Development and application of oxazolidinone-type sterile plate-type filtration, washing and drying three-in-one equipment for separation and purification of antibiotic raw materials
Linezolid is an oxazolidinone antibiotic approved by the US FDA in 2000 for the treatment of bacteremia caused by vancomycin-resistant enterococci (VER), pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) and Treatment of combined skin infections and bacteremia caused by penicillin-resistant Streptococcus pneumoniae (PRSP).
One of the difficulties in the preparation of linezolid is the construction of the five-membered ring of oxazolone in its structure. The existing preparation process has the following problems:
(1) Using a high-boiling-point alcohol solvent process, the energy consumption required to evaporate this type of solvent is huge and the evaporation rate is slow, the prepared crystal form has agglomeration, and the appearance and purity are poor;
(2) The high-temperature suspension crystallization method in water is adopted. Since the solubility of linezolid in water varies greatly with temperature, the solubility is higher at high temperature and lower at low temperature, and a more stable crystal form will be precipitated during the cooling process. Crystal form I transforms into crystal form II relatively quickly at a low temperature, and the process for preparing linezolid crystal form I using this method is unstable, and the crystal form purity is not high.
In the field of linezolid, there is an urgent need for a method for preparing linezolid crystal form I with high purity and stable crystal form, which is easy to operate.
Compared with the existing technical methods, the three-in-one flat-plate filtration, washing and drying of oxazolidinone antibiotic raw materials has the advantages of easy access to reagents, mild reaction conditions, environmental friendliness, high yield and purity, and the like.
Three-in-one process flow of oxazolidinone sterile flat plate filter washing and drying
(1) Impurity removal of crude linezolid
In the three-in-one plate filter, washing and drying system, the crude linezolid is mixed with a specific solvent, filtered, and the filtrate is collected; after the crude linezolid is mixed with the solvent, stir at 85-105°C until the crude product dissolves, and then filter while hot , collect the filtrate.
(2) Crystallization of linezolid solvent after purification
Add the second solvent to the filtrate obtained in step (1), add the linezolid crystal form I seed, and carry out the crystallization process at 85-105°C; 2) Growing crystals at low temperature for 5-30 minutes, then slowly lowering the temperature to 0-10° C., and continuing to stir for 0.5-3 hours to precipitate crystals.
(3) Preparation of high-purity linezolid crystals
The precipitated crystals were separated in a three-in-one plate filtration, washing and drying process to obtain the crystalline form I of linezolid. Starting from the simplification of the process, the three processes of filtration, washing and drying are completed on one machine, which reduces the number of process transfers; starting from the automation, cleanability and sterilization, it is improved to make the overall process more suitable for Production of sterile APIs.
Sterile flat plate filter washing and drying three-in-one performance characteristics
The high-purity linezolid crystals prepared by the separation and purification of sterile-grade flat-plate filtration, washing and drying three-in-one antibiotic raw materials have compact crystal shape, good fluidity, low static electricity, and are easy to process. And other aspects are poor and other quality problems, has a wide range of market prospects.
1. Closed system: The three-in-one filter, washing and drying system is a fully closed system. Production and operation in the closed system can avoid air pollution from toxic substances, and at the same time reduce the occurrence of poisoning accidents by operators.
2. Recycling: materials and solvents are almost completely recovered, avoiding waste caused by material omission and solvent volatilization, which has great economic benefits.
3. Multifunctional integrated operation: filtering, washing and drying are completed in the same equipment.
The vessel walls are equipped with heating jackets to allow drying.
4. Continuous operation: Filtration and drying are carried out in a continuous system, no need to deal with wet filter cake. The dried products can be mechanically transferred to the weighing and packaging sections.
5. Saving manpower: a non-technical person who has undergone simple training can complete the operation. Opening, closing, automatic feeding and automatic discharging do not require technical personnel to monitor.
6. Thorough cleaning: The filter, washing and drying three-in-one has the functions of automatic spraying and stirring, and the filter cake can be fully cleaned, thereby reducing the amount of sewage and reducing the cost of wastewater treatment.
7. Clean production: The multifunctional filter drying system is equipped with a dust collector to collect the dust produced after drying, which can meet the requirements of clean production.
ZhangHua flat filter, washing and drying three-in-one customer site real photo display