Application of membrane separation technology in pharmaceutical purification process

In the cost structure of pharmaceutical products, separation, purification and concentration account for a high proportion. The application of modern separation, purification and concentration technology is an important way to improve the economic benefit of pharmaceutical industry or reduce investment. Membrane separation process is usually operated at room temperature, so it has no phase change and low energy consumption. It is especially suitable for the treatment of thermosensitive substances in pharmaceutical industry. The proper membrane separation process can replace many traditional separation and filtration methods, such as drum vacuum filtration, plate and frame pressure filtration, bag filtration, centrifugal separation, electrostatic precipitation, flocculation, sedimentation, ion exchange, solvent extraction, adsorption / regeneration, evaporation, crystallization, etc. Therefore, the pharmaceutical industry is increasingly using membrane separation technology, different membrane processes have different applications in pharmaceutical production. In this paper, the application of membrane separation technology in pharmaceutical industry will be described from three aspects: biological fermentation pharmaceutical, traditional Chinese medicine production and modern biopharmaceutical.

1、 Application of biofilm separation in pharmaceutical industry

1.1 characteristics of biological fermentation broth

In pharmaceutical industry, antibiotics, vitamins and amino acids are mainly produced by biological fermentation. However, the concentration of the target product in the fermentation broth is very low (generally only about 0.1-5% of the volume of the fermentation broth, and some are even lower), and there are a lot of other impurities, such as mycelium, residual soluble substrate, intermediate metabolites, substances added in the pretreatment process of the fermentation broth, etc. the concentration of these impurities in the fermentation broth is often 100, 1000, or even 10000 times higher than the concentration of the target product, Moreover, the physicochemical properties of many of the metabolites are very close to those of the target products, even the chemical composition is the same as that of the target products, only the stereoscopic configuration is different. In addition, the heat resistance, pH resistance and organic solvent resistance of the target product are poor, and it is easy to inactivate under mechanical shear force. Therefore, in order to remove these impurities from the fermentation broth and prepare high purity pharmaceutical products in line with the Pharmacopoeia, the extraction and purification of fermentation broth is a very important link.

1.2 application of membrane separation combined technology in the treatment of biological fermentation broth

When membrane separation technology is used to treat biological fermentation broth, first-order microfiltration or first-order ultrafiltration is usually used to remove macromolecular substances such as mycelium, protein, virus and pyrogen, while small molecular metabolites (including target products), salt and water pass through microfiltration or ultrafiltration membrane. Because the quality of microfiltration and ultrafiltration permeate is very important to the subsequent operation, it is necessary to carry out secondary ultrafiltration for the permeate of primary microfiltration or ultrafiltration in some industrial applications. The ultrafiltration process generally needs to add water for diafiltration to improve the yield. According to the specific separation system, the operation mode of diafiltration can be selected from batch, continuous or countercurrent filtration. Due to the low concentration of the target product in the ultrafiltration permeate, in order to save the solvent and energy consumption used in the follow-up process, and improve the yield and product quality, it is necessary to use one-stage or multi-stage nanofiltration or reverse osmosis for concentration before solvent extraction or evaporation drying.

Biological fermentation broth is a very complex solution system, and various compounds in the fermentation broth system affect the separation performance of membrane. Therefore, when the membrane separation technology is applied in industry, it is a very critical step to select the appropriate membrane through small-scale test and pilot test.

2、 Application of membrane separation technology in the production of traditional Chinese Medicine

2.1 urgent problems in the production of traditional Chinese Medicine

The chemical composition of traditional Chinese medicine is very complex. It usually contains inorganic salts, alkaloids, amino acids, organic acids, phenols, ketones, saponins, steroids and terpenoids, as well as proteins, polysaccharides, starch, cellulose and so on. Generally speaking, the high molecular weight substances are mainly colloids, fibrin and other non medicinal components or less medicinal components, and the relative molecular weight of the effective parts of drugs is relatively low Generally smaller.

At present, traditional Chinese medicine in China generally has the disadvantages of large dosage and unstable quality. The root cause is the backward extraction and separation technology in the production process of traditional Chinese medicine, which is characterized by complicated process, high cost, serious environmental pollution, high labor intensity, and low extraction rate of effective components. Therefore, in order to promote traditional Chinese medicine to the world market, we must carry out a revolutionary high-tech transformation of the traditional Chinese medicine industry, in which the membrane separation technology is considered as one of the high and new technologies that need to be promoted in China's traditional Chinese medicine pharmaceutical industry.

2.2 application status and Prospect

The molecular weight of ultrafiltration membrane ranges from 5000 to 500000, while the molecular weight of most effective components of traditional Chinese medicine is less than 1000, while the molecular weight of ineffective components such as starch, protein and resin is more than 50000. Therefore, the ultrafiltration membrane with a certain molecular weight can achieve the separation of effective components and impurities, and also can retain the original characteristics of traditional Chinese medicine, and play a great role in the efficacy.

At present, there are many reports about the application of ultrafiltration membrane in the production of traditional Chinese medicine

1) Extraction of effective parts of traditional Chinese medicine;

2) Production of oral liquid;

3) Preparation of extract preparation;

4) Removal of pyrogen;

5) Recovery of active components from pharmaceutical wastewater.

Due to the high content of viscous substances in traditional Chinese medicine, membrane fouling is serious. Therefore, appropriate membrane materials (such as anti fouling polyacrylonitrile, sulfonated polysulfone membrane, etc.), material liquid conditions, process parameters and cleaning methods should be selected to effectively control and reduce membrane fouling