Research conducted in Groningen has yielded a technique that makes it possible to have drugs delivered directly to the colon. This may lead to more effective treatment of bowel diseases such as colitis ulcerosa and Crohn’s disease, and the technique could also help to combat overweight. What’s more, drugs that now must be injected could be administered as a pill. On 23 September 2011, pharmacist Reinout Schellekens will be awarded a PhD for his research by the University of Groningen.
Medication takes many forms: pills, ointments, injections, sprays, etc. Advanced methods of administration have been developed to administer the active ingredient as directly as possible. However, some parts of the body, including the colon, are hard to reach with drugs.
Drugs administered in a tablet or capsule are usually released in the stomach and then absorbed into the bloodstream in the small intestine. As a result, they hardly manage to reach the colon. By giving the capsule or tablet a protective layer − a coating − its disintegration can be postponed until the final part of the small intestine and the beginning of the colon. Although this method is widely used, it is far from ideal. PhD candidate Reinout Schellekens: ‘You could say that having drugs released in the colon is the Holy Grail for pharmacists. It’s a goal we have now finally nearly achieved.’
There are various techniques to get drugs to survive passage through the stomach and small intestine. Some capsules only release their active ingredient after a certain period after being ingested. Other capsules do so at a certain pressure or acidity. The coating’s characteristics determine its release profile.
Schellekens has developed ColoPulse, a coating sensitive to variations in acidity that does not dissolve gradually, but breaks open suddenly. He achieved this by taking an existing coating (Eudragit S) and adding an ingredient that can swell strongly extremely quickly, thus causing the coating to disintegrate. This occurs in an environment where acidity is low, such as in the small intestine, as opposed to the extremely acidic stomach contents.
The result of the coating’s acidity-driven disintegration process is that the active ingredient is released specifically in the colon, all in one go. Schellekens: ‘Existing pills run the risk of not even dissolving at all. Our technique is more reliable; the chance that our pill will not dissolve is negligible.’
The ColoPulse technique can be used to effectively fight colonic inflammatory disorders, such as Crohn’s disease and colitis ulcerosa. But it could also be used to combat overweight, as it can be used to transport small quantities of fat directly to the last segment of the small intestine. As soon as the undigested fat is released there, the intestines signal that the digestive system is being overloaded, which in turn diminishes feelings of hunger. This could prove successful in treating overweight, in combination with a diet.
And finally, the technique also offers possibilities regarding the treatment of arthritis, cancer and diabetes. Schellekens: ‘The drugs used for these diseases are based on proteins. At the moment they need to be injected, to avoid being digested in the stomach. Perhaps patients will be able to take them as a capsule, with the drug reaching the bloodstream when it has been absorbed in the colon.’
Many of the existing drugs that are meant to release their active ingredient in the colon have not been tested on humans. Schellekens’ invention, however, has been extensively tested. It was not only tested in a mock gastrointestinal system in the laboratory, but was also tested on 19 test subjects. A number of studies using labelled substances (non-radioactive stabile isotopes) revealed that the capsules released their active ingredient with a high degree of accuracy and that this was absorbed very effectively.
Reinout Schellekens (Rotterdam, 1970) studied pharmaceutical sciences in Utrecht. He conducted his research alongside his job as hospital pharmacist at the University Medical Center Groningen (UMCG). The study was conducted at the Pharmacy Department of the Faculty of Mathematics and Natural Sciences of the University of Groningen, the UMCG Clinical Pharmacy Department, and under the auspices of research school GRIP. Schellekens is currently employed as a manager at Abbott Laboratories in Zwolle. He was supervised by Prof. Erik Frijlink and his thesis is entitled: Translational research into oral colon-specific drug delivery: from laboratory to clinic.
Reinout Schellekens, reinout.schellekens kpnplanet.nl.
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