Design and Optimization of High-dose Colon-targeted Controlled Drug Delivery System for Mesalamine using Eudragit Coated Matrix Tablets

Abstract

Mesalamine (5-aminosalicylic acid or 5-ASA or Mesalazine) is the first-line anti-inflammatory agent recommended for the treatment of active symptoms, induction of remission and maintenance of remission in patients with mild-to-moderate ulcerative colitis [1]. Mesalamine acts topically on the colonic mucosa but when orally administered, it is extensively and rapidly absorbed in the small intestine, leading to little localization of Mesalamine in the colon and hence, low efficiency with significant systemic side effects [2].Consequently, three methods have been commonly used for targeting of Mesalamine to the colon: a pro-drug concept, enteric coating, and/or prolonged release of the drug through semi permeable membrane [3].The recommended daily dose of Mesalamine may reach 4.8 g in acute attack and 2.4 g in maintenance of remission in divided doses. Therefore, multiple daily dosing up to 12 tablets or capsules per day are required because of the low dosage strength of most currently commercially available Mesalamine formulations. Reduced patient compliance and disease control are the results of these inconveniences of frequent daily dosing and the number of tablets or capsules required per day [4]. Additionally, many traditional delayed-release formulations that lack any means for prolonging Mesalamine release are characterized by the

Design and Evaluation of Novel High-load Mesalamine Multi-particulate Formulations for Colon-targeted Controlled Drug Delivery

“…Additionally, many traditional delayed-release formulations that lack any means for prolonging Mesalamine release are characterized by the undesirable immediate release of Mesalamine once they reach the colon. This leads to a relatively smaller amount of Mesalamine delivered to the distal part of the colon, the area most commonly to be inflamed [10,11].…”