Chemical and Biomolecular Engineering
A Crystal Clear Solution
Researchers receive collaboration award for pharmaceutical technology.
It was a multimillion-dollar mistake. Several years back, a major pharmaceutical company had just put a new drug on the shelves after completely following a process approved by the Food and Drug Administration. But a few months after the drug was in stores, its properties began to change on the shelf in totally unexpected ways. The product was pulled, and by the time they could put the drug back in production, the ordeal had cost the company hundreds of millions of dollars.
University of Illinois researchers, working with the pharmaceutical industry, have since developed procedures that decrease the likelihood of such disasters; and as a result, they were recently awarded the 2009 Collaboration Success Award from the Council for Chemical Research.
The U of I team, led by Richard Braatz, professor of chemical and biomolecular engineering, focused on the crystallization process, one of the most challenging steps in the production of pharmaceuticals. As Braatz explains, most drugs are sold in a crystallized form because it tends to be the most stable and cheapest method for drug delivery. Essentially, a tablet consists of drug crystals and other ingredients compacted into the shape of a pill.
During the crystallization process, impurities are removed; however, the process is very sensitive to many factors and can be affected by small amounts of contaminants. Also, when a drug’s production is scaled up, the crystals can be affected if the mixing is not done ideally during processing.
Braatz, along with a team of eight students and postdocs, worked with Merck and Co. researchers to design a set of procedures and statistical methods that made it possible to get very high accuracy in analyzing crystallization processes using real-time, in-process infrared spectroscopy and laser-based, particle-sizing sensor technology. This information was then used to design and control processes for manufacturing crystals with the desired properties.
“The technology helps you get the right purity, the right crystal structure, and the right particle size distribution,” Braatz says.
In fact, their technology was so successful with Merck that several other companies quickly came on board. The FDA now recognizes it as state-of-the-art technology. Braatz’s work with Merck has since concluded, but he continues to refine the process technologies in collaboration with a consortium of pharmaceutical companies.
As for the multimillion-dollar mistake, Braatz says it never would have happened if the company had fully understood the chemistry of their system.
“Our technology makes the crystallization process purer, safer, and faster,” he says.