Page 20 - CW E-Magazine (Oct-Nov-2023)

Flow Chemistry

produce using traditional batch meth- in carrying out exothermic reactions or A few challenges in its practice are
ods. Some notable examples of flow temperature-sensitive reactions in a far given separately towards the end of this
chemistry include the synthesis of vari- better manner in continuous flow mode article.
ous antiviral drugs, anti-inflammatory by even applying the desired tempera-
drugs (e.g., naproxen), the antimalarial ture profile along the reactor length. Necessity & urgency
drug artemisinin, and some of the most
expensive drugs (e.g., Ivacaftor). Be- A few more advantages of flow An international outlook
sides, the production of fine chemicals chemistry include: For the fine and specialty chemicals
and materials where synthesis time has * Safety: CFS using compact flow industry in the Europe and Japan, the
been reduced to few minutes from sev- reactors as well as CSTRs in series concept of microreactors was getting
eral hours in batch or semi-batch mode is inherently safer than batch reac- popular in early 2000 with very large
are also being realized at various scales. tions because of the small reacting efforts from IMM (Mainz) and Japanese
inventory in the reactor at any point consortium on microreactor technol-
A few reaction features where flow of time. It can also reduce the risk of ogy. Even now, while the world of flow
chemistry is the best approach include: thermal runaways and explosions. synthesis has moved from concept to
(i) moderate to highly exothermic reac- * Scalability: Continuous flow reac- reality at large scale production, the fa-
tions; (ii) reactions that are done at very tors are scale-up using the num- cilitation has largely happened through
low temperatures for very long time; bering-up strategy; however, it also efforts by various consortia across the
(iii) reactions that need to be performed poses a challenge of uniform flow world, along with a few private players.
at very high temperature in a very short distribution in a large number of Some such ongoing efforts include:
time (e.g.., pyrolysis); (iv) reactions parallel reactors, which has multi- * CC Flow consortium in Austria
involving highly reactive chemicals; ple solutions known at this moment. (University of Graz) and industrial
(v) selectivity sensitive reactions, etc. Numbering-up approach helps in partners;
Typical reactions that fall in these cat- ensuring laboratory scale condi- * Continuity Pharma (portable units
egories include aromatic nitration, hy- tions in a single reactor are retained for continuous synthesis and puri-
drogenation, oxidation, chlorination, even at large scale in each parallel fication by extraction, with a final
fluorination, ethoxylation, amidation, reactor, which allows identical per- polishing step by batch crystalliza-
ammoxidation, pyrolysis, sulfonation, formance at different scales. tion);
diazotization, polymerization, cyana- * Faster reactions: Large heat trans- * SRI International (SynFini platform
tion, lithiation, reactions involving or- fer area per unit volume, excellent and ProSyn digital twin tool and on
ganic peroxides, etc. mass transfer and mixing rates al- scaling up to a modular platform);
low the reactions to be carried out * Virginia Commonwealth Univer-
Advantages of moving into CFS at very different conditions than a sity’s Medicines for All Institute
Depending on specific type of reac- batch operation, primarily reducing (M4ALL);
tions, CFS has more advantages over the reaction rate significantly. * Phlow Corporation (continuous
the conventional batch process. For * Enhanced control: Flow chemistry processes for US-based manufac-
development of new molecules, as well allows for more precise control of turing of essential medicines);
as formulations, it is more convenient reaction parameters, such as tem- * Pfizer’s PCMM [Portable, Continu-
to screen the reagents, solvent, and ad- perature and pressure, which can ous, Miniature, and Modular] sys-
ditives in batch. Simple small volume improve reaction selectivity and tem;
flow-reactors can be used for doing yield. * Novartis-MIT Center for Continu-
these studies simultaneously using high * Minimal waste: For the selectivity- ous Manufacturing;
throughput systems. The reactions in- sensitive reactions, CFS facilitates * Continuous Pharmaceuticals (Inte-
volving multiphasic systems are often producing minimal waste because grated Continuous Manufacturing
limited by mass transfer and compact the reactions can be optimized to (ICM) technology) Mobile Pharma-
flow reactors can offer at least 10 to produce the desired product with ceuticals (MoP) plant;
100 times higher mass transfer coeffi- maximum selectivity, which re- * Center for Regulatory Aspects for
cient than a typical batch reactor; over duces the formation of unwanted Continuous Manufacturing, Univer-
50 to 500 times higher heat transfer by-products, provided the choice of sity of Maryland; and
area per unit volume; and can with- reactor is correct. In general, such * Biological Medicines on-Demand
stand extreme conditions. This helps plants are more modular. (Bio-MOD platform).

16 Chemical Weekly October / November 2023