Nanomembranes are a type of nanomaterial with ultra-thin structures at the nanometer scale and lateral dimensions that can extend to millimeters or even centimeters. These membranes are strong enough to remain self-supporting and have unique features, such as nanoscale pores, high surface area, and material versatility, making them valuable for various applications.
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The high porosity of nanomembranes enhances their permeability and bioactivity, making them particularly effective for separation and purification processes.1 These properties are especially valuable in the pharmaceutical industry, as nanomembranes provide efficient and sustainable solutions for separation and purification.
Traditional separation methods, like distillation, are energy-intensive and contribute to 10-15 % of global energy consumption. In contrast, nanomembrane-based separation offers a low-energy, low-carbon alternative for purifying high-value products and recovering solvents used in pharmaceutical manufacturing.2
The Science Behind Nanomembrane Separation
Nanomembranes use their nanoscale pore structures and distinct surface characteristics to efficiently separate substances. They differentiate molecules based on size, charge, and other molecular properties using two primary transport models: the pore-flow model and the solution-diffusion model.2,3
- Pore-Flow Model: Separation occurs via size exclusion, where smaller solutes pass through the pores while larger ones are rejected.2,3
- Solution-Diffusion Model: This involves the dissolution of solutes into the membrane material, followed by diffusion driven by a concentration gradient.2,3
Selectivity is further influenced by interactions between solutes, solvents, and the membrane itself, governed by factors such as solute diameter, pore wettability, and charge effects. Compared to traditional filtration methods, nanomembranes provide higher selectivity and efficiency while operating at lower energy levels and under milder conditions.4
Their ability to precisely control molecular separation, coupled with their high permeability and versatility, makes nanomembranes essential in applications requiring high-purity outputs, such as pharmaceutical separation and purification.2,4
Applications in Pharmaceutical Separation
Purification of Active Pharmaceutical Ingredients
Nanomembranes are an essential tool in the purification of active pharmaceutical ingredients (APIs), helping to efficiently remove impurities such as organic byproducts, inorganic residues, and leftover solvents. These impurities often originate during chemical synthesis, fermentation, or extraction processes and must be eliminated to ensure drug safety and efficacy.2
Traditional purification methods, like distillation and chromatography, are energy-intensive and can degrade sensitive APIs due to high temperatures. Organic Solvent Nanofiltration (OSN) membranes offer a low-energy, scalable alternative. Operating under mild conditions, OSN membranes use a process called diafiltration to separate impurities—such as genotoxic substances—from APIs, which are retained by the nanomembrane.2,5
This method lowers energy consumption, reduces solvent use, and enhances yield and purity, making it a sustainable option for pharmaceutical manufacturing.
Separation of Biomolecules
Nanomembranes play a vital role in the isolation and purification of biomolecules such as proteins, peptides, and other macromolecules—key components in the development of biologic drugs. By providing precise control over molecular size, charge, and polarity, nanomembranes enable efficient separation processes critical to drug development.1,6
Materials such as polylactic-co-glycolic acid (PLGA) and graphene oxide are commonly used in nanomembrane design due to their excellent biocompatibility and mechanical strength, qualities that help preserve the integrity of sensitive biomolecules during processing.6,7
Hybrid nanomembranes, which combine organic and inorganic materials like titanium dioxide (TiO2), zinc oxide (ZnO), polyacrylonitrile (PAN), and polyamide, offer additional advantages. Functionalized conductive graphene (FCG) and silver (Ag)-based membranes, for example, enhance the separation of complex biomolecules during peptide and protein synthesis.
Nanomembranes are also used in applications like tissue engineering and drug delivery, where their selective permeability supports controlled therapeutic agent release.1,8
Removal of Contaminants
The safety of pharmaceutical products depends on effectively removing contaminants like endotoxins, bacteria, and viruses. Nanomembranes with functionalized surfaces are particularly well-suited for this purpose. For example, virus removal filters with pore sizes smaller than 20 nm are used to purify blood plasma products and vaccines.9
Nanomembranes with hydrophilic coatings are also effective at removing endotoxins—bacterial toxins that can trigger severe immune reactions. This function is especially important in the production of injectable drugs, where even trace amounts of contaminants can have significant health implications.10
Precision nanofiltration for organic solvent separation for the pharmaceutical industry
Strengths and Limitations of Nanomembrane Systems
Nanomembranes provide efficient and precise separation capabilities, helping to improve the yield and quality of pharmaceutical products. Their nanoscale pore structures enable selective separation based on size, charge, or other molecular properties, making them a reliable option for complex purification processes.1,2
