Catalytic process improves speed and efficiency of medicines manufacture

About 70 per cent of pharmaceuticals are manufactured using palladium-driven catalytic processes, which can be fast or efficient but not at the same time.

palladium
Close-up of the microspheres at 500µm (credit: Milad Abolhasani)

Now, researchers at North Carolina State University have now developed a so-called green chemistry method that reportedly combines aspects of both processes to improve efficiency at a minimal cost of processing time.

Palladium-driven catalytic reactions are used to connect carbons in small, organic molecules to create larger molecules for use in pharmaceuticals and other applications.

Until now, there have been two ways to do this, namely with homogeneous and heterogeneous processes.

In homogeneous processes, palladium is dissolved in solution, allowing maximum exposure to the organic molecules, or reagents. This makes the process very fast, but results in a lot of palladium either being wasted (because it gets thrown out after target molecules are harvested) or being recovered at high cost (because the recovery process is expensive).

In heterogeneous processes, palladium is fixed to a hard substrate in a pack-bed reactor, and the reagents are run through the reactor, a process that takes longer but with little or no wasted palladium.

"We've created and tested a new process called pseudo-homogeneous catalysis, which combines the best of both worlds: it is nearly as fast as homogeneous catalysis, while it preserves virtually all of the palladium," said Milad Abolhasani, an assistant professor of chemical engineering at NC State and corresponding author of a paper on the work.

The new technique is said to rely on novel, elastic silicone-chemistry based microspheres developed by the research team using microfluidics.

"We used a microfluidic strategy to make elastomeric microspheres with a narrow size distribution to make them 'loadable' into a tubular reactor without clogging," Abolhasani said. "That was essential, because conventional batch scale polymerisation techniques result in elastomeric microspheres with a large size distribution that would clog the reactor when loaded."

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Each silicone microsphere is loaded with palladium. Reagents then pass through the microsphere and interact with the palladium. The resulting pharmaceutical target molecules leave the microsphere again with palladium remaining trapped in the microsphere.

"The flexible spheres allow the palladium catalyst to 'settle' inside the microreactor environment," said Jan Genzer, the S. Frank and Doris Culberson Distinguished Professor of Chemical and Biomolecular Engineering at NC State, and a co-author of the paper. "The flexibility of the silicone sphere allows the palladium catalyst to adopt very many configurations during the reaction - as is the case in homogeneous processes. The palladium catalyst is retained for further use - as is the case in heterogeneous processes."

"In proof-of-concept testing, our process was much faster than any heterogeneous techniques, but still marginally slower than conventional homogeneous processes," Abolhasani said. "We're currently working on optimising the properties of our elastic microspheres to improve the reaction yield."

According to NC State, another advantage of the pseudo-homogeneous technique is that it makes use of nontoxic solvents, such as water and ethanol. Conventional homogeneous techniques use typically organic solvents, such as toluene, which are not environmentally benign.

"It is important to demonstrate that green chemistry approaches can be used to make a process that is, in all, more efficient than existing techniques," Abolhasani said. "You do not have to trade safety for cost-effectiveness."

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