ColoPulse tablets in inflammatory bowel disease: Formulation, potential application and evaluation

A few years ago the department Clinical Pharmacy and Pharmacology of the UMCG and the department Pharmaceutical Technology and Biopharmacy of the RUG developed the patented ColoPulse coating. ColoPulse tablets exhibit a site-specific release in the lower gastrointestinal tract. They have the potential to improve efficacy and to minimize side effects of locally acting drugs. Moreover, oral administration is considered more patient friendly than parenteral administration. In the literature colon-specific oral delivery is considered an alternative for parenteral administration of macromolecular and peptide drugs due to the relatively neutral pH of the ileo-colonic region combined with relatively low proteolytic activity. Patients that could profit from the ColoPulse technology are patients with inflammatory bowel disease. One of the cornerstones in their treatment is parenteral administration of the monoclonal antibody infliximab. The main concerns herewith are the development of anti-drug-antibodies which are associated with a shorter duration of response and an increased risk of infusion reactions. To overcome this problem and the drawbacks of parenteral administration, developing an oral dosage form of infliximab may become a new strategy in the treatment of inflammatory bowel disease. In this thesis several studies are described, all aimed to improve the treatment of patients with inflammatory bowel disease. We focused on pharmaceutical aspects regarding formulation of ColoPulse tablets and especially ColoPulse infliximab tablets. The pharmacokinetics of infliximab were explored in an outpatient setting. This was combined with the collection of more knowledge about in vivo behavior of ColoPulse tablets in healthy volunteers and in Crohn’s patients.