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Pantoprazole sodium compound monohydrate sphaerocrystal and preparation method thereof

A technology for pantoprazole sodium and monohydrate, which is applied in the field of pantoprazole sodium compound monohydrate spherical crystal and preparation thereof, can solve the problems of poor thermal stability, fluctuating product quality, low bulk density and the like, Achieve the effects of good water solubility, high dissolution rate and uniform particle size distribution

Active Publication Date: 2015-12-02
TIANJIN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the crystalline form of these pantoprazole sodiums that patent has reported mostly is the form of sheet-like solvate, generally exists the poor fluidity and thermal stability problem, and this just may cause the fluctuation of product quality
At present, the pantoprazole sodium products used in the domestic market are mainly pantoprazole sodium monohydrate, which also has problems such as small particle size, low bulk density, and poor fluidity.

Method used

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  • Pantoprazole sodium compound monohydrate sphaerocrystal and preparation method thereof
  • Pantoprazole sodium compound monohydrate sphaerocrystal and preparation method thereof
  • Pantoprazole sodium compound monohydrate sphaerocrystal and preparation method thereof

Examples

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Effect test

Embodiment 1

[0024] Add 8 g of dried pantoprazole sodium solids to 40 mL of a mixed solvent of n-propanol and isopropanol at 40°C to dissolve, wherein the volume ratio of n-propanol to isopropanol is 1:1; stir the above solution at 150 rpm Lower the temperature at a rate of 0.2°C / min, and when the temperature drops to 10°C, add 0.4ml of dichloromethane dropwise as a bridging agent, grow crystals at a constant temperature for 30 minutes, and then cool down to 0 at a rate of 0.2°C / min while stirring at 150rpm. ℃, continue stirring at 150rpm for 30min, vacuum filter the slurry, and dry the filter cake at 50℃ under normal pressure for 48h to constant weight to obtain spherical crystals of pantoprazole sodium monohydrate. The purity of the product obtained by the method is 99.1%, and the single-pass molar yield of the crystallization process is 92.3%. The X-ray powder diffraction pattern of the product is as figure 1 As shown, the thermal analysis diagram of the product is shown in figure 2 ...

Embodiment 2

[0026] Add 14 g of the dried pantoprazole sodium solid into 50 mL of n-butanol at 45°C to dissolve; lower the temperature of the above solution at a rate of 0.5°C / min under stirring at 180 rpm, and when the temperature drops to 15°C, add 1 mL dropwise chloroform at constant temperature for 40 minutes, then cooled to 2°C at a rate of 0.5°C / min under stirring at 180rpm, continued to stir at 180rpm for 60 minutes, vacuum filtered the crystal slurry, and dried the filter cake at 50°C and normal pressure for 40h to constant temperature. Weight, to obtain pantoprazole sodium monohydrate spherical crystals. The purity of the product obtained by the method is 99.3%, and the single-pass molar yield of the crystallization process is 91.0%. The obtained spherical crystals have a uniform particle size distribution, the coefficient of variation C.V.=0.30, the average particle size is equal to 156 μm, and the bulk density is 0.50 g / cm 3 , the compressibility factor is 15%, and the angle of...

Embodiment 3

[0028] Add 13 g of dry pantoprazole sodium solids to 45 mL of n-propanol and sec-butanol mixed solvent at 45°C for dissolution, wherein the volume ratio of n-propanol and sec-butanol is 1:3; Cool down at a rate of 0.8°C / min under stirring, and keep the temperature down to 20°C, drop 1mL of isopropyl acetate as a bridging agent, grow crystals at a constant temperature for 50min, and then cool down at a rate of 0.8°C / min under stirring at 160rpm to Continue stirring at 160 rpm for 70 min at 2°C, vacuum filter the crystal slurry, and dry the filter cake at 55°C under normal pressure for 35 hours to constant weight to obtain spherical crystals of pantoprazole sodium monohydrate. The purity of the product obtained by the method is 99.5%, and the single-pass molar yield of the crystallization process is 91.1%. The obtained spherical crystals have a uniform particle size distribution, the coefficient of variation C.V.=0.29, the average particle size is equal to 153 μm, and the bulk d...

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Abstract

The invention relates to a pantoprazole sodium compound monohydrate sphaerocrystal and a preparation method thereof. The average particle size of the crystal is greater than 150 mu m, the coefficient of variation (C.V.) value is less than 0.32, and the bulk density is greater than 0.45 g / ml. The preparation method comprises the following steps: adding a pantoprazole sodium solid into a solvent to prepare a 0.2-0.3 g / ml solution at 40-50 DEG C; cooling the solution under stirring actions, keeping the temperature constant when the temperature drops to 10-25 DEG C, adding a bridging agent, and growing the crystal at constant temperature for 30-60 minutes; continuing cooling to 0-5 DEG C at the same stirring rate, and continuing stirring at the same stirring rate for 30-90 minutes; and carrying out vacuum filtration on the formed crystal slurry, and drying the filter cake at 50-60 DEG C to constant weight, thereby obtaining the pantoprazole sodium monohydrate sphaerocrystal. The method can directly perform tabletting, and is simple and controllable in operating conditions. The single-pass mole yield of the crystallization process is 90% or above, and the product purity is 99% or above.

Description

technical field [0001] The invention belongs to the technical field of medicine separation, in particular to a pantoprazole sodium compound monohydrate spherical crystal and a preparation method thereof. Background technique [0002] Pantoprazole sodium (Pantoprazolesodium) is a white or off-white crystalline powder, easily soluble in water or methanol, almost insoluble in chloroform or ether. The chemical name of pantoprazole sodium is 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl-1H-benzimidazole sodium salt, Molecular formula is C 16 h 14 f 2 N 3 NaO 4 S, molecular weight is 405.36, structural formula such as formula (I). As a proton pump inhibitor, pantoprazole sodium is suitable for the treatment of acute upper gastrointestinal bleeding such as duodenal ulcer, gastric ulcer, acute gastric mucosal lesions, and complex gastric ulcer. The cell's proton pump (ie, H+ / K+-ATPase) binds and inhibits gastric acid secretion. [0003] [0004] Pantoprazo...

Claims

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Application Information

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IPC IPC(8): C07D401/12A61K31/4439A61K9/48A61P1/04
CPCC07B2200/13C07D401/12
Inventor 郝红勋陶灵刚闫佳琦王永莉吕军尹秋响侯宝红徐昭姜琛谢闯
Owner TIANJIN UNIV
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