title: A novel dissolution method relevant to intestinal release behaviour and its application in the evaluation of modified release mesalazine products.
abstract: Mesalazine (5-ASA) is a compound being used in the therapy of inflammatory bowel disease (IBD). Considering the fact that 5-ASA is locally active and that the location of inflammation in IBD may vary, it is recognized that the release profile of 5-ASA drugs is the dominant factor for adequate local bioavailability. Furthermore, it is hypothesized that systemic absorption of 5-ASA (mainly in the upper intestinal segments) increases the risk of side effects. These facts relate to the conclusion that a method determining the dissolution profile under biorelevant conditions is a valuable tool for evaluation and comparison of 5-ASA-products. We tested several commercially available products (Salofalk tablets, Salofalk granules, Asacol tablets, Pentasa tablets and granules) in a gastro-intestinal simulation system (GISS). The GISS is based on the pharmacopeial dissolution test. The release profiles of all products are in agreement with their technological concepts. The percentage of the dose released in the simulated colon is small in all products. The GISS is a robust system able to discriminate between products which apply different modified-release technologies. Colon-selectivity of modified-release 5-ASA products might further be improved. The commercially available 5-ASA containing oral dosage forms exhibit different release profiles, which suggests that the optimal product may differ per patient.
authors.affiliation: Department of Clinical Pharmacy, University Medical Center Groningen, University of Groningen, The Netherlands. R.C.A.Schellekens@apoth.umcg.nl
authors.forename: R C A
authors.initials: RC
authors.lastname: Schellekens
authors.forename: F E
authors.initials: FE
authors.lastname: Stuurman
authors.forename: F H J
authors.initials: FH
authors.lastname: van der Weert
authors.forename: J G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: H W
authors.initials: HW
authors.lastname: Frijlink
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D019804:Mesalamine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008954:Models, Biological; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D019804:Mesalamine