Device and method for improving stability of crystals by using continuous and rapid reactive crystallization

A fast-reacting and stable technology, applied in solution crystallization, chemical instruments and methods, chemical/physical/physical-chemical stationary reactors, etc., can solve the problem of uneven crystal particle size distribution, unguaranteed residence time, different residence time and other problems, to achieve the effect of good purity and stability, saving resources and labor, and reducing consumption time

Active Publication Date: 2014-02-05
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This unequal residence time of reactants and products, in addition to reducing yields, can lead to non-uniform crystal size distribution
For some drugs that degrade during the reaction, in extreme cases, different residence times may lead to substantial degradation of the product during production
[0008] Third, intermittent operations require regular downtime
For example, the reaction process and the crystallization process still occur simultaneously in the same container, and a uniform residence time cannot be guaranteed.

Method used

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  • Device and method for improving stability of crystals by using continuous and rapid reactive crystallization
  • Device and method for improving stability of crystals by using continuous and rapid reactive crystallization
  • Device and method for improving stability of crystals by using continuous and rapid reactive crystallization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] A device for continuous rapid reaction crystallization to improve crystal stability, such as figure 1 , 2 , 3, including a tank reactor 4 and a tubular reactor 5 connected in series; a liquid jet impact feed device 6 is set in the tank reactor 4, and the liquid jet impact feed device 6 includes a vertical Straight hollow tube 601 and two feeding tubes 602, the tube wall of hollow tube 601 is provided with through hole 603 for feeding tube to pass, and described feeding tube 602 is inserted from the upper port of hollow tube 601, and from The through hole 603 on the pipe wall passes through, and the discharge port of the feeding pipe 602 is connected with a nozzle 605, and the nozzle 605 of each feeding pipe is fixed by a fixing frame 604, and the fixing frame is uniformly arranged along the circumference of the pipe. There are two clamping holes 607 for fixing the nozzle; the feeding pipe section between the through hole 603 on the hollow pipe and the fixing frame 604 ...

Embodiment 2

[0054] The difference between the continuous rapid reaction crystallization of the present implementation and the device for improving crystal stability is that the liquid jet impacts the feeding device, wherein the angle formed between the nozzle and the horizontal plane is 10°, and the distance is 12mm, such as image 3 (d) shown.

[0055] Production process of continuous rapid reaction crystallization of cefuroxime sodium in a pilot-scale reactor

[0056] Dissolve 720g of sodium lactate (60%) in a mixed solvent of 3200ml of acetone and 4000ml of ethanol (95%) at 20-25°C. After stirring for 20 minutes, the mixture was filtered, washed with 1000 ml of ethanol (95%), and put into a beaker together with the filtrate (the first feed liquid 1). Dissolve 800g of cefuroxime acid in a mixed solvent of 2000ml of acetone and 1000ml of ethanol (95%), add 100g of activated carbon and stir at 38-42°C for 20-30 minutes to decolorize. Then, the mixture was filtered, and the activated car...

Embodiment 3

[0063] The continuous rapid reaction crystallization of this implementation improves the device of crystal stability and the difference of embodiment 1 is:

[0064] The angle between the nozzle and the horizontal plane is 15°, and the spacing is 10mm, such as image 3 (e) shown.

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Abstract

The invention discloses a device and method for improving stability of crystals by using continuous and rapid reactive crystallization. The device comprises a kettle-type reactor and a tubular reactor connected with the kettle-type reactor in series, wherein the kettle-type reactor is internally provided with a liquid jet impacting feeding device; the liquid jet impacting feeding device comprises a hollow pipe and more than two feeding pipes, and the pipe wall of the hollow pipe is provided with a through hole through which the feeding pipes pass; the feeding pipes are inserted from an upper port of the hollow pipe and can go out from the through hole in the pipe wall, discharge openings of the feeding pipes are connected with nozzles, and the discharge opening and/or nozzle of each feeding pipe is fixed at the lower end part of the hollow pipe through a fixing frame; the nozzles are arranged in a specific way to ensure compacting collision, and a feeding pipe section between the through hole in the hollow pipe and the fixing frame is of an arc-shaped structure. The device and the method provided by the invention have the advantages that the average size and granularity of the crystals are uniform, and the purity and stability of a product are greatly improved.

Description

technical field [0001] The invention belongs to the technical field of chemical and pharmaceutical crystallization, and in particular relates to a device and method for continuous rapid reaction crystallization to improve crystal stability. Background technique [0002] The crystallization process, as an important basic production process, is widely used in various industrial fields. Therefore, the quality of the crystals produced has a significant impact on downstream processes such as filtration, grinding and drying, as well as transport and storage. [0003] Stability is an important consideration for many pharmaceutical crystalline compounds. It is well known that most of the crystalline pharmaceutical compounds obtained through the reaction crystallization process contain both crystalline and amorphous structures. Crystal structure, because of its lower internal free energy can make the drug more stable. Changes in a drug's crystalline form can not only affect its ap...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J19/18B01J19/00B01D9/02C07D501/34C07D501/04C07D501/12
Inventor 王学重刘文菁刘晶晶
Owner SOUTH CHINA UNIV OF TECH
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