Enhancement of Mesalamine Solubility Using Spray-Dried Matrices of HPMCAS for Tablet Formulation

Abstract: Purpose: Mesalamine (5-aminosalicylic acid), a BCS Class IV drug used in ulcerative colitis and Crohn's disease, suffers from poor aqueous solubility and inconsistent colonic release. In order to improve solubility, dissolving rate, and site-specific distribution, this study developed spray-dried amorphous solid dispersions (ASDs) of mesalamine with HPMCAS and formulated them into compressible tablets. Methods: Spray drying was used to create five ASDs (F1–F5) with drug-to-polymer ratios ranging from 1:1 to 1:3. The drug concentration, flow characteristics, water solubility, and % yield of the formulations were assessed. DSC, PXRD, and SEM were used in solid-state characterisation. ASDs were crushed into tablets (T1–T5) and evaluated for in vitro dissolution at pH 1.2, 6.8, and 7.4 as well as post-compression characteristics. Results: Percentage yield ranged from 32–52%, with drug content of 90–93.3%. Solubility improved markedly over pure drug, peaking at the 1:2 ratio (0.8 mg/mL versus 5.8 mg/mL).DSC showed melting-point depression, and PXRD revealed reduced crystallinity, confirming amorphous conversion. SEM showed spherical, dimpled particle morphology. Tablets exhibited sustained drug release at pH 7.4, with cumulative release reaching 92–93% by 8 hours. Conclusion: Spray-dried mesalamine-HPMCAS ASDs successfully improved solubility and produced mechanically stable, compressible tablets with sustained, pH-dependent release, supporting their potential for improved colon-targeted therapy.