3-in-1 Conical Vacuum Dryer & Mixing Reactor for Cefodizime sodium Introduction
Cefodizime sodium is the world's first third-generation cephalosporin with immune-enhancing function. Cefodizime sodium has a broad antibacterial spectrum and can enhance the immune function of the human body. Whiteneria, Proteus vulgaris, Neisseria gonorrhoeae, Salmonella, Meningococcus, Escherichia coli, Haemophilus influenzae and Corynebacterium all have good inhibitory effects. However, cefodizime acid is used as a key intermediate for the synthesis of cefodizime sodium. In the prior art, the purity of cefodizime acid products sold in the market is not high enough, and the purity of its downstream product cefodizime sodium is certain. It is unable to meet the needs of manufacturers producing cefodizime sodium. Therefore, it is necessary to conduct further research on its purification method.
The preparation method of high-purity cephalosporin-based raw material medicine cefodizime sodium generally adopts a solvent process, and the specific steps are:
(1) Dissolve sodium isooctanoate in ethanol solution to obtain an ethanol solution of sodium isooctanoate;
(2) Add ethanol, cefodizime acid and triethylamine at 0～30℃, mix and stir to clear, decolorize, and obtain cefodizime acid solution;
(3) Mix the above-mentioned isotropic sodium ethanol solution and cefodizime acid solution to precipitate a solid of cefodizime sodium.
(4) Wash the filter cake with absolute ethanol and acetone, filter with suction to obtain the wet material of cefodizime sodium; filter and dry.
However, in the long-term production practice, it has been found that the prepared cefodizime sodium has the following shortcomings: relatively small particles, powdery; high static electricity, poor fluidity, difficulty in dispensing when making reagents, and large residual ethanol. The process still needs further improvement.
New refining process for high-purity cephalosporin raw material medicine cefodizime sodium
Compared with other existing technical solutions, the new refining process of the high-purity cephalosporin raw material medicine cefodizime sodium has the advantages of simple operation, high yield and high product purity. The product prepared by the new process has the following advantages: uniform particle size of cefodizime sodium, good fluidity, and easy dispensing; low solvent residue, ethanol residue below 0.3%, and solvent residue reduced by 90.0%. The specific process steps are:
(1) First, dissolve sodium isooctanoate in an ethanol solution, add a small amount of hydrochloric acid, until the pH of the solution is 6.0-6.5, to obtain an ethanol solution of sodium isooctanoate;
(2) At room temperature, sequentially mix ethanol, cefodizime acid, benzophenone hydrazone, sodium metabisulfite, and triethylamine, and stir until cefodizime acid is dissolved to obtain a cefodizime acid solution. Use activated carbon for injection to decolorize the cefodizime acid solution at 0-30°C.
(3) Decolor the cefodizime acid solution obtained in step 2, and then mix the decolorized cefodizime acid solution with the ethanol solution of sodium isooctanoate obtained in step 1, stirring, and add a small amount of hydrochloric acid until the pH of the solution is 6.5~ 7.0 to obtain an ethanol solution of cefodizime sodium crystals;
(4) Purify the crystals of cefodizime sodium in a sterile filter washing dryer using ethanol solvent. Wash the filter cake with absolute ethanol for 15-20 minutes, filter with suction, then wash the filter cake with acetone for 15-20 minutes, and filter with suction to obtain a wet cefodizime sodium;
(5) Dry the wet material of cefodizime sodium with a sterile filter washing dryer. Vacuum drying in a three-in-one dryer for 1 hour, followed by drying with hot water at 50-53°C for 6-8 hours, to obtain a finished product of cefodizime sodium with a water content of less than 3.5% by weight.
3-in-1 Conical Vacuum Dryer & Mixing Reactor for Cefodizime sodium Working Process Improvement
(1) The design and assembly of the equipment are carried out in strict accordance with the national GMP and US FDA requirements, fully comply with the requirements of the pharmaceutical production process, and the system is safe, stable and reliable;
(2) Equipment materials are strictly controlled. The parts in direct contact with the material are made of non-toxic, corrosion-resistant SUS316L material, PTFE or EPDM sealing material. The filter screen adopts SUS316L metal sintered screen to avoid fiber generation;
(3) The inner surface of the equipment directly in contact with the material is flat, smooth, without dead ends, and is easy to clean and disinfect;
(4) The equipment does not pollute the environment outside the device, and measures such as dust prevention, leak prevention, heat insulation, and noise prevention are properly taken. The fully enclosed working state, the motor, reducer, and lifting device are protected by stainless steel outer covers, and the jacket return channel is insulated with thermal insulation felt, which greatly reduces heat loss and influence on the outside world;
(5) Strictly use safe and reliable explosion-proof electrical appliances, and equipped with pulleys to eliminate static electricity and other safety interlocking functions and safety devices.
(6) All pipelines for materials, solvents, nitrogen, etc. are designed with no dead ends or blind pipes. The surface of the equipment is automatically polished or spot-polished by mechanical automatic polishing. The inner surface of the equipment is Ra≤0.4 and the outer surface is Ra≤0.8;
(7) The stirring shaft and side discharge valve stem are protected by metal bellows;
(8) Removable rotating cleaning spray ball for online cleaning;
(9) Dry-method double-end mechanical seal, nitrogen protection and cooling, and online leak detection.
(10) The dust trap can be CIP, and the rotary joint can be used for online leak detection.
Compared with other existing technical solutions, 3-in-1 Conical Vacuum Dryer & Mixing Reactor for Cefodizime sodium has the advantages of simple operation, high yield, and high product purity. The product prepared by the aseptic filter washing dryer has the following advantages: uniform particle size of cefodizime sodium, good fluidity, easy dispensing; low solvent residue, ethanol residue below 0.3%, and solvent residue reduced by 90.0%.
Keyword:Cefodizime sodium dryer, cephalosporin antibacterial drug purification equipment, high-purity antibiotic filtration washing and drying three-in-one, cephalosporin API refining equipment, sterile filter washing dryer