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A kind of particle size control method of cefdinir

A cefdinir and particle size control technology, which is applied in the field of pharmaceutical and chemical technology synthesis, can solve the problems of large particle size, difficult dissolution, and difficulty in granulation of preparations, etc.

Active Publication Date: 2021-04-27
苏州盛达药业有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] CN106279207A discloses the preparation method of cefdinir, but, because cefdinir is insoluble in water, therefore in the process of adjusting pH value, the crystallization of cefdinir is not easy to control, often its particle size key index D 90 More than 100um, such a large particle size is not easy to dissolve after being made into a preparation, and at the same time, it is not easy to granulate the preparation if the particle size is too large

Method used

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  • A kind of particle size control method of cefdinir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The synthesis method is specifically:

[0027] (1) In a 1000mL flask, add 45.2g 7-AVCA, 96g cefdinir active ester, 300ml THF, control the temperature at 10-15°C, slowly add THF and TEA mixture (40mlTHF, 43mlTEA) dropwise. After the dropwise addition is completed, control the temperature at 10-20°C and keep the temperature for reaction. Samples were taken to measure the residue of 7-AVCA. After the end point is qualified, add 300ml MTC, 100ml H 2 O, extraction, layering. 10 wt% K for the aqueous phase 2 CO 3 Hydrolyze for 20 minutes, adjust the pH to 4.2-4.4 with 2N HCL, and grow crystals for half an hour. Adjust the pH value to 2.2-2.4, cool down 10-15°C, filter, H 2 Rinse with O, wash with ethanol, and dry under vacuum at 45° C. to obtain about 72 g of cefdinir with a yield of 90.5%.

[0028] (2) 500ml acetonitrile is cooled to 5 ℃~10 ℃, add the phosphoric acid solution of 80g 85wt%, add cefdinir, heat preservation reaction 2 hours, suction filtration, acetonitr...

Embodiment 2

[0030] Embodiment 2 Get 72g cefdinir crude product,

[0031] The synthesis method is specifically:

[0032] (1) Cool 500ml of acetonitrile to 5°C-10°C, add 80g of concentrated sulfuric acid, add 72g of cefdinir prepared in step (1) of Example 1, take 10min-15min, keep warm for 2 hours, filter with suction, and wash with ECN , dried in vacuum at 45°C to obtain about 88 g of cefdinir sulfate.

[0033] (2) At 0-5°C, 600ml H 2 Add cefdinir sulfate and 6wt% ammonia solution in O, until dissolving clear, add 5g active carbon decolouring 45 minutes after dissolving clear. Suction filtration, 100ml H 2 Wash the carbon with O, add 40mL of acetone, control the solution temperature at 25-28°C, adjust the pH to 4.2-4.4 with 2N HCL, stir rapidly, and grow the crystal for half an hour. Then lower the current pH value by 0.25 every 5 minutes, adjust the pH value in a gradient until the pH value is adjusted to 2.2-2.4, grow the crystal for another hour, filter, H 2 0, ethanol washing, 45...

Embodiment 3

[0035] The synthesis method is specifically:

[0036] At 0~5℃, 600ml H 2 Add cefdinir and sodium bicarbonate that 72g embodiment 1 step (1) makes in O, add 5g active carbon decolouring 45 minutes after dissolving clear. Suction filtration, 100ml H 2 Wash the carbon with O, add 20mL of methanol and 20mL of acetone, control the temperature of the solution at 25-28°C, adjust the pH to 4.2-4.4 with 2N hydrochloric acid, stir rapidly, and grow the crystal for half an hour. Then lower the current pH value by 0.2 every 5 minutes, adjust the pH value in a gradient until the pH value is adjusted to 2.2-2.4, grow the crystal for another hour, filter, H 2 0, ethanol washing, 45 ℃ of vacuum dryings get cefdinir finished product 65g, yield 90%, record particle size D 90 It is 45um.

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Abstract

The invention relates to a method for controlling the particle size of cefdinir. The crude product of cefdinir or the finished product of cefdinir or the compound salt of cefdinir is dissolved in alkali at 0-25°C in the presence of water to obtain a mixed solution; the temperature is controlled At 20-35°C, use acid to adjust the pH of the mixed solution to 3.9-4.5, grow crystals for 0.5-1 hour, then adjust the pH value to 2.2-2.6 with a gradient, and control the temperature at 5-35°C to continue growing Crystallize for 0.5~1.5 hours; then filter, wash, and dry to obtain cefdinir with the required particle size. The present invention can obtain cefdinir particle size key index D as required 90 In the range of 30-100um, to meet the particle size requirements of different dosage forms of cefdinir, particle size data under different conditions measured by a particle size analyzer show different size ranges and are all normal distributions, and the crystallization and recrystallization yields of the present invention more than 90 percent.

Description

technical field [0001] The invention belongs to the technical synthesis field of medicine and chemical industry, and in particular relates to a method for controlling the particle size of cefdinir. Background technique [0002] Cefdinir was developed by Fujisawa Pharmaceutical Co., Ltd., Japan. The third-generation oral broad-spectrum cephalosporin antibiotics launched in October 1991. It has a wide antibacterial spectrum and few side effects, and is clinically suitable for oral use by the elderly and children. After cefdinir was launched in China, different companies developed different oral dosage forms according to different market demands. At present, there are mainly dosage forms such as dispersible tablets, granules, and capsules on the market. Different dosage forms have different particle size requirements for cefdinir, so as to ensure that different dosage forms meet their corresponding dissolution rate or bioavailability requirements. [0003] CN106279207A discl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/22C07D501/12
CPCC07D501/12C07D501/22
Inventor 周自金黄军豪陈锋罗新祖温雄飞彭尧青孙悦铭
Owner 苏州盛达药业有限公司