Mesalamine premix-based delayed release formulation and its efficacy assessment using a 3D in-vitro gut model for inflammatory bowel disease.

Mesalamine is a widely used drug for inflammatory bowel disease (IBD) but suffers from limited solubility, permeability, and multiple formulation challenges. In this study, we tried to tune mesalamine's Biopharmaceutical Classification System (BCS) properties using premix technology to enhance its solubility and intestinal permeability, and to develop a delayed-release formulation. Mesalamine premix was prepared by the spray drying technique. Particle size analysis (PSA), solubility study, Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and in-vitro dissolution study were performed to characterize the premix. The premix showed reduced particle size, higher solