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Preparation method of ziprasidone or its salt inclusion

A technology for ziprasidone and clathrates, which is applied in the field of preparation of ziprasidone mesylate clathrates, can solve problems such as hydrolysis, efficiency reduction, and water deterioration, and achieve low cost, high efficiency, and time-consuming short effect

Inactive Publication Date: 2006-10-04
SHANGHAI INST OF PHARMA IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inclusion time of this method is as long as 4 days, and such a long preparation time obviously reduces the efficiency, especially in large-scale production, it is difficult to achieve a practical effect for such a long time; ziprasidone is very unstable in aqueous solution, In the preparation process, water is used as the medium and a long inclusion time is added, which will cause hydrolysis of the drug before it is completely included; water is used as the medium and a long inclusion time is also easy to cause bacterial contamination, resulting in water deterioration. Does not meet the requirements of GMP
[0004] In the prior art, ziprasidone or its salt is put into an organic solvent containing cyclodextrin and its derivatives, and heated to reflux at 80°C for 2 hours to obtain an inclusion compound, but ziprasidone or its salt is easily oxidized , at 80°C, the color of the clathrate will be darkened due to oxidation, resulting in impurity of the product

Method used

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Examples

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preparation example Construction

[0038] The preparation method of the present invention is to add ziprasidone or its salt raw material, cyclodextrin and its derivatives into the solvent, heat and reflux at 78±1.0°C until the drug is completely dissolved; evaporate the solvent to obtain ziprasidone Water-soluble clathrates of ketones or their salts.

[0039] The ratio of the drug to the cyclodextrin affects the quality of the clathrate, and the molar ratio of the drug to the cyclodextrin in the present invention is 1.87±1.5:1, preferably 1.87:1.

[0040] The solvent used in the present invention is selected from: (i) ethanol (boiling point is 78.3 ℃); (ii) mixed solvents of ethanol and other solvents (such as acetonitrile, acetone, isopropanol (82.3 ℃), tetrahydrofuran); (iii) ethanol A mixed solvent with water; (iv) a mixed solvent consisting of (ii) and (iii). An aqueous ethanol solution is preferred, wherein the volume percentage of ethanol is 90-100%, preferably 95-100%, more preferably 99-100%.

[0041]...

Embodiment 1

[0062] Preparation of clathrate

[0063] Add 25.09 grams of ziprasidone mesylate hemihydrate and 752.7 grams of HPBCD to 4 liters of absolute ethanol, heat and reflux in a water bath at 78°C for 2 hours to fully dissolve and filter, and concentrate under reduced pressure to constant weight to obtain Drug-HPBCD inclusion complex. Add water to dissolve the above-mentioned clathrate, add water to 3 liters, filter through a 0.2-micron microporous membrane, pack in a can, and freeze-dry to obtain ziprasidone mesylate for injection.

[0064] The results showed that the clathrate obtained was white in color and high in purity (>99.7%).

Embodiment 2-4

[0067] Add 25.09 grams of ziprasidone mesylate hemihydrate and 752.7 grams of HPBCD with different contents in the above table to 4 liters, heat and reflux in a water bath at the temperature listed above for 2 hours to fully dissolve, Concentrate under reduced pressure to constant weight to obtain drug-HPBCD inclusion complex. Dissolve the clathrate with water, add water to 3 liters, filter through a 0.2-micron microporous membrane, pack in a can, and freeze-dry to obtain ziprasidone mesylate for injection.

[0068] result

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Abstract

The invention relates to a process for preparing Ziprasidone or its salt inclusion compound, which comprises the steps of, (1) providing a solution of Ziprasidone or its salts, heating the solution at 78+-1.5 deg C to dissolve Ziprasidone or its salts, (2) filtering non-soluble substance in the solution, then drying the dissolvent.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a preparation method of ziprasidone mesylate inclusion compound. Background technique [0002] Inclusion technology is a commonly used method in the field of modern pharmacy. It can use cyclodextrin and its derivatives as carriers to encapsulate insoluble drugs in the internal space of its molecular helical structure through different methods. This clathrate can significantly improve the water solubility of the drug and can be made into various dosage forms. [0003] In inclusion technology, different inclusion methods will bring different results to the solubility and stability of inclusion compounds. The water solubility of ziprasidone is very low and inclusion technique must be used. In the prior art, hydroxypropyl-beta-cyclodextrin (HPBCD) or thiobutyl ether-beta-cyclodextrin (SBECD) is made into a 40% aqueous solution, and ziprasidone mesylate is added, at room ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/496A61K9/08A61K9/02A61K9/14A61K9/16A61K9/20A61K9/48A61K47/40A61P25/00
Inventor 瞿文包泳初陈庆华朱宝泉
Owner SHANGHAI INST OF PHARMA IND
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