Amoxicillin crystal filtration, washing and drying integrated machine

Amoxicillin (a broad-spectrum penicillin antibiotic) is a white or off-white crystalline powder with a slightly bitter taste. It is slightly soluble in water but insoluble in ethanol. This product can inhibit the synthesis of the outer cell wall of bacteria and has a strong bactericidal effect on both Gram-positive and Gram-negative bacteria. Its antibacterial effect on Gram-positive bacteria is the same as or lower than that of Penicillin, but it has a stronger effect on Gram-negative bacteria such as Neisseria gonorrhoeae, Haemophilus influenzae, Bordetella pertussis, Escherichia coli, Brucella, etc. It is mainly used in clinical practice for infections of the urinary system, respiratory system, biliary tract, etc.

In 1987, the drug entered the list of the world's top 50 best-selling drugs by sales, ranking 31st with sales of 275 million US dollars. In 1996, it ranked 15th with sales as high as 1.384 billion US dollars. So far, it has remained the world's best-selling drug for more than ten consecutive years and ranks first among the world's anti-infective drugs.

The products produced by the existing amoxicillin process in China have small average particle size, high coefficient of variation, high impurity residue and poor product stability. The shelf life of domestic manufacturers is two years, while the international standard is over three years. The improvement of product quality and stability is mainly achieved through the following approaches:

(1) Strengthen personnel training to achieve stability in process technology control;

(2) Enhance the degree of process automation control; Technological transformation for the process applicability of equipment;

(3) Control the quality and stability of raw and auxiliary materials, especially the quality of the main raw materials 6-APA and potassium p-hydroxyphthalic anhydride.

(4) Optimization of process parameters for each main reaction step;

(5) The application of inspection technology in process control and the progress in the analysis of impurities in finished products have clarified the direction and provided a basis for improving product quality and process.

The quality of crystallization in production is manifested in the purity of the crystal, the size of the particles and the crystal form. The crystal particles should not be too fine; otherwise, the subsequent washing, filtration and separation will be difficult, affecting production efficiency, product yield and quality, resulting in high residual impurities in the product and poor product stability. Moreover, fine particles carry static charges, causing difficulties in the formulation processing of the product. In addition, if the particles are too small, the specific volume is too large and the fluidity is poor, these also bring inconvenience to the sub-packaging of the product. Therefore, improving the crystal form, particle size and particle size distribution of the product is one of the ways to enhance the purity and stability of the product as well as the applicability of the formulation.

The multi-functional integrated machine for crystallization, filtration, washing and drying is used in the refining and purification process steps of amoxicillin

Compared with the existing technology, the advantages of the multi-functional integrated machine for crystallization, filtration, washing and drying in the amoxicillin refining and purification process lie in: less colored impurities, high amoxicillin yield, good product quality, and the recovery of qualified phenylacetic acid, which is easy to be applied in production.

(1) Extraction steps

Cool the reaction solution and then add dichloromethane. Under stirring conditions, add hydrochloric acid with a mass concentration of 20 to 30% to separate the dichloromethane phase. Secondary and tertiary extractions were carried out to ultimately obtain the extracted aqueous phase containing 6-APA, which was combined with the dichloromethane phase.

(2) Preparation steps of the amoxicillin reaction

Ammonia water was added to the extracted aqueous phase containing 6-APA, and the residual dichloromethane in the extracted aqueous phase was removed under reduced pressure at room temperature. The obtained dessolute 6-APA solution was subjected to filtration and concentration. The crude amoxicillin was isolated through a synthetic reaction. Steps

(3) Acidification dissolution

Under the stirring of the main shaft of the multi-functional integrated machine for crystallization, filtration, washing and drying, hydrochloric acid with a mass concentration of 20-30% is added to the crude amoxicillin product to completely dissolve the amoxicillin, and then filtration is carried out.

(4) Crystallization

Under cooling conditions, ammonia water with a mass concentration of 6% to 10% was added to the amoxicillin solution, and the pH of the feed solution was controlled at 4.8 to 5.2. Crystals were grown for 90 to 120 minutes under cooling conditions.

(5) Filtration, washing and drying

The amoxicillin crystal liquid was subjected to vacuum filtration using a multi-functional integrated machine for crystallization, filtration, washing and drying. It was then washed with purified water and acetone respectively. Subsequently, the wet amoxicillin powder was subjected to vacuum low-temperature drying at a temperature of 40 to 60℃ with a vacuum degree of ≥0.085MPa. After the drying process was completed, the dry amoxicillin powder was obtained.

Photos of the multi-functional integrated machine for crystallization, filtration, washing and drying in the amoxicillin refining and purification equipment