title: A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis.
abstract: The aim of the present study was to develop a multi-unit dosage form containing 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC), optimised on the basis of recent studies indicating that UC patients have higher intestinal pH than was previously thought to be the case. Pellets with a drug content of 77.4% were prepared by a granulation and spheronization process and then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit((R)) FS 30D) to achieve site specific drug release close to the ileocecal valve. Dissolution tests were carried out in a paddle dissolution apparatus in media simulating pH conditions at various locations in the gastrointestinal tract. The pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release was found to be zero order, while at pH 6.5 and below no release occurred. In a biorelevant medium which simulates the fasting proximal small intestine fluid it was shown that neither surfactants (sodium taurocholate and lecithin) nor changes in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the well established Eudragit((R)) S, and to currently marketed products licensed for the treatment of UC, the multi-unit dosage form coated with the new polymer exhibited an in vitro dissolution profile more appropriate to the pH profile of the ileum and the colon observed in UC patients.
authors.affiliation: Department of Pharmaceutical Technology, Johann Wolfgang Goethe University, 60439, Frankfurt, Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Rudolph
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.forename: T E
authors.initials: TE
authors.lastname: Beckert
authors.forename: H
authors.initials: H
authors.lastname: Petereit
authors.forename: J B
authors.initials: JB
authors.lastname: Dressman
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism*; D004343:Drug Implants / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019804:Mesalamine / Q000737:chemistry* / Q000627:therapeutic use; D008689:Methacrylates / Q000737:chemistry; D020366:Methylmethacrylate / Q000737:chemistry; D009994:Osmolar Concentration; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004343:Drug Implants; D008689:Methacrylates; D013501:Surface-Active Agents; D020366:Methylmethacrylate; C008384:methacrylic acid; D019804:Mesalamine; C035956:methyl acrylate