MODIFIED RELEASE ORAL COMPOSITION COMPRISING BIOAVAILABLE 5-ASA FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES

摘要

A modufied release oral composition for the treatment of inflammatory bowel diseases, said composition ensuring bioavailability of 5-aminosalicylic acid (5-ASA) in both the small and large intestine, and consisting of individually coated granules, each granule comprising: a core consisting essentially of 5-aminosalicylic acid (5-ASA) or a pharmaceutically acceptable salt or ester thereof and a physiologically acceptable spheronization aid, preferably a cellulose derivative, in particular microcrystalline cellulose, and a coating confining said core, said coating comprising a rate- limiting barrier-material, preferably a semi-permeable polymer, in particular ethylcellulose; and the majority of the granules, preferably more than 80%, more preferably more than 90%, of the granules being essentially spherical as defined by an aspect ratio (defined as the ratio of the length divided by the breadth) within 1.00-1.25, preferably within 1.00-1.20, more preferably within 1.00-1.15; and the majority of the granules, preferably more than 70%, more preferably more than 90%, of the individual granules of the composition exerting sieve values in the range of O0.5 mm and l 1.4, mm, preferably in the rang of O0.7 mm and o1.1; and the composition exerting the following in vitro dissolution rates [when measured in a model sytem using simulated intestinal fluid in USP Paddle System 2 operated at 37oC with stirring speed 100 rpm]: (a) within 2-20%, preferably within 5-15%, of the total 5-ASA is released after 15 minutes in the model system; (b) within 20-50%, preferably within 25-45%, of the total 5-ASA is released after 60 minutes in the model system; (c) within 30-70%, preferably within 40-60% of the total 5-ASA is released after 90 minutes in the model system; (d) within 50-90%, preferably within 55-80%, of the total 5-ASA is released after 150 minutes in the model system; (e) within 75-100% of the total 5-ASA is released after 240 minutes in the model system. 4352 ח' באדר ב' התשס" ג - March 12, 2003