New technology promises to help drug makers go green

Production of a single kilogram of pharmaceuticals often yields hundreds of kilograms of chemical waste.

Now, new chemistry developed by scientists at the University of Wisconsin–Madison, combined with technology developed by researchers from Eli Lilly and Company, promises to dramatically reduce that waste stream for a key step in the pharmaceutical production process.

Writing in the current (June 16, 2010) online edition of the journal Green Chemistry, a team led by Shannon S. Stahl, a UW–Madison chemistry professor, describes a pharmaceutical reactor technology and companion chemistry capable of using oxygen from air in safe, clean, industrial-scale production of drugs.

“A series of elaborate steps are needed to transform simple chemical feedstocks into complex drug molecules, and this process often generates a substantial amount of waste. Pharmaceutical production is often cited as one of the most wasteful sectors in the chemical industry,” says Stahl, an expert on oxidation and catalysis, processes crucial to pharmaceutical manufacture. “The hope is this new technology will contribute to the greening of the pharmaceutical industry. And reducing waste not only yields environmental dividends, but also ultimately saves companies money.”

The catch for using oxygen as a green chemical in making drugs, explains Stahl, has always been safety. The primary feedstocks for most pharmaceuticals and other industrial chemicals are hydrocarbons that have the potential to explode when combined with oxygen.

“While most drug companies recognize the potential of using oxygen as a way to reduce waste, they’ve been reluctant to consider it because of safety concerns,” notes Stahl.

Approximately two years ago, however, scientists and engineers from Lilly reached out to Stahl’s Wisconsin group to develop a continuous-flow process capable of harnessing diluted oxygen in key production steps to make the complex molecules that are the stuff of modern pharmaceuticals.

The new reactor technology works by precisely and safely blending hydrocarbons with oxygen diluted with nitrogen for the oxidation reactions necessary to make drugs and their chemical precursors. The technology is inexpensive and promises to dramatically reduce waste associated with key steps in pharmaceutical production, Stahl contends.

“Selective oxidation involves converting these hydrocarbon products and other chemical precursors into the building blocks of pharmaceuticals,” says Stahl, whose group over the last decade has been developing new aerobic oxidation methods that could be used in the manufacture of drugs.

A feature of the new reactor technology that will be attractive to companies, says Stahl, is that it has a small footprint and is a good match with the always-changing production realities of the pharmaceutical industry. What’s more, Stahl says, it has been developed to the point that it can work at the scales necessary for commercial drug production.

“It’s a very transportable technology,” says the Wisconsin chemist. “In principle, any company can now consider aerobic oxidation as part of their synthesis portfolio. This could be scaled to levels of tons per year without significant modifications to the reactor design.”

The companion chemistry for the new reactor technology was honed this year with the help of a stimulus grant provided by the National Institutes of Health. The project recently expanded to include chemical engineers at UW–Madison, who are now improving the technology to facilitate its application to industry.