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* = Presenting author

P302 Pharmacoszintigraphic investigations of a high-dose mesalazine tablet with a new coating

G. Nicholas1, M. Nagy1, R. Hofmann*2, D. Wild1, M. Haschke3

1University of Basle, Nuclear Medizine, Basle, Switzerland, 2Tillotts Pharma, Medical Affairs, Rheinfelden, Switzerland, 3University Hospital , Clinical Pharmacology & Toxicology, Basle, Switzerland

Background

Mesalazine has been used for several decades for induction of remission and maintenance of remission of mild to moderate ulcerative colitis (UC). Doses recommended for induction and maintenance of remission require several gastro-resistant tablets to be taken each day. Commonly used are polymer coatings, which disintegrate in a pH dependent manner (pH ≥ 7). The tested formulation (TP05) uses a double trigger, double layer coating technology: an outer polysaccharide and polymer coating, whose degradation is triggered by either ph or intestinal bacterial enzymes and an inner layer for faster dissolution of the active constituent at the ileo-caecal target region. We investigated the influence of this novel formulation on the delay and site of release of Mesalazine.

Methods

Design: Open-label, single-center study.

Number of participants using a specific formulation of TP05: 9 (3 patients, 6 healthy volunteers).

Inclusion: Healthy subjects or patients with mildly active UC, between 18 and 55 years old.

Test product, dose and mode of administration: A single dose TP05 tablet containing 1600 mg mesalazine with double layer coating radiolabelled with 1 MBq Sm-153 was administered orally.

Duration of treatment: 1 single tablet was administered in the morning (fasted condition).

Repeated gamma-scintigraphy pictures were taken to determine the anatomical site of initial tablet disintegration (ITD) and the release of the study drug.

In parallel blood samples were collected for a PK profile (data not shown).

Results

The anatomical site of ITD was determined to be within the ileocaecal junction (ICJ) or ascending colon (AC) in 8 out of 9 participants. One was in the transverse colon (TC). The location of complete tablet disintegration (CTD) is also within the right colon in 89% of subject/patients.

For all subjects combined, the median gastric rention time (Q1, Q3) (min) that was 30 (30, 30) and the small intestine transit time (SITT) was 150 (120, 210).

The median (Q1, Q3) colonic arrival time of TP05 occurred after 270 (240, 360) minutes and ileocaecal junction residence time was 30 (30, 60) minutes.

Initial and complete tablet disintegration occured 270 (240, 450) and 400 (270, 600) minutes (median, Q1, Q3) post-dosing.

No serious adverse events occurred.

Conclusion

The scintigraphic Results demonstrate that this new coating technology allows reliable delivery of mesalazine from a high-dose mesalazine tablet in fasted subjects to the site in which it is most needed for a maximal therapeutic effect.

TP05 was found to be well-tolerated.