Pharmaceutical Applications

Remdesivir: Explore a new purification method

Embark on a journey of innovation with us as we explore the transformative potential of Liquid Chromatography and Centrifugal Partition Chromatography in Remdesivir preparation. Join industry pioneers in ensuring your Remdesivir meets the utmost standards of quality, purity, and precision. Unlock a new level of excellence in pharmaceutical development.

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Advancing Nanoparticle Research

Lipid nanoparticles (LNPs) are crucial components in mRNA vaccine formulation in pharmaceutical drug delivery research, consisting of key lipid components. In a recent breakthrough, a novel solvent system-based method utilizing Continuous CPC was developed to isolate cationic lipids efficiently from complex synthetic mixtures. This method not only ensures the stability of the target lipid but also outperforms traditional chromatography techniques in terms of purity and yield.

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Preparative separation of diastereomer epoxides

CoI: Nebivolol

Goal: Separation

Nebivolol is a selective β1 adrenergic receptor antagonist with nitric oxide-mediated vasodilatory properties utilized in the treatment of hypertension. Diastereomers of an optically active substance are similar in structure, while they usually show significant differences in pharmacodynamic properties. Our study aimed to develop an achiral liquid-liquid chromatographic approach for the efficient and scalable separation of a diastereomer mixture of nebivolol precursors.

Our starting material consisted of about 57% isomer A epoxide and 31% isomer B epoxide among several other impurities. We found the optimal method parameters with lab-scale experiments. We screened several different binary and ternary solvent systems to find proper solubility, partition, and selectivity for the diastereomer pair. The optimized and tested alkane/alcohol/water biphasic liquid system is considered simple, recyclable, and easily applicable even on pilot-scale or industrial-scale CPC instruments. Using our optimized method on a pilot-scale, we managed to isolate both isomers with a throughput of 14.4 g/h, resulting in purity greater than 99% along with a high yield (>90%).

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Isolation Of Oligonucleotides By Scalable IEX-Centrifugal Partition Chromatography

CoI: 20-mer single-stranded unmodified oligonucleotide

Goal: Isolation

This study underscores the efficacy of centrifugal partition chromatography (CPC) in the pharmaceutical and biotechnology industries, offering high purity and yield in a single purification step, thus holding promise for industrial-scale production of oligonucleotides crucial in vaccine development and pharmacology.

The study was conducted to purify nucleotides, specifically a 20-mer single-stranded unmodified oligonucleotide, initially possessing 88.5% purity. Employing CPC, a two-phase solvent system of ethyl acetate/n-butanol/nuclease-free water was utilized. The 600 mg sample was injected into the system via an injection loop. This approach yielded a remarkable purity of 96.6% and a calculated yield of 94.5%. Furthermore, the method enabled removal of organic solvents through lyophilization, with residual salts and additives easily eliminated via alcohol precipitation, which resulted in a pure and ready-for-application material.

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Isolation of Mitragynine

Compound of Interest (CoI): Mitragynine

Goal: Isolation

Embark on a transformative journey in pharmaceutical research with our innovative feasibility study aimed at isolating mitragynine, particularly abundant in Mitragyna speciosa leaf extract. Kratom is therapeutically used for chronic pain, fatigue, anxiety, and is also consumed for recreational purposes. Further uses include treating opioid withdrawal symptoms. Mitragynine (MG), alongside closely related alkaloids such as speciogynine (SG), speciociliatine (SC), and paynantheine (PM), poses a significant challenge for purification due to their structural similarities. Another significant alkaloid found in kratom, which has a 52-fold higher relative potency of binding to μ-opioid receptors than MG, is the 7-hydroxy-mitragynine (7-OHMG) derivative. However, 7-OHMG makes the extract a health risk in kratom products, and removing it increases the safety of kratom products.

Traditional purification methods have proven cumbersome and resource-intensive, necessitating multiple steps for separation. However, our study presents a paradigm shift by leveraging the potency of centrifugal partition chromatography (CPC) on an rCPC device. Through meticulous experimentation, we have identified an ethereal-based solvent system, facilitating cost-effective isolation of MG with unmatched purity of 99% in a single step, and also removing 7-OHMG. With a throughput of 15 g/h and a high recovery rate of 81%, our method offers a streamlined and economically viable solution for safe and large-scale industrial production. This groundbreaking approach holds significant promise for advancing medicinal chemistry and pharmacology research in the domain of Kratom-derived alkaloids.

Isolation of plasma proteins

CoI: Recombinant Human Albumin (rHA)

Goal: Isolation

In the realm of pharmaceutical research, our feasibility study sets out to revolutionize the isolation process of recombinant human albumin (rHA), a pivotal protein utilized in various biotech and medical applications. Traditionally, the Cohn method has stood as the cornerstone for fractionation techniques; however, its widespread adoption is accompanied by substantial initial investment and maintenance costs.

Addressing these challenges, our study introduces a novel approach utilizing centrifugal partition chromatography (CPC), specifically tailored for the purification of rHA. Through meticulous experimentation, we have identified an aqueous two-phase solvent system, optimizing the separation process. With a notable throughput of 2.5 g/h, our method showcases the capability to produce rHA with a purity exceeding 95% in a single step. Furthermore, boasting a remarkable recovery rate of 96%, our approach promises efficiency and scalability for industrial-scale production. This pioneering method highlights the transformative potential of CPC technology in revolutionizing protein purification processes in pharmaceutical industries.

Polishing of a steroid API

API: Steroid

Goal: Purification

In the landscape of pharmaceutical research, our feasibility study aims to redefine the purification process of a crucial steroid Active Pharmaceutical Ingredient (API) derived from a microbiological fermentation process. Despite the efficacy of this fermentation process, issues arise when reaction selectivity is compromised, leading to the formation of stereoisomers and unwanted by-products. Traditional production techniques entail multiple steps, resulting in significant yield losses, particularly evident in the preparative High-Performance Liquid Chromatography (HPLC) step, where losses can reach 70%.

However, our innovative approach leverages centrifugal partition chromatography (CPC) to overcome these challenges. Through meticulous experimentation, we have identified a methyl isobutyl ketone/acetone/water solvent system, optimized for the efficient separation of the steroid API. With an impressive throughput of 320 g/h, our method demonstrates the capability to produce API with a remarkable purity of 98.7%. Furthermore, boasting a recovery rate of 76%, our approach ensures high yield while maintaining exceptional purity. This pioneering method not only enhances the efficiency of steroid API purification but also underscores the transformative potential of CPC technology in revolutionizing pharmaceutical production processes on an industrial scale.

Isolation of Digoxin from a natural extract

CoI: Digoxin

Goal: Isolation

In the realm of pharmaceutical research, our feasibility study endeavors to revolutionize the isolation process of digoxin. Digoxin is a potent cardiac glycoside utilized in the treatment of various heart conditions. It is isolated from the fermented foliage of foxglove (Digitalis lanata), however, it is often surrounded by compounds of similar structure, making isolation in its pure form challenging. Notably, digoxin’s mono- and bisdigitoxosides, alongside digoxigenin and gitoxin, represent the main impurities requiring remediation. Traditional purification methods are often laborious and inefficient, necessitating multiple steps for isolation.

However, our study introduces a novel approach utilizing centrifugal partition chromatography (CPC) to remediate digoxin from its impurities and to streamline the purification process. Through meticulous experimentation, we have identified a chlorinated solvent system tailored for the efficient separation of digoxin directly from the crude extract. With a throughput of 1 g/h, our method showcases the capability to produce digoxin with a purity exceeding 98%. Furthermore, boasting a recovery rate of 98%, our approach ensures high yield while maintaining exceptional purity. This pioneering method not only enhances the efficiency of digoxin isolation but also underscores the transformative potential of CPC technology in revolutionizing pharmaceutical production processes on an industrial scale.

Preparative separation of diastereomers

CoI: Benzopyrene compound

Goal: Separation

Our feasibility study aims to streamline the separation process of benzopyrenes, vital precursors for ß1 receptor blocker drugs, which exhibit distinct pharmacodynamic properties despite structural similarities as diastereomers. Benzopyrenes represent a pivotal component in the synthesis of these drugs, necessitating their isolation in high purity. Our sample comprises approximately 57% of isomer A and 31% of isomer B, highlighting the need for efficient separation methods. Traditional purification techniques often fall short in effectively isolating these diastereomers.

However, our study introduces a novel approach utilizing centrifugal partition chromatography (CPC) to overcome these challenges. Through meticulous experimentation, we have identified an N-hexane/methanol/water solvent system, optimized for the efficient separation of benzopyrene isomers. With a throughput of 14.4 g/h, our method showcases the capability to produce isomer A and B with remarkable purities of 99% and 99.9%, respectively. Furthermore, boasting recovery rates of 95% and 90% for isomer A and B, respectively, our approach ensures high yield while maintaining exceptional purity. This pioneering method not only enhances the efficiency of benzopyrene separation but also underscores the transformative potential of CPC technology in addressing enantiomer practice problems and chiral separation challenges.

Isolation of 10 DAB-III

CoI: 10 DAB-III from Taxus baccata extract.

Goal: Isolation

Our feasibility study endeavors to streamline the isolation process of 10-DAB III (10-Deacetylbaccatin III), a crucial precursor for the synthesis of Docetaxel, a taxane diterpenoid widely used as a chemotherapeutic agent. Extracted from Taxus baccata, 10-DAB III serves as the starting material for the semi-synthetic production of Docetaxel. However, the crude extract often contains a significant amount of co-extractives alongside the target taxanes, necessitating a purification step to remove them.

Our study introduces a novel approach utilizing centrifugal partition chromatography (CPC) to address this challenge effectively. Through meticulous experimentation, we have identified a ketone-based solvent system optimized for the efficient separation of 10-DAB III from co-extractives. With a throughput of 2 g/h, our method showcases the capability to produce 10-DAB III with a remarkable purity of 99%. Furthermore, boasting a recovery rate of 95%, our approach ensures high yield while maintaining exceptional purity. This pioneering method not only enhances the efficiency of 10-DAB III isolation but also underscores the transformative potential of CPC technology in revolutionizing pharmaceutical production processes on an industrial scale, offering an efficient and cost-effective solution for large-scale purification.

Isolation of an antibiotic Oligopeptide

CoI: Cyclosporine A (CsA)

Goal: Purification

Dive into the realm of pharmaceutical innovation with our groundbreaking feasibility study, focused on the production of pure Cyclosporin A. This cyclic oligopeptide, renowned for its immunosuppressive properties, is primarily synthesized through fermentation. However, the fermentation process often yields a mixture of products with closely related structural properties. Traditionally, purification of Cyclosporin A involved labor-intensive methods such as crystallization and preparative HPLC.

To streamline this process and eliminate costly two-step purification methods, RotaChrom developed a revolutionary centrifugal partition chromatography (CPC) solution. Our study demonstrates the transformative potential of CPC in pharmaceutical industries by efficiently isolating Cyclosporin A in just 15 minutes on an industrial scale. Utilizing an alkane-based solvent system, we achieved an impressive throughput of 22.4 g/h, yielding Cyclosporin A with a purity of 99% and a recovery rate between 70-90%. This feasibility study, conducted on an rCPC device, underscores the pivotal role of CPC technology in enhancing the efficiency and scalability of pharmaceutical production processes.

Polishing of an anticancer API

API: Anastrozole

Goal: Polishing the API

Embark on a journey of pharmaceutical advancement with our pioneering feasibility study aimed at producing pure Anastrozole, a potent anticancer agent renowned for its selective nonsteroidal aromatase inhibition properties. Anastrozole plays a pivotal role in oncology, where stringent guidelines mandate impurities to be maintained below set limits. Our study sought to streamline the purification process by replacing a labor-intensive step requiring column chromatography.

Through innovative research, we identified an ethereal-based solvent system, revolutionizing the purification process. With the throughput of 1 g/h, we achieved Anastrozole purity exceeding 99% in a single step, with a recovery rate of 75%. This transformative approach, utilizing centrifugal partition chromatography (CPC) on our rCPC device, highlights the potential of CPC technology in pharmaceutical industries. Furthermore, post-CPC purification, purity levels exceeding 99.9% can be attained in a single crystallization step. This proven applicability and seamless scalability of CPC technology move forward the efficiency of anastrozole production in industrial-scale production.

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