Researchers find way to clean up the drugs market

Sep 13 2004

Researchers from the University of Cambridge and the Massachusetts Institute of Technology have made a breakthrough by using supercritical carbon dioxide (scCO₂) as a reaction medium for the preparation of molecules of interest to the pharmaceutical industry.

Many industries throughout the world have begun using the non-toxic, environmentally friendly scCO₂ as a solvent, replacing harsher volatile organic solvents, such as chlorinated hydrocarbons and chlorofluorocarbons.

Until now it was not considered possible to make certain classes of molecules in CO₂ because it was thought that they would react with the CO₂.

Cambridge University’s Professor Andrew Holmes, Director of the Melville Laboratory, together with MIT’s Professors Rick Danheiser and Jefferson Tester, have changed all that by figuring out how to use scCO₂ for reactions without it reacting with the reagents.

Since the 1990s, scCO₂ has emerged as an environmentally benign substitute for more conventional solvents used for organic synthesis, such as those that enter the atmosphere from sprays and similar products. Dry cleaners, plastics manufacturers, food producers and various industries involved in the extraction of flavours and fragrances are already using the ‘benign’ solvent, resulting in more environmentally friendly industrial practices. Using scCO₂ as the extractive agent to remove caffeine selectively and leave the flavour of fresh coffee, for example, produces decaffeinated coffee beans.

Although a greenhouse gas, scCO₂ can be obtained in large quantities as a by-product of fermentation and combustion. The ready availability, coupled with its ease of removal and recycling, makes scCO₂ an exciting prospect for synthetic and industrial applications.

Supercritical carbon dioxide is a supercritical fluid, so called because it is taken beyond its critical temperature, to a point where it’s neither a liquid nor a gas but retains both liquid-like solvent properties and gas-like densities.

Pharmaceutical companies have begun using scCO₂ for processing drugs into powder consistently, but the researchers’ findings may soon mean that the entire manufacturing process can be integrated, using scCO₂ for both synthesis and processing them into powders.

Organic solvents can always react in undesired ways, so an advantage to using this non-toxic supercritical fluid is that it reduces the chances for alternative and less-desired outcomes.

Another major advantage to using supercritical fluids for organic synthesis is the ability of these physical properties to be tuned simply by a change in pressure and/or temperature.

Professor Holmes dreams of helping the pharmaceutical industry streamline the drugs manufacturing process with the techniques he and his team have developed. “We’re making molecules of interest to pharmaceutical companies — aromatic amines — which are a key fragment in many neurological drugs. Before it was considered impossible, but we’ve got preparations of aromatic amine reactions to work in supercritical carbon dioxide.”

A patent has been filed on behalf of the work done at Cambridge and MIT, which was funded by the Cambridge-MIT Institute (CMI). The researchers have published their findings in Chemical Communications, (The Royal Society of Chemistry) 2004.

In addition to the collaboration with MIT, the CMI project has enabled scientists at Cambridge to work closely with Professor Gerry Lawless and his team at the University of Sussex.

Pharmaceutical giant AstraZeneca is one of a number of companies that has long been interested and supportive of Professor Holmes’ work in scCO₂.