title: Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.
abstract: BACKGROUND
  Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions.
  
  
  METHODS
  Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively.
  
  
  RESULTS
  Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h.
  
  
  CONCLUSIONS
  5-Aminosalicylic acid release profiles were variable among various commercially available formulations.
  
  
  BACKGROUND
  Shire Development LLC.
authors.affiliation: Shire, Wayne, PA, USA, aabinusawa@shire.com.
authors.forename: Adeyinka
authors.initials: A
authors.lastname: Abinusawa
authors.forename: Srini
authors.initials: S
authors.lastname: Tenjarla
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D003093:Colitis, Ulcerative / Q000188:drug therapy; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D019804:Mesalamine / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine