Application of Membrane Separation Technology in Antibiotics Production

1. Brief introduction of membrane technologies used in antibiotics production

Membrane separation technology is a combination of material science and media separation technology, which has the advantages of high efficiency, precision separation, simple equipment, energy saving, normal temperature operation, and no pollution. It is widely used in the industrial field, and it has developed rapidly in the fields of food, medicine, and biochemistry. In recent years, the extraction of antibiotics has become one of the key promotion areas of membrane separation technology, which has been deeply researched. Membrane separation technology replaces traditional separation and purification technology, which can simplify the production process of antibiotics, save organic solvents, reduce the degradation of the target product during the extraction process, increase product yield, and reduce environmental pollution. At present, membrane separation technology is mainly used for clarification of fermentation broth, product concentration and desalination, and concentration of antibiotics in waste liquid.

Generally, the molecular weight of antibiotics is between 200-1000 while the molecular weight of the soluble protein in the fermentation broth is generally tens of thousands to hundreds of thousands, and the particle size of the suspended matter and fermentation by-products in the fermentation broth is also relatively large, which can be separated and extracted by membrane separation technology. At the same time, it can remove part of the inorganic salt in the feed liquid.

2. The process of membrane separation technology applied in extraction and purification of antibiotics (taking CPC as an example)

Antibiotic extraction process:

fermentation broth → filtration or centrifugal separation or macroporous resin adsorption → extraction → concentration → decolorization → drying → product

It can be simplified by membrane separation technology process:

fermentation broth → ultrafiltration → nanofiltration (or reverse osmosis) → decolorization → drying → product

3. Advantages of membrane separation technology compared to the traditional process

Compared with the traditional extraction process, the advantages of membrane separation technology are as follows:

(1) It greatly simplifies the process, with less one-time investment, simple maintenance, simple operation, low operating costs, saving a lot of human and material resources.

(2) Membrane separation technology has no phase change in operation and high concentration ratio, which greatly saves energy such as cold brine, steam, electricity, and vacuum. And it has high separation efficiency without damage to the structure of the product, and can more completely remove solid particles in the liquid, soluble proteins, peptides, bacteria, pyrogens and most pigments. Since it can realize the fully enclosed operation, the secondary pollution of the system is reduced, so that the material liquid is more transparent, the titer is higher, and the yield and quality of the product are improved.

(3) The solvent is not needed or its amount is greatly reduced, and the replacement cycle of activated carbon in decolorization is extended several times. Wastewater is easier to treat, and the investment and operating costs of wastewater treatment will be greatly reduced, which is more beneficial to environmental protection.

In summary, if we use membrane separation technology to extract antibiotics, the process will be greatly simplified, the energy consumption will be greatly reduced with small demand of solvent, the yield will increase from 70%-80% to more than 88%, and the potency and quality of the medicine will also be improved.

The separation of antibiotic fermentation broth sometimes requires 1 to 3 membrane separation operations. The first step of solid-liquid separation is usually microfiltration or ultrafiltration to obtain the permeate containing antibiotics, salt and water. The quality of the permeate determines the choice of the subsequent method. Sometimes it is necessary to use ultrafiltration again and then concentrate by nanofiltration. The need for intermediate purification depends on the solvent extraction results of concentrated antibiotics. If the extraction results are satisfactory after only one ultrafiltration and nanofiltration, intermediate purification is not necessary, otherwise an intermediate purification is required.

(1) Combined separation of ultrafiltration and nanofiltration membranes

6-Aminopenicillanic acid (6-APA) is the key raw material for the production of semi-synthetic penicillin. Treat the potassium salt of 6-APA with ultrafiltration membrane, after cracking in the reaction tank, adjust the pH of the reaction solution to 7.5～8.8 with 3mol/L ammonia to complete the cracking at a certain temperature, and then concentrate thorough the nanofiltration membrane, with the cracking rate of 97.5%.

(2) Ultrafiltration, nanofiltration and phase inversion combined separation

The combined separation technology of ultrafiltration, nanofiltration and phase inversion is used to purify and concentrate the lincomycin fermentation broth, shorten and optimize the traditional process, greatly save solvent and energy, as well as improve the yield and quality.

4.The prospect of membrane separation technology in antibiotics production

Membrane separation has become an important means of technological innovation in the modern pharmaceutical industry. With the continuous improvement of product quality requirements and the continuous reduction of production cost requirements, the advantages of membrane technology are becoming more and more outstanding, and it will surely replace the traditional inefficient separation technology. However, a large number of applications of membrane separation technology have only begun in recent decades. Although the current research is very active, most of them are in the experimental stage, there are still some limits in practical applications.