 50rpm, the rotation speed of the cutting knife: 0rpm, and mix for 7min;

[0138] (3) Magnesium stearate is added to the above-mentioned materials, in a wet granulator, mixed for 3 minutes at a stirring paddle speed of 50 rpm, to obtain a premix;

[0139] (4) Carry out dry granulation of the above-mentioned premix, then add the external pharmaceutical excipient carboxymethyl starch sodium in a square cone mixer, mix at a speed of 30rpm for 10min, then add magnesium stearate, and mix in a square cone mixer. In the mixer, mix at 30rpm for 3min to obtain the total mixture;

[0140] (5) Compress the above bl...

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Abstract

The invention provides a preparation method of a 6-ethylchenodeoxycholic acid composition. The composition is composed of 6-ethylchenodeoxycholic acid and pharmaceutically acceptable adjuvant. The preparation method comprises the steps that the 6-ethylchenodeoxycholic acid and the pharmaceutical adjuvant are premixed through a wet granulation pot, and then dry granulation is carried out to obtainthe 6-ethylchenodeoxycholic acid composition. The preparation method of the 6-ethylchenodeoxycholic acid composition has the advantages that the problem that the complete dissolution at the end of anin-vitro dissolution experiment is more dependent on the particle size of the 6-ethylchenodeoxycholic acid and the mixing process is effectively solved, the production process is simplified, the production efficiency is improved, and the preparation method is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of an obeticholic acid composition and a tablet thereof. Background technique [0002] Obeticholic acid (obeticholic acid) is an orally active analogue of the natural human bile acid CDCA (chenodeoxycholic acid) developed by Intercept Pharmaceuticals (Genextra), as a class of farnesoid X receptor (FxR) agonists, It can be used to treat primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), alcoholic hepatitis and primary sclerosing cholangitis (PSC). The chemical name of obeticholic acid is: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid. The CAS registry number for obeticholic acid is 459789-99-2. Its molecular structural formula is as follows: [0003] [0004] Obeticholic acid is sensitive to heat and humidity. In the prior art, a dry granulation process is generally used to prepare obeticholic acid compositions and prepar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/36A61K31/575A61P1/16
CPCA61P1/16A61K9/2866A61K31/575Y02A50/30
Inventor 聂倩兰彭俊清黄日沈广青陆竞胡李斌章正赞张家艾
Owner ZHEJIANG HUAHAI PHARMA CO LTD