Clever catalysts promise commercial advantage
08 October 2008
James Mitchell Crow/Frankfurt, Germany
Smarter catalysts that could help the chemical industry to cut costs and beat ever-more stringent government regulations were showcased at CPhI, the pharmaceutical ingredient trade show, held in Frankfurt, Germany, 30 September to 2 October.
Staying one step ahead of cheaper drug manufacturers in India and China was an important consideration for Japanese firm Sumitomo Chemical.
Their asymmetric catalysts include the phosphorus and nitrogen-based PINAP ligands, developed with Erick Carreira at ETH Zurich in Switzerland, and a series of organocatalysts developed with Yoshiji Takemoto at Kyoto University in Japan.
'If normal technology can give an intermediate in 10 steps, but our catalysts can cut this to two or three, or improves enantioselectivity, this helps us to compete with low labour costs,' Sumitomo's team leader of pharmaceuticals research, Kazuo Murakami, told Chemistry World.
- Kazuo Murakami
Meanwhile, tighter government controls on industry's use of lead have left the chemical industry searching for alternatives. Germany's BASF unveiled palladium-nanoparticle based catalysts to replace the Lindlar catalyst, a mixture of palladium and lead used to selectively hydrogenate alkynes into cis alkenes. The high surface area of the replacement palladium nanoparticles means only around 0.5 weight per cent of the metal is used, 10 times less than the traditional Lindlar catalyst.
Hans Donkervoort, BASF's production and technology manager of its speciality and fine chemicals catalysts, says avoiding lead should broaden industry's application of the reaction.
The catalyst is the first member of a new family of catalysts produced by depositing a colloid of nanoscale metal particles onto a carbon or titanium silicate support. BASF is looking to implement the technology for a number of metals, catalysing a variety of reactions.
Another traditional hydrogenation catalyst getting a modern makeover is Raney nickel, difficult to work with as it can spontaneously ignite in air. UK catalyst company Reaxa have now developed an encapsulated version of the catalyst, by trapping the metal within a polymer bead.
Once it's encased, the metal is less flammable and more easily handled, senior R&D manager David Evans told Chemistry World. Encapsulated catalysts are also easy to remove at the end of a reaction, by simple filtration; alternatively, they can be packed into cartridges and used in the flow reaction systems increasingly being adopted by pharma.
Biocatalysis also featured at the show, and was the technology behind Norwegian firm Novozyme's hyaluronic acid (HA) production, which won the CPhI innovation award. Hyaluronic acid is a natural polysaccharide that has a number of applications, thanks to its elastic and water retention properties. As well as various medical applications, the compound's use is booming as a cosmetic dermal filler to reduce wrinkles. Novozyme have engineered a non-pathogenic bacterium, Bacillus subtilis, to produce the polysaccharide.
Unlike other sources of HA, Novozyme's approach doesn't use any animal-derived raw materials - a fact which helps marketing in the cosmetics sector, says science manager Fanny Longin. The company is currently building a pharmaceutical quality (cGMP) HA facility, to be completed by 2011. The compound could be used in drug delivery, to help drug uptake in the skin or to target cancer cells, says Longin.
At the end of the API (active pharmaceutical ingredient) production pathway, companies typically use crystallisation to give the final product as a pure powder. UK company Prosonix have commercialised the use of ultrasound as a way to control crystallisation - the firm's sonocrystallisation technology recently bought by Pfizer for its manufacturing facilities in Ireland. The acoustic pressure waves causes cavitation bubbles to form and then collapse, causing transient temperatures and pressures estimated to reach 5000°K and 2000 atmospheres, explains chief technical officer Graham Ruecroft. This can trigger crystal nucleation at lower concentrations, potentially giving an extra level of control over crystal size, shape and purity.
'Sonocrystalisation technology offers an additional tool to augment existing techniques for API crystallisation and in situ selection of specific API physical characteristics,' said Pfizer global manufacturing new product team leader Simon Davidson.
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