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New crystal form of (R)-Lansoprazole sodium and preparation method thereof

A technology of dexlansoprazole sodium and lansoprazole sodium, which is applied in the field of drug preparation, can solve the problems of low stability of preparation products, poor stability of dexlansoprazole, sensitivity to temperature and humidity, etc., so as to avoid sulfoxide The effect of structural oxidation, good crystal morphology, and moderate crystal size

Active Publication Date: 2017-05-31
NANJING HERON PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] In view of the poor stability of dexlansoprazole in the prior art, it is sensitive to temperature and humidity, it is difficult to operate in the preparation process, the production cost is high, and the defects of its preparation product stability are not high, especially some are not suitable for hot melt extrusion Due to the defects of the process, such as obvious drug degradation in the hot-melt process, the invention provides a new crystal form A of dexlansoprazole sodium dimethylacetamide solvate and a preparation method thereof, the new crystal form A Better physical and chemical properties, suitable melting point, strong stability, very convenient to be made into various pharmaceutical dosage forms, and also convenient to be processed by hot-melt extrusion process

Method used

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  • New crystal form of (R)-Lansoprazole sodium and preparation method thereof
  • New crystal form of (R)-Lansoprazole sodium and preparation method thereof
  • New crystal form of (R)-Lansoprazole sodium and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Embodiment 1 Preparation of new crystal form A of dexlansoprazole sodium

[0049] Add 50 g of dexlansoprazole sodium into a mixed solvent of 200 mL of dimethylacetamide and 100 mL of purified water, add 0.1 g of copovidone S630, and 0.1 g of propyl gallate, stir and dissolve at 35°C to 40°C, Under the condition of applying ultrasonic wave, the frequency of ultrasonic wave is 20KHz~50KHz, the power is 50W~100W, slowly add 900mL of methyl tert-butyl ether into the above solution, and maintain the cooling rate at 0.3~1℃ / min Under certain conditions, lower the temperature to 0-5°C, continue to stir for 1-3 hours, filter the formed suspension to dryness, and dry it at a temperature of 35-45°C and a vacuum of 0-0.1Mpa to obtain dexlansola The new crystal form A of azole sodium dimethylacetamide solvate is about 57g, and the yield is 93%.

Embodiment 2

[0050] Embodiment 2 Preparation of new crystal form A of dexlansoprazole sodium

[0051] Add 50g of dexlansoprazole sodium into a mixed solvent of 200mL of dimethylacetamide and 200mL of purified water, add 0.1g of PEG4000, and 0.1g of cysteine ​​hydrochloride, stir and dissolve at 35-40°C, and apply Under the condition of ultrasonic action, the frequency of ultrasonic action is 20 KHz ~ 50KHz, the power is 50 W ~ 100W, slowly add 1600mL of methyl isobutyl ether to the above solution, and maintain the cooling rate at 0.3 ~ 1°C / min. , lower the temperature to 0-5°C, continue to stir for 1-3h, filter the formed suspension to dryness, and dry it at a temperature of 35-45°C and a vacuum of 0-0.1Mpa to obtain dexlansoprazole sodium The new crystal form A of dimethylacetamide solvate is about 54g, and the yield is 88%.

Embodiment 3

[0052] Embodiment 3 Preparation of new crystal form A of dexlansoprazole sodium

[0053] Add 50g of dexlansoprazole sodium into a mixed solvent of 200mL of dimethylacetamide and 100mL of purified water, add 0.1g of povidone K30, and 0.1g of butylhydroxyanisole, stir and dissolve at 35-40°C, Under the condition of applying ultrasonic waves, the frequency of ultrasonic waves is 20-50KHz, and the power is 50-100W. Slowly add 900mL of isopropyl ether to the above solution, and keep the cooling rate at 0.3-1°C / min. 0~5℃, continue to stir for 1~3h, suction filter and dry the formed suspension, and dry under the conditions of temperature 35~45℃ and vacuum degree 0~0.1Mpa to obtain dexlansoprazole sodium dimethyl The new crystal form A of acetamide solvate is about 55g, and the yield is 89%.

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Abstract

The invention discloses a new crystal form A of a (R)-Lansoprazole sodium dimethylacetamide solvate and a preparation method thereof. The powder X-ray diffraction spectrum has the feature diffraction peak in the position where the diffraction angle 2Theta is 5.9, 7.6, 12.2, 12.7, 16.6, 18.4, 20.5, 25.8, 26.8 and 31.4 degrees. The preparation method for the new crystal form A comprises the following steps: adding the (R)-Lansoprazole sodium to a mixed solvent of the dimethylacetamide and water, adding the suitable amount of a viscosity modifier and an antioxidant, adding a poor solvent after dissolving and clarifying, and slowly crystallizing to obtain the new crystal form A. The new crystal form A of the (R)-Lansoprazole sodium dimethylacetamide solvate has the advantages of moderate crystal granularity, good mobility, difficult aggregation and degradation, and good stability, and is suitable for the hot-melting extrusion process. The preparation process of the new crystal form A is simple, the cost is low, the yield is high, the solvent is safe and non-toxic, and the new crystal form A is suitable for the industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and relates to a new crystal form A of dexlansoprazole sodium dimethylacetamide solvate and a preparation method thereof. Background technique [0002] Dexlansoprazole (Dexlansoprazole, R-(+)-Lansoprazole), the chemical name is (R)-(+)-2-([3-methyl-4-(2,2,2-trifluoroethoxy Base) pyridin-2-yl] methylsulfinyl) -1H-benzimidazole, its structural formula is as follows, [0003] . [0004] Dexlansoprazole is a new drug for the treatment of esophagitis developed by Japan's Takeda Pharmaceutical Company, which was approved for listing by the U.S. FDA on January 30, 2009. The drug is a single enantiomer of the proton pump inhibitor lansoprazole, used for the treatment of heartburn and varying degrees of erosive esophagitis associated with non-erosive gastroesophageal reflux disease, and has a higher activity than lansoprazole Bioavailability and fewer side effects. [0005] The physical...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12A61K31/4439A61P1/04A61P31/04
CPCC07B2200/07C07B2200/13C07D401/12
Inventor 胡永康闵涛郭彦飞郭梦玲柏丹丹叶海周桂梅刘飞
Owner NANJING HERON PHARM CO LTD
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