Development of methods for the effective delivery of drugs to treat gastrointestinal tract diseases

UCL research is leading to improved treatments for ulcerative colitis and other conditions, through increased knowledge of the gastrointestinal tract. Improved understanding of in vivo drug release and uptake has allowed development of three patent-protected technologies for improved drug delivery.

Research led by Professor Abdul Basit (UCL School of Pharmacy) centres on understanding the chemistry and physiology of the digestive tract in relation to delivery and uptake of drugs through the oral route - by far the most common means to introduce drugs into the body. UCL researchers have identified and studied numerous intestinal parameters that can influence drug behaviour in the gastrointestinal tract, including intestinal pH, fluid volumes and composition, intestinal transit times and microbiota. These characteristics can be highly variable between individuals and within the same individual tested on different days.

UCL's work on gut physiology provides evidence that facilitates the performance, understanding and hence improvement of pharmaceutical products. For drugs that would otherwise be inactivated in the stomach, the UCL team have developed two novel technologies that exit the stomach rapidly and thereafter release rapidly. ProReleaseTM is designed to allow rapid transit through the stomach (via control of size) followed by immediate release at higher pH. Drugs incorporated into ProReleaseTM are released much more rapidly in the intestine than standard drug formulations. In 2009, this technology was licensed into Kuecept Limited, which was initially set up as a spin-out from the UCL School of Pharmacy. The company currently has an annual turnover in excess of £1 million, having worked on over 600 client projects since incorporation.

DuoCoatTM, a multiple-layer enteric coating technology, dissolves at a faster rate than industry-standard enteric coatings, due to UCL findings that the pH is lower in the proximal intestine than is commonly believed. In 2007, a patent was filled in collaboration with Evonik Industries.

Enteric-coated products are also used to deliver drugs to the large intestine or colon for the treatment of diseases including ulcerative colitis (a form of inflammatory bowel disease). However, UCL studies showed that such coated tablets or pellets often fail to release in the colon. Observed variability in drug release using conventional carriers has led UCL researchers to develop new technologies with more reliable release characteristics. For example, UCL research into alternative means to achieve colonic release of drugs led to the development of PHLORALTM, which exploits both the pH change and increase in bacterial numbers along the gastrointestinal tract, with each component acting as a failsafe to guarantee reliable and consistent targeted delivery.

The coating allows precise and consistent release of material in the colon, and may be used for the treatment of localised as well as systemic diseases. In particular, a licence has been granted to Tillotts Pharma AG for treatment of ulcerative colitis. Tillotts Pharma AG produce the market-leading product for treatment of ulcerative colitis which affects 120,000 people in the UK. Without successful drug delivery, surgical removal of parts of the intestine can be the only remaining option, and 25-40% of sufferers currently have all or part of their colon removed. This can also necessitate the use of stoma bags. The PHLORAL^TM product has entered a phase III clinical trial.

This family of products has thus had a significant impact on the development of formulations within the pharmaceutical industry, providing a clear route to much greater impact should the products be marketed for patient use. Companies have invested heavily in the development of products relating to these technologies and, in a competitive environment, have included these products in the development of their business strategies. In total, about 15 pharmaceutical companies have accessed the technologies either through licensing, options or contracts to date.