Ceramic Membranes: Precision Tools for Biopharma Breakthroughs

The biopharmaceutical industry has very strict requirements for separation and purification systems during production. These systems must be able to withstand high temperatures, corrosive solvents, strong acids, strong alkalis, high feed solid content, high viscosity, and other harsh operating conditions. Due to its unique characteristics such as bacterial resistance, high temperature resistance, and chemical stability, ceramic membranes have become the preferred separation technology in the biopharmaceutical industry.

Overview of Ceramic Membranes

Ceramic membranes are inorganic membranes formed through special processes. They commonly use inorganic ceramic materials such as Al2O3, ZrO2, TiO2, SiC, SiO2, and their combinations as raw materials. Ceramic membrane pore sizes cover the entire range of membrane pore sizes, including microfiltration (pore size >50nm), ultrafiltration (2nm < pore size <50nm), and nanofiltration (pore size <2nm). Currently, commercialized ceramic membranes generally come in five types: plate, spiral wound, tubular, hollow fiber, and capillary. All types of ceramic membranes generally have a three-layer structure: the bottom layer is a loose porous support that provides mechanical strength to the entire membrane without affecting the flux. It is prepared by dry pressing or slip casting and solid-state particle sintering; above the support layer is the intermediate layer, and then the separation layer, where the membrane pores gradually become smaller, playing a selective permeation function through pore size screening. This is mostly prepared by slip casting and sol-gel method.

Development History of Ceramic Membranes

Ceramic membranes originated in the 1940s. They refer to asymmetric membranes formed by processing ceramic materials. As early as World War II, they were used in the separation of uranium isotopes and were part of military nuclear industry research. By the 1980s, ceramic membranes entered the liquid separation stage, mainly using microfiltration and ultrafiltration membranes. By the 1990s, ceramic membranes experienced rapid development in gas separation and the combination of ceramic membrane separators and reactors.

Advantages of Ceramic Membranes

Ceramic membranes are rigid materials with high mechanical strength. They maintain their complete pore structure under high pressure, unlike polymer membranes which can deform and affect filtration performance. Under the same pore size conditions, ceramic membranes can operate under high pressure, and their permeation flux can reach twice that of polymer membranes, resulting in higher efficiency.

Ceramic membranes have good antifouling properties and high permeation flux. The inorganic material composition of ceramic membranes provides good hydrophilicity, giving them good antifouling properties. In addition, ceramic membranes are resistant to high temperatures and can operate under high-temperature conditions, reducing the impact of high-viscosity materials on permeation flux. Therefore, ceramic membranes have stronger antifouling properties and can effectively maintain stable permeation flux.

Ceramic membranes have high cleaning efficiency. First, due to the hydrophilicity of ceramic membranes, they are easily cleaned online with simple water or chemicals, maintaining good flux for a long time. Second, due to their strong acid and alkali resistance, ceramic membranes can undergo deep cleaning, improving cleaning efficiency. In the sugar industry, high-viscosity sugars tend to choose ceramic membrane separation technology. Ceramic membranes have good chemical and mechanical stability and can typically use NaOH and NaClO to remove proteins, polysaccharides, and suspended impurities from fouled ceramic membranes, loosening and decomposing the deposits and gel layers on the membrane surface, with a flux recovery rate of over 95%.

Preparation Methods of Ceramic Membranes

(1) Dip Coating Method: The dip coating method involves forming a stable and uniformly dispersed suspension of powder, dispersant, and binder. The ceramic support is immersed in the suspension for a certain period of time and then removed. Under the action of capillary force and adhesion, the substances in the suspension form a filtration layer on the surface of the ceramic support. After drying and curing, sintering forms the ceramic membrane. This method is simple to operate, but the formation of a high-quality membrane layer is related to the viscosity of the suspension, the immersion time, the withdrawal rate, and the support structure. The support needs to have an appropriate pore size and distribution and a smooth surface, and a certain porosity ensures the slurry absorption performance during the film-forming process.

(2) Sol-Gel Method: The sol-gel method is a common method for preparing ceramic membranes with nanopores. This method uses metal alkoxides or inorganic salts as precursors. Hydrolysis and condensation reactions occur in the solution to form a stable sol, which is then coated onto the support surface. After drying, a gel is formed, and finally, low-temperature sintering forms the membrane. The sol-gel method can prepare ceramic membranes with nano-scale pores, but there is a problem of difficulty in sintering to a dense structure.

(3) Chemical Vapor Deposition (CVD) Method: Chemical vapor deposition is a method where chemical reactions occur between gaseous substances at a certain temperature and pressure, and a film is deposited on the substrate surface. This method can achieve control of the pore size of microporous membranes and form dense membranes, and can form membranes on supports with complex shapes. This method is complex to operate, requires expensive equipment, and is not suitable for large-scale commercial production.

(4) Anodization Method: The anodization method uses electrochemical principles to form a membrane on the surface of the support, most commonly used for the preparation of Al2O3 and TiO2 separation membranes. The main principle is to use metal as the anode, place it in an acidic electrolyte solution, and apply an external current. The transfer of electrons causes the metal to undergo an electrolytic reaction, forming a dense oxide layer on one side of the metal membrane. The anodization method can form pores of 10-25 nm, but due to equipment limitations, this method is not suitable for large-scale industrial use.

Applications of Ceramic Membranes in the Biopharmaceutical Field

Ceramic membranes have become the preferred separation technology in the biopharmaceutical industry, replacing traditional refining technologies such as adsorption, precipitation, solvent extraction, and ion exchange. The pharmaceutical field is the largest consumer of ceramic membranes, accounting for 30.0% of demand. Compared with polymer membranes, ceramic membranes have better repeat steam sterilization capabilities and are easier to clean with harsh chemicals, fully meeting the sterile requirements of pharmaceutical production. Therefore, their applicability in the pharmaceutical industry is increasing.

(1) Fermentation Broth Filtration and Target Product Concentration: Currently, ceramic membrane separation and purification technology is used in the antibiotic industry production of major pharmaceutical companies. Antibiotics such as erythromycin, cephalosporins, and vancomycin all use this technology. Antibiotics are mainly synthesized by microbial fermentation, with a content of 0.1-5 (w/v)% in the fermentation broth, and a molecular weight of 300-1200 Da. Microfiltration can be used to remove bacteria from the fermentation broth, ultrafiltration for clarification, and nanofiltration for concentration or screening of antibiotics.

(2) Pyrogen Removal in the Pharmaceutical Industry: Currently, there are two conventional methods for pyrogen removal in the pharmaceutical industry: one method uses high-temperature sterilization to remove pyrogens from materials, but this method has high energy consumption and costs. Another method uses adsorbents, but the efficiency of pyrogen removal by adsorption is relatively low, and the regeneration of the adsorbent is also difficult. Ceramic membranes can effectively remove pyrogens without affecting the active ingredients in the product, significantly improving product quality and yield, reducing production costs, and increasing economic benefits.

(3) Preparation of Sterile Clean Air for Fermentation: Utilizing the uniform pore size, anti-pollution, and easy-cleaning properties of inorganic ceramic membranes, bacteria, particles, and other polluting impurities can be intercepted from the gas phase to achieve sterilization and purification. This is used to prepare sterile clean air for biofermentation and for the treatment of gases in sterile rooms. This solves the problems of leakage of bacteria and the inability to intercept viruses and pyrogens that exist in clean air preparation using other equipment, providing a new and effective method for the preparation of clean air for pharmaceutical use.

(4) Enzyme Isolation and Extraction: Traditional separation and extraction methods such as centrifugation, precipitation, dialysis concentration, and desalting result in enzyme solutions with relatively low enzyme activity, requiring further concentration. These methods have drawbacks such as multiple steps, high energy consumption, easy inactivation, and low recovery rates. Ceramic membrane technology has advantages such as simple equipment, convenient operation, high processing efficiency, and energy saving. It can separate high concentrations of cells in a short time without enzyme activity loss. Using ceramic membrane separation technology can simplify the extraction, purification, and desalting procedures of enzymes, shortening the time, reducing labor intensity, lowering costs, and improving product quality and stability. This offers advantages unmatched by traditional processes.

(5) Treatment of Wastewater from Biopharmaceutical Production: Wastewater treatment from biopharmaceutical production is a challenge in environmental protection. The wastewater is intermittently discharged, has a high pollution load, and has a complex composition. Due to the presence of antibacterial effects, traditional biochemical treatment methods are difficult to solve this problem. The ceramic membrane bioreactor is a new technology applying biotechnology and membrane separation technology to wastewater treatment. It is a new and efficient wastewater treatment process. It has advantages such as good treated water quality, small footprint, high sludge concentration, simple operation, and easy automation. It provides a reliable new method for wastewater treatment and water resource reuse in the biopharmaceutical industry.

Summary: Ceramic membranes have broad development prospects in the biomedical field. For biopharmaceuticals, ceramic membranes can meet the requirements of low temperature, sterility, and anti-pollution in the separation and purification process of their products, with advantages unmatched by other separation equipment. However, the application of ceramic membrane separation technology in the biopharmaceutical field still faces challenges. The search for highly reliable materials and the development of new preparation technologies to produce high-precision ceramic membranes with low pore size and narrow pore size distribution will also broaden the application of ceramic membrane separation technology in the biopharmaceutical field.
 

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Source: China Powder Network