Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels

INTRODUCTION: 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. CONCLUSION: 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. FUNDING: Shire Development LLC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-015-0206-4) contains supplementary material, which is available to authorized users.