25-Feb-2015 - Max-Planck-Institut für Kolloid- und Grenzflächenforschung

An assembly line for medications

Efavirenz can now be produced more cost efficiently and sustainable utilizing continuous flow chemistry.

Researchers at the Max Planck Institute of Colloids and Interfaces (MPICI) and the Freie Universität Berlin have succeeded in developing better methods of producing APIs (active pharmaceutical ingredients). As a result, Efavirenz, one of the preferred agents for treating HIV in combination therapies, can now be produced using a concise continuous flow method. This process may fundamentally change the way APIs are produced.

Today, virtually all active pharmaceutical ingredients (APIs) are produced using multiple distinct processes in “batch”. This means that all ingredients react in a pot, pretty similar to the method of cooking. “Continuous flow” means the reaction takes places while the chemicals move through a “pipe” or some tubing – conceptually similar to a conveyer belt. In this way, the reactions are safer and more efficient.

Flow chemistry has fundamental advantages when compared to other methods. The target product can be produced in a faster, more cost efficient manner and, more often than not, with better product quality. The smaller amounts of chemicals reacting in flow devices don´t lead to smaller production charges. In principle this can be compared with a bucket under a dripping faucet. The bucket can be filled opening the faucet (fast), but over time constant dripping (slow) will lead to the same effect. In reality, the total time consumption leading to a similar amount of API is comparable, but in flow the reaction needs less investment and exhibits a much higher degree of control.

In addition to producing single medications such as Efavirenz continuously, a single, modular reactor can be used to produce patented and generic medicines such as lyrica, gabapentin, and baclofen – used to treat general anxiety disorder, epilepsy, and spasticity, respectively. The total value of the medications sold each year exceeds five billion Euros. These medications belonging to three different structural classes (g-amino acids, g-lactams and β-amino acids) were produced by just changing the order of reactors.

Most commodity products, including cars, are produced by using assembly lines. The Max Planck researchers demonstrate for the first time that a modular assembly line system for the production of important medications can work. Prof. Dr. Peter H. Seeberger emphasizes: “Our modular flow technology will fundamentally change the way APIs are produced. We have demonstrated that the conceptual breakthrough now yields better access to life saving drug substances such as the HIV medication Efavirenz. In a next step these processes will have to be industrialized.”

Dr. Kerry Gilmore, group leader of the “flow chemistry” team adds: “What is truly revolutionary about this approach is not the incremental advance in reactor technology, but the conceptual leap of synthesizing a range of products using a single modular setup, allowing access to multiple medicines without the need for multiple production facilities.”

For the key step of the synthesis of Efavirenz a readily available and harmless copper catalyst was used, substituting toxic chemicals such as phosgene, a chemical warfare agent.

Dr. Camille Correia, from the South American country of Guyana, the key chemist in the synthesis of the HIV medication, hopes the effort of the team will have an impact: “We were able to produce the medication in three chemical steps in less than two hours. To the best of our knowledge this is the most cost efficient and fastest method available. Unfortunately Efavirenz is often too expensive for patients in developing countries. We hope our effort helps to lower the market price for life saving drugs.”

Facts, background information, dossiers

  • MPI für Kolloid- un…
  • Freie Universität Berlin
  • active pharmaceutic…

More about MPI für Kolloid- und Grenzflächenforschung

  • News

    In milliseconds from polluted to clear water

    Researchers at the Max Planck Institute of Colloids and Interfaces developed a membrane that is composed of a bundle of nanometer-sized tubes. They used it as a nanoreactor to convert water marked with methylene blue into clear water in milliseconds using sunlight as a driver. ‘Running reac ... more

    Green Chemistry: Sustainable p-xylene production

    Lemonade, juice and mineral water often come in PET bottles. While these are practical and functional, their production is complex and not necessarily sustainable. The starting material for terephthalic acid, which is used to produce saturated polyesters such as PET (Polyethylene terephthal ... more

    Put into the right light - Reproducible and sustainable coupling reactions

    A team of researchers reports in the journal Nature Catalysis that sustainable carbon-nitrogen cross-couplings can be performed using simple nickel salts, carbon nitrides and light. The chemists study the use of cost-effective and reproducible semiconductors as photocatalysts in coupling re ... more

  • q&more articles

    With Light in the Fight against Malaria

    Malaria represents a global threat to health, which is difficult to keep under control. Amongst more than 200 million sufferers, over 500,000 die each year of the disease, with the risk of a fatal outcome being particularly high in children [1]. more

  • Authors

    Dr. Daniel Kopetzki

    born 1983, studied chemistry at the University of Regensburg and received his doctorate from the Max Planck Institute of Colloids and Interfaces in Potsdam, in the Department of Colloid Chemistry. Since Sept. 2011, he has been working as a post-doctoral fellow for Prof. Dr. Seeberger at the ... more

    Prof. Dr. Peter Seeberger

    born 1966, studied chemistry at the University of Erlangen-Nuremberg, and received his doctorate in biochemistry from the University of Colorado. After holding a post-doctorate position at the Sloan-Kettering Institute for Cancer Research in New York City, he was Assistant Professor and Fir ... more

More about Max-Planck-Gesellschaft

  • News

    Pumping up the music of molecules

    Sensitive animal noses can sniff out trace particles, such as volatile organic compounds, in the ambient air. Humans, on the other hand, are developing innovative technologies for this purpose, such as optical spectroscopy. This uses laser light to detect the molecular composition of gases. ... more

    How to find marker genes in cell clusters

    The thousands of cells in a biological sample are all different and can be analyzed individually, cell by cell. Based on their gene activity, they can be sorted into clusters. But which genes are particularly characteristic of a given cluster, i.e. what are its “marker genes”? A new statist ... more

    Cell-culture breakthrough: Advanced “mini brains” in the dish

    “Outer Radial Glia” (oRG) cells are nervous system stem cells that are instrumental for the development of the human cortex and have been challenging to produce in the lab. Now, a team of Max Planck researchers from Berlin succeeded in generating brain organoids that are enriched with these ... more

More about Freie Universität Berlin

  • News

    Directing nanoparticles straight to tumors

    Modern anticancer therapies aim to attack tumor cells while sparing healthy tissue. An interdisciplinary team of researchers at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and FU Berlin has made important progress in this area: the scientists have produced tiny nanoparticles that are design ... more

    Memory like a Sieve – Or Not?

    Humans are not only capable of forming memories but also recalling these memories years later. However, with advancing age many of us face difficulties with forming new memories, a process usually referred to as age-induced memory impairment. Developing an elaborate understanding of this pr ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: