Distal ileum and colon: targeted sites for 5-ASA release

Sulphasalazine, used in the treatment of ulcerative colitis, is cleaved in the colon by the metabolic action of colonic bacteria on the diazo bond to release 5-Aminosalicylic acid (5-ASA) and sulpharidine. Whilst the former has been demonstrated to be active moiety, the latter is reputed to be responsible for toxicity associated with sulphasalazine therapy. A new multi-particulate formulation of 5-ASA has been designed (Asalan) to achieve targeted release of the drug in both the distal small intestine and colon and hence may be beneficial in the treatment of not only Ulcerative Colitis but also Crohn's disease. An imaging study was performed with beads formulated with barium sulphate using the same procedure employed to prepare 5-ASA beads. This study suggested 5-ASA capsule disintegration and bead dispersal in both the distal ileum and colon. This targetting was confirmed in two further in vivo studies using the 5-ASA formulation itself. In the first study comparison of plasma ASA levels following treatment with sulphasalazine treatment confirmed that 5-ASA release was occurring proximal to the colon. Despite this earlier release, the percentage of administered dose that was unabsorbed (dose-urinary recovery) was approximately 90%. In a second study a comparison was made with a single unit tablet of 5-ASA. A greater consistency and accuracy of targetting, as revealed by the appearance of plasma ASA levels, was confirmed for the capsule formulation. These separate studies were undertaken to evaluate the in vivo intestinal release characteristics of this new 5-ASA formulation in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)