PHARMA & BIOTECHNOLOGY
Purification in Pharma &
Biotech Industries
Centrifugal Partition Chromatography (CPC) is an advanced liquid–liquid chromatography technique widely applied in pharmaceutical and biotechnology workflows for the purification of complex molecules without the use of solid stationary phases. Its unique design enables gentle, non-denaturing separation, making it ideal for sensitive compounds such as peptides, proteins, oligonucleotides, and complex small molecules.
CPC integrates seamlessly into downstream processing steps, from post-extraction and clarification to intermediate purification and high-purity polishing. It is particularly powerful as part of a hybrid purification strategy, complementing other chromatographic and filtration techniques to maximize yield, purity, and process efficiency.
CPC offers several key advantages in pharmaceutical and biotech downstream processing:
Technology transfer and scalability: Straightforward method scale-up from the feasibility study, so laboratory scale to pilot and industrial scale without loss of resolution or selectivity.
Compliance with quality management standards: Integrated into GMP-compliant workflows and compatible with regulatory requirements for API manufacturing.
Green and sustainable: Solvent recyclability and the absence of solid waste significantly reduce environmental impact and operating costs (OPEX).
High selectivity and purity: Effective for chiral separations, diastereomer isolation, and enrichment of target compounds from complex matrices.
Process flexibility: Adaptable to a wide range of solvent systems and operating modes (ascending/descending, MDM) for optimal performance.
Cost efficiency: Eliminates the need for expensive solid supports, reduces solvent consumption, and minimizes consumable costs over time.
Peptides and Proteins
Centrifugal partition chromatography (CPC) offers a gentle, high-resolution approach for peptide and protein purification, avoiding the mechanical stress associated with solid-phase methods. Its liquid–liquid separation mechanism allows selective isolation of target molecules while preserving their structural integrity and biological activity.
CPC is highly effective at resolving closely eluting, sequence variants of peptides and other production-related impurities, which are challenging to separate using conventional chromatography. The method is scalable, cost-efficient, and compatible with food-grade or pharmaceutical-grade solvents, making it suitable for industrial applications. Overall, CPC provides a powerful, low-shear platform for producing high-purity peptides and proteins with minimal degradation or loss.
peptides & PROTEINS
+
Recombinant Human Albumin
Isolation of Recombinant Human Albumin (rHA)
Recombinant human albumin (rHA), is a key protein in biotech and a stabilizer and carrier in pharmaceutical formulations. It is traditionally purified using the costly Cohn fractionation method. Our study demonstrates a CPC-based aqueous two-phase process capable of producing >95% pure rHA in a single step, with 96% recovery and 2.5 g/h throughput. This approach offers a scalable, cost‑effective alternative for industrial protein purification.
+ Cyclosporin A
Isolation of Digoxin
Digoxin, a potent cardiac glycoside API from Digitalis lanata used to treat heart failure and arrhythmias, is difficult to purify due to structurally similar impurities like mono-/bisdigitoxosides, digoxigenin, and gitoxin.
CPC can be effectively applied as a single-step, high-selectivity solution using an optimized chlorinated solvent system, achieving >98% purity, 98% recovery, and 1 g/h throughput, delivering high yield, scalability, and cost efficiency.
ACTIVE PHARMACEUTICAL INGREDIENTS (APIs)
Centrifugal partition chromatography (CPC) provides a versatile and scalable solution for the purification of active pharmaceutical ingredients (APIs), offering high selectivity and yield.
Its liquid–liquid separation mechanism allows gentle processing, minimizing degradation of sensitive APIs and maintaining product integrity. CPC effectively resolves closely related impurities, such as isomers, stereoisomers, or synthesis byproducts, which are often challenging for conventional solid-phase chromatography. The method is compatible with a wide range of solvents, including pharmaceutical-grade systems, and can be easily scaled from laboratory to industrial production.
Overall, CPC enables cost-effective, high-purity API isolation, supporting both research-scale development and large-scale manufacturing.
Active Pharmaceutical Ingredients (APIs)
+ Anastrozole
Purification of Anastrozole
Anastrozole is a potent nonsteroidal aromatase inhibitor used in oncology, replacing labor-intensive column chromatography. An ether-based solvent system with centrifugal partition chromatography (CPC) on an rCPC device achieved 1 g/h throughput, >99% purity in one step, and 75% recovery.
A single crystallization raised purity to >99.9%, proving CPC’s cost-effective, scalable, high-performance potential for industrial API production.
+ Digoxin
Isolation of Digoxin
Digoxin, a potent cardiac glycoside API from Digitalis lanata used to treat heart failure and arrhythmias, is difficult to purify due to structurally similar impurities like mono-/bisdigitoxosides, digoxigenin, and gitoxin.
