Development and Optimization of a Colon-Targeted Delayed-Release Mesalamine Tablet Using Dual Methacrylate Polymer Coating: A Generic Development Strategy for High-Variability Drug Products

Mesalamine (5-aminosalicylic acid) is the first-line therapy for the treatment of ulcerative colitis and mild-to-moderate Crohn’s disease. However, successful therapy depends on precise delivery of the drug to the colon while preventing premature release in the upper gastrointestinal tract. Development of generic delayed-release (DR) Mesalamine formulations remains challenging due to the drug’s high intrinsic pharmacokinetic variability, local site-specific action, and the critical influence of enteric coating characteristics on drug release behavior. The present study aimed to develop and optimize a colon-targeted delayed-release Mesalamine tablet through systematic core formulation and coating optimization. Core tablets containing 800 mg Mesalamine were prepared by wet granulation and evaluated against coat-removed reference listed drug (RLD) tablets to establish similarity in core release characteristics. Eight core formulations (F01–F08) were investigated, and formulation F08 demonstrated the closest dissolution similarity to the coat-removed RLD (f2 = 80.4). Subsequently, enteric coating formulations comprising Eudragit® S100 and Eudragit® L100 were evaluated at coating build-ups ranging from 5.0% to 8.0% w/w. The optimized formulation (F013) containing a 6.5% coating build-up exhibited dissolution behavior comparable to the RLD, achieving an f2 value of 75.1. The optimized formulation successfully prevented drug release in acid and pH 6.0 buffer stages while providing rapid and complete release in pH 7.2 phosphate buffer. Accelerated stability studies conducted at 40°C/75% RH for three months demonstrated acceptable assay, dissolution performance, moisture content, and impurity profiles without significant changes. The study demonstrates that a scientifically designed dual-polymer coating system combined with optimized core formulation can successfully overcome the formulation challenges associated with delayed-release Mesalamine products. The proposed development strategy provides a practical framework for future generic development of high-variability colon-targeted drug products.