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Method for preparing amorphous atorvastatin calcium

An atorvastatin calcium, amorphous technology, applied in the direction of organic chemistry and other directions, can solve the problems of large impact on product quality, large solvent residue, large amount of solvent, etc., and achieves low production cost, high crystal form purity, and relatively easy remove effect

Inactive Publication Date: 2009-07-29
ZHEJIANG JINGXIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Too many solvents are used, the cost is too high, and the residual amount of solvents in the product is large, which has a great impact on product quality and serious environmental pollution.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Add 20g of atorvastatin calcium containing 30% crystal form V, 50% crystal form VII, 10% crystal form XI and other unknown crystal forms to 60 ml of 95% (volume ratio) ethanol aqueous solution, and heat and stir to dissolve After the hot filtration, the filtrate is kept warm so that atorvastatin calcium does not precipitate. Turn on the carrier gas nitrogen and spray dryer to heat and recover the solvent cold trap device, preheat for about 10-20 minutes, make the inlet air temperature 75 ℃, cold trap The temperature is 6℃, the oxygen content in the spray drying system drops to a safe range, turn on the peristaltic pump, rotate at 15-25rpm, start spray drying, adjust the speed of the peristaltic pump so that the outlet air temperature is maintained at 55-60℃, and dry it well. The material is obtained by bagging, and the product is 18.6 g, the yield is 93%, and the amorphous form accounts for 99.1% by crystal form determination.

Embodiment 2

[0017] Add 20 g of atorvastatin calcium with an unknown crystal form ratio to 60 ml of 95% (volume ratio) ethanol aqueous solution, heat and stir to dissolve, heat the filtrate after hot filtration to keep the atorvastatin calcium from precipitating, turn on the carrier gas nitrogen and Spray dryer heating and solvent recovery cold trap device, preheating for about 10-20 minutes, so that the inlet air temperature is 110 ℃, the cold trap temperature is 6 ℃, the oxygen content in the spray drying system is reduced to a safe range, and the peristaltic pump is turned on , The speed is 15-25rpm, start spray drying, adjust the speed of the peristaltic pump to keep the outlet air temperature at 75-85℃, and bag the dried materials to get 18.7g of product, yield 93.5%, determined by crystal form Amorphous form accounted for 99.1%.

Embodiment 3

[0019] Add 20g of atorvastatin calcium with unknown crystal form ratio to 60ml of 95% (volume ratio) methanol aqueous solution, heat and stir to dissolve, heat the filtrate after hot filtration to keep the atorvastatin calcium from precipitating, turn on the carrier gas nitrogen and Spray dryer heating and solvent recovery cold trap device, preheating for about 10-20 minutes, so that the inlet air temperature is 110 ℃, the cold trap temperature is 6 ℃, the oxygen content in the spray drying system is reduced to a safe range, and the peristaltic pump is turned on , The speed is 15-25rpm, start spray drying, adjust the speed of the peristaltic pump to keep the outlet air temperature at 75-85℃, and bag the dried materials to get 18.7g of product, yield 93.5%, determined by crystal form Amorphous form accounted for 99.2%.

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PUM

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Abstract

The invention discloses a method for preparing amorphous Atorvastatin calcium. The current method uses more solvent, so the cost is over high; and the residual quantity of the solvent in a product is large, thereby causing big influence on the quality of the product and causing serious environmental pollution. In the method, alcohol solvent and water are combined into mixed alcohol-water solvent which dissolves Atorvastatin calcium containing one or more crystal forms completely; proper temperature is kept for ensuring that the Atorvastatin calcium is not precipitated; and the amorphous Atorvastatin calcium is precipitated by a spray drying method. The method uses the mixed alcohol-water solvent which is removed from the product easily, has little organic residue and causes less influence on drug quality; the usage amount of the solvent is reduced greatly; the concentration of the Atorvastatin calcium in the solution is high; and the purity of the prepared product of the amorphous Atorvastatin calcium is high.

Description

Technical field [0001] The invention discloses a preparation method of amorphous atorvastatin calcium. Background technique [0002] The chemical name of Atorvastatin is [R-(R,R)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3 -Phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid. Atorvastatin hemicalcium salt can be effectively used as a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, so it can be used as a hypolipidemic and cholesterol-lowering drug. [0003] Some existing patents or patent applications have reported some methods for preparing amorphous atorvastatin calcium: U.S. Patent 6,528,660 and 6,613,916; U.S. Patent Application Publication 2002 / 183378, 2003 / 109569, 2006 / 0106230; and International ( PCT) patent applications WO 01 / 2899, WO02 / 57288, WO 02 / 83637, WO 02 / 83638, WO 03 / 18547, WO 03 / 68739, WO03 / 078379 and WO 2006045018 and so on. [0004] Some of the above-mentioned documents mention the use of spray drying to prepare ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/34
Inventor 金志平金远方谢作念王法平
Owner ZHEJIANG JINGXIN PHARMA
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