CPC can be effectively applied as a single-step, high-selectivity solution using an optimized chlorinated solvent system, achieving >98% purity, 98% recovery, and 1 g/h throughput, delivering high yield, scalability, and cost efficiency.
+ Steroids
Isolation of a Steroid API
This steroid API, produced via microbiological fermentation, often contains stereoisomers and by-products that make purification challenging, with conventional methods like multi-step processing and preparative HPLC causing yield losses up to 70%.
Using CPC with a precision-engineered ternary solvent system, we achieved 98.7% purity, 76% recovery, and 320 g/h throughput, delivering scalable, efficient, and cost-effective large-scale purification.
+ 10 DAB-III
Isolation of 10 DAB-III
10-Deacetylbaccatin III (10-DAB III), a key precursor for the anticancer drug docetaxel, is difficult to purify due to structurally related taxanes in crude Taxus baccata extracts.
Using CPC with an optimized ketone-based solvent system, we achieved 99% purity, 95% recovery, and 2 g/h throughput. This single-step, scalable method eliminates multiple purification stages, boosting efficiency and reducing costs for industrial taxane production.
Isomer separation
Centrifugal Partition Chromatography (CPC) provides an efficient solution for separating closely related isomers, which are often difficult to resolve with conventional chromatography.
Its liquid–liquid system allows precise tuning of partition coefficients, enabling selective isolation of individual stereoisomers or structural variants without degradation. High purity and selectivity can be achieved by exploiting different operating modes, such as ascending or descending mode, Multiple Dual-Mode (MDM) strategies, or pH-zone refining.
In CPC, both liquid phases’ pH can be adjusted without damaging the stationary phase or equipment. This gentle, low-shear technique ensures high purity and recovery, making it ideal for sensitive compounds in pharmaceutical and natural product applications.
Isomer Separation
+ Nebivolol
Chiral Separation of Nebivolol
Nebivolol, a Chromane Epoxide and a selective β₁-blocker with nitric oxide–mediated vasodilatory effects, requires challenging separation of its diastereomeric epoxide precursors due to their structural similarity.
Using CPC with an optimized alkane/alcohol/water system, we achieved >99% purity and >90% recovery for both isomers from a 57%/31% mixture at 14.4 g/h. The method is simple, recyclable, and scalable, offering an efficient solution for complex chiral precursor purification.
+ Remdesivir
Diastereomer Separation of Remdesivir Prodrug
Remdesivir, a COVID-19 antiviral prodrug, exists as SP- and RP-diastereomers, with only the SP form being clinically approved. We developed an achiral CPC method to efficiently separate these P-diastereomers, matching chiral HPLC selectivity while offering scalability and cost savings.
Using advanced Multiple Dual-Mode and trapping-MDM CPC, pilot-scale runs achieved >99% purity with high yields, enabling rapid, industrial-scale antiviral manufacturing.
Oligonucleotides &
Lipid-Based Delivery Systems
Lipid-Based Delivery Systems
Oligonucleotides and lipid-based delivery systems represent some of the most critical building blocks of modern nucleic acid therapeutics. Centrifugal Partition Chromatography provides a gentle, scalable, and solid-phase-free purification platform ideally suited for these sensitive molecules.
In oligonucleotide processing, CPC enables high-purity isolation of single-stranded DNA or RNA fragments, with excellent recovery and reproducibility.
In the field of drug delivery, CPC is applied to lipid nanoparticles (LNPs) and their individual components, ensuring the removal of closely related by-products while maintaining molecular stability. This includes the purification or fractionation of complete LNP carriers for mRNA delivery, as well as key lipid excipients. Together, these applications demonstrate how CPC empowers the production of high-quality nucleic acid therapeutics at both laboratory and industrial scales.
Oligonucleotides & LNP
+ Single-stranded oligo
Purification of synthetic DNA/RNA fragments
A 20-mer single-stranded unmodified oligonucleotide with an initial purity of 88.5% was purified using scalable ion-exchange centrifugal partition chromatography (IEX-CPC). The method, employing a water–organic two-phase solvent system, achieved 96.6% purity with 94.5% yield in a single step.
Subsequent lyophilization and alcohol precipitation efficiently removed solvents, salts, and additives, providing high-quality material suitable for pharmaceutical applications.
+ Lipid nanoparticles
Purification of lipid-based carriers for mRNA and nucleic acid delivery
Ionizable cationic lipids, essential components of lipid nanoparticles (LNPs) for mRNA vaccine delivery, were isolated from a complex synthetic mixture using a multiple dual mode (MDM) CPC method.
This method preserved lipid stability and outperformed normal-phase flash chromatography, yielding the target lipid at 93% with 98% purity from 320 mg crude in just 35 minutes.