Another advantage is that they operate at lower energy levels compared to traditional methods like distillation or chromatography, reducing costs and environmental impact. Advanced fabrication techniques, such as chemical vapor deposition and layer-by-layer deposition, enable the creation of nanomembranes with well-ordered pores, enhancing performance and adaptability for various pharmaceutical applications.1,11
However, there are challenges that limit their broader adoption in pharmaceutical manufacturing. Membrane fouling, where pores become clogged with contaminants, can reduce efficiency over time. Limited mechanical strength and lifespan, especially in highly porous membranes, also hinder their durability and reliability in industrial applications.11
Scalability remains a major obstacle, as methods like lithography and micromachining are expensive and difficult to implement for large-scale production. Additionally, achieving sufficient separation performance for solutes with similar molecular weights or removing small solutes below 200 Da is technically challenging. Automation and continuous process control in industrial settings also need further development.11
Advancing Nanomembrane Technology for Pharmaceutical Applications
Research is focused on developing more durable materials and improving fabrication techniques to address challenges. For instance, hybrid nanomembranes made from combinations of inorganic and organic materials, such as poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotube sheets (CNS), offer improved mechanical strength and biocompatibility.12
Improved regeneration techniques, such as cleaning protocols to reduce fouling, can extend membrane lifespan. Implementing membrane cascades—where membranes are used in a series—can improve separation efficiency while minimizing solvent use.11
Advances in scalable manufacturing techniques, including improvements in 3D printing resolution and more cost-effective chemical vapor deposition, will facilitate large-scale production. Additionally, the use of predictive models for performance and sustainability metrics, like energy consumption and carbon footprint, will support the optimization of nanomembrane systems for industrial applications.1,11
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References and Further Reading
1. Ciganė, U.; Palevičius, A.; Janušas, G. (2021). Review of Nanomembranes: Materials, Fabrications and Applications in Tissue Engineering (Bone and Skin) and Drug Delivery Systems. Journal of Materials Science. https://link.springer.com/article/10.1007/s10853-021-06164-x
2. Xiao, H.; Feng, Y.; Goundry, WR.; Karlsson, S. (2024). Organic Solvent Nanofiltration in Pharmaceutical Applications. Organic Process Research & Development. https://pubs.acs.org/doi/10.1021/acs.oprd.3c00470
3. Marchetti, P.; Jimenez Solomon, MF.; Szekely, G.; Livingston, AG. (2014). Molecular Separation with Organic Solvent Nanofiltration: A Critical Review. Chemical reviews. https://pubs.acs.org/doi/10.1021/cr500006j
4. Huang, G.; Mei, Y. (2018). Assembly and Self‐Assembly of Nanomembrane Materials—from 2d to 3d. Small. https://pubmed.ncbi.nlm.nih.gov/29292590/
5. Szekely, G.; Amores de Sousa, MC.; Gil, M.; Castelo Ferreira, F.; Heggie, W. (2015). Genotoxic Impurities in Pharmaceutical Manufacturing: Sources, Regulations, and Mitigation. Chemical reviews. https://pubmed.ncbi.nlm.nih.gov/26252800/
6. He, Y.; Qin, L.; Fang, Y.; Dan, Z.; Shen, Y.; Tan, G.; Huang, Y.; Ma, C. (2020). Electrospun Plga Nanomembrane: A Novel Formulation of Extended-Release Bupivacaine Delivery Reducing Postoperative Pain. Materials & Design. https://www.sciencedirect.com/science/article/pii/S0264127522011649
7. Mao, Z.; Li, J.; Huang, W.; Jiang, H.; Zimba, BL.; Chen, L.; Wan, J.; Wu, Q. (2018). Preparation of Poly (Lactic Acid)/Graphene Oxide Nanofiber Membranes with Different Structures by Electrospinning for Drug Delivery. RSC advances. https://pubs.rsc.org/en/content/articlelanding/2018/ra/c8ra01565a
8. Yang, L.; Wei, J.; Ma, Z.; Song, P.; Ma, J.; Zhao, Y.; Huang, Z.; Zhang, M.; Yang, F.; Wang, X. (2019). The Fabrication of Micro/Nano Structures by Laser Machining. Nanomaterials. https://www.mdpi.com/2079-4991/9/12/1789/review_report
9. Koenderman, A.; Ter Hart, H.; Prins-de Nijs, I.; Bloem, J.; Stoffers, S.; Kempers, A.; Derksen, G.; Al, B.; Dekker, L.; Over, J. (2012). Virus Safety of Plasma Products Using 20 Nm Instead of 15 Nm Filtration as Virus Removing Step. Biologicals. https://www.sciencedirect.com/science/article/abs/pii/S104510561200111X?via%3Dihub
10. Dhas, N.; García, M. C.; Kudarha, R.; Pandey, A.; Nikam, AN.; Gopalan, D.; Fernandes, G.; Soman, S.; Kulkarni, S.; Seetharam, RN. (2022). Advancements in Cell Membrane Camouflaged Nanoparticles: A Bioinspired Platform for Cancer Therapy. Journal of Controlled Release. https://pubmed.ncbi.nlm.nih.gov/35439581/
11. Haque, SR. (2023) Preparation, Characterization, Applications and Future Challenges of Nanomembrane-a Review. Hybrid Advances. https://www.sciencedirect.com/science/article/pii/S2773207X23000106?via%3Dihub
12. Kim, K. J.; Lee, JA.; Lima, MD.; Baughman, RH.; Kim, SJ. (2016). Highly Stretchable Hybrid Nanomembrane Supercapacitors. RSC advances. https://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra02757a
