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New discovery could help oral medications work faster and more efficiently

Nov. 1, 2016 - A team of researchers from the University of Minnesota and The Dow Chemical Company have discovered a new method for customizing ingredients that help oral medications dissolve in the body and be absorbed into the bloodstream. The materials discovered in this study could allow life-saving drugs to work more efficiently.

The University of Minnesota and Dow have filed a patent on the discovery that may also lower the cost to produce new medications.

The research study is now online and is published in the current issue of the American Chemical Society’s ACS Central Science, a leading journal in the chemical sciences.

One of the biggest challenges for pharmaceutical companies when developing oral medications is to ensure that the body will fully absorb the drug molecules. Many therapeutic structures do not easily dissolve on the molecular level, which means they are less effective. In that case, the dose must be increased for patients, which may increase side effects.

“A way to explain the differences in solubility of medicines is to think of how sugar easily dissolves in water and is rapidly absorbed by your digestive system, whereas sand doesn’t dissolve in water and if swallowed, would pass right through the digestive system,” said Theresa Reineke, a chemistry professor in the University of Minnesota’s College of Science and Engineering and lead researcher on the study.

Drug companies add substances, called excipients, to help the medicines dissolve in the stomach and intestinal fluid, but there have been few improvements in recent years to this decades-old technology. The process outlined in the study is a major breakthrough that revolutionizes the process of making drug structures more soluble in the body so that they are better absorbed.

Funded by Dow, researchers examined two medications—phenytoin, an anti-seizure drug, and nilutamide, a drug used to treat advanced-stage prostate cancer. The team used automated equipment at Dow to synthesize long-chain molecules. Their efficiency as excipients with these drugs were then tested with facilities at the University of Minnesota, including the Characterization Facility located in the University’s College of Science and Engineering. One particular excipient discovered by this research allowed these insoluble drugs to fully dissolve in simulated intestinal fluid in a test tube. When they tested phenytoin with the new excipient in rat models, it promoted drug absorption three times better than the previous formulation.

The research discovery is one result of a five-year collaboration between Dow and the University of Minnesota for research partnerships to develop new chemical solutions, improve research facilities, and train the next generation of scientists.

“This discovery is a perfect example of what can happen when industry and academia come together,” said Frank Bates, a Regents Professor in the University’s Department of Chemical Engineering and Materials Science and co-author of the study. “This research has yielded something that could have a huge effect on human health and lower the cost of medications.”

In addition to Reineke, Guillaudeu, and Bates, other researchers who were part of the team included current and former University of Minnesota students and post doctoral researchers Jeffrey Ting (lead author), Swapnil Tale, Anatolii A. Purchel, Seamus D. Jones, Lakmini Widanapathirana, Zachary P. Tolstyka, and former Dow researcher Li Guo.

To read the complete research study, entitled “High–throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals,” visit: http://pubs.acs.org/doi/full/10.1021/acscentsci.6b00268

Excerpts from a news release written by Rhonda Zurn, College of Science and Engineering, and Lacey Nygard, University News.

Related Link: http://z.umn.edu/medicine16

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