Delayed‐release mesalazine (5‐aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

Abstract

Medicine and Dentistry, London and 2Leigh Infirmary, Leigh 1 Delayed-release mesalazine has been formulated to deliver 5-aminosalicylic acid to the colon. We have therefore studied the ileostomy excretion and coat dissolution of this preparation. 2 Following ingestion of a single tablet 88% (range 69-114%) of the 400 mg dose appeared unchanged in the ileosomy effluent over the subsequent 12 h. 3 Ileostomy effluent pH appeared to be a major determinant of 5-aminosalicylic acid release. 4 In vitro studies revealed rapid coat dissolution above pH 7.0, slow dissolution between pH 6.0 and 7.0 and non-dissolution at pH 2.0 and 4.0.

Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs

“…Direct evidence on pH dependent release in ulcerative colitis is not yet available but preliminary data suggest that in most patients small bowel pH, measured with a radiotelemetry capsule,12 is high enough for sufficient time to allow capsule dissolution 47. In vitro studies have shown that a low pH inhibits colonic bacterial metabolism of carbohydrate, urea, and other nitrogenous compounds21: it is possible that increased colonic acidity could also reduce azo reductase activity and release of 5-ASA from sulphasalazine, olsalazine, and balsalazide 49a…”

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“…SASP has, further, been shown to have a unique place in prophylactic treatment of inactive UC in contrast to corticosteroids (77). Thus, 2 g SASP for one year reduced clinical relapse significantly from 24/33 in the placebo-group to 6/ 34 in the SASP group, with the reservation that compliance was not perfect in the treated group (97). Later, placebo-controlled longterm-studies found the efficacy rates of SASP to be a reduction of relapse from 55% in the placebo group to 12% (35).…”

“…From the comparison of intestinal elimination of SASP and 5-ASA sustained-release formulations by Bondesen et al (111) and other observations (73,97), it is concluded that systemic kinetics alone are erroneous in predicting the regional availability from a SR-drug. Although, the systemic kinetics of SR-drugs imply low availability, regional intestinal concentrations of 5-ASA may be sufficient for local drug-effect (111).…”

“…A SRF for distal ileal release and colonic action was studied (97). Dissolution of tablet-coating was pH-dependant with a 100% in vitro release of 5-ASA within 30 minutes at pH above 7 and of 5 hours at a pH between 6.3 and 7.0, respectively (97). A mean of 6%) of dose was eliminated in the urine with a maximum of 20%, whereas ileal elimination during 12 h was 88% mostly as un-metabolized drug.…”

Prandial and diurnal effects on the absorption of orally administered enteric coated 5‐aminosalicylic acid (5‐ASA).

“…Various modified-release peroral formulations have been developed that target the dissolution of the tablets to specific sections of the gastrointestinal tract. Acrylic polymer coated tablets (Claversalg, Mesalazine®) are designed to dissolve at pH > 6 thereby making the drug topically available in the more proximal parts of the intestine (Riley et al, 1988). Normally only a small fraction of the dose is absorbed from the gastrointestinal tract.…”