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Medicine and Health

Delivering drugs right on target

   
 
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A specialist company in Nottingham, together with Belgian and Italian partners, is developing a new type of coating for pills which could make injections a thing of the past for the sufferers of many diseases.
The coating uses a newly-synthesised polymer which can survive the journey through the digestive tract, breaking down only once it reaches the colon. The addition of an absorption enhancer, which causes the cell wall in the colon to let the drug pass through more easily, could allow vital drugs such as insulin to be delivered by mouth instead of injection.


Nobody likes having injections - particularly people suffering from long-term illnesses which require repeated medication. It's much less distressing to take a pill. But the acids and enzymes found in the stomach and intestines will attack pills just as they attack the food we eat, and if a drug is not released in the right place at the right dosage, great harm can result.
The pharmaceutical industry has therefore long been searching for the right sort of coating for pills which can survive the passage through the digestive system all the way to the colon, because it is often in the colon that drugs can most easily be absorbed; hence, this project, coordinated by DanBioSyst UK Ltd, a specialist company based close to Nottingham University in England. They were primarily interested in finding better ways of treating bowel diseases and in developing new ways of delivering peptide and protein drugs by mouth. A growing list for such drugs being discovered by the biotechnology industry is driving demand for this technology.
The company knew that Gent University (Belgium) was a leader in synthesising new medical polymers, so they teamed up with them and with Pharmatec in Milan, a company which has expertise in taking medicines from trial batch to production scale.

Finding the weak link

To develop the coating, the partners needed to find a polymer that would break up in the colon, but not in other parts of the gut. Their starting point was that the colon is full of anaerobic bacteria, which create an oxygen-free, reducing environment.
They then searched for a polymer with a 'weak link' in its chain - such as an azo or a disulphide bond - which these bacteria could easily attack. Gent University synthesised a number of different types of polymer, and tested them for their physical strength and how they behaved in the conditions found in the colon. The most promising candidates were then sprayed onto pills and tested again.
The polymer finally selected for development is of the disulphide type, and its safety was first tested in rats. Following these tests two batches of tablets were prepared with different coating thicknesses, labelled with a radioactive marker and administered to human volunteers. The disintegration of the coatings in the colon was tracked using a gamma camera. The results were good - the majority of the pills with the thinner coating dissolved where they were supposed to, in the colon.

Faster absorption

Alongside this, the researchers wanted to find a way of increasing the amount of peptide and protein drug absorbed from the colon. They screened a number of absorption enhancers and tested the most promising one first on pigs, which have digestive systems very similar to human ones, and then on humans.
While the partners would have liked to test this in combination with the new polymer coating they were developing, they didn't think that they would have the new coatings ready in time. Therefore they developed, tested and used a more conventional coating, using off-the-shelf 'enteric' polymers which don't dissolve in the acid of the stomach but slowly dissolve in the intestines. As it turned out, they made such good progress that they probably could have combined the two technologies. Nevertheless, they now have two results for the price of one, as the improved conventional coating will prove very worthwhile in its own right.
Because of the long lag-time needed between testing the new polymer coating and moving to full-scale production, the project team made use of Pharmatec's expertise by developing a third element to the project: an improved way of delivering a drug known as 5-ASA (5-aminosalicylic acid) to the colon in the form of small pellets. 5-ASA is useful in treating inflammation of the bowel, and the new type of pellet has been shown to be an improvement on existing ways of administering it, bringing the promise of more effective treatments for diseases such as ulcerative colitis and Crohn's disease.

Investment needed

Ironically, it is the project's most exciting technological development that is proving the most difficult to take forward. The development of the disulphide polymer coating is a unique piece of work, the first time this type of polymer has been synthesised for this application.
However, it is a big undertaking to bring it to market, requiring a considerable amount of capital in order to scale up production, do larger-scale safety tests and go into volume production. DanBioSyst has not yet found a partner able to make the necessary investment. If and when it does, commercialisation will probably take about five years.
The further development of the other technologies, in contrast, looks likely to take place more rapidly. DanBioSyst is already exploring the possibilities of the absorption enhancer with new partners, and the 5-ASA pellet system has successfully completed its first clinical trial. The enhancer and the pelleting system could be on the market within two years.

 

Project Title:  
Polymeric systems for selective
delivery to the large bowel

Programmes:
Industrial and Materials Technologies (BRITE-EURAM/CRAFT/SMT)

Contract Reference: BE-4055   

Cordis DatabaseFor more information on this project,
go to the CORDIS Database Record

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