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
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
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.
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.
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
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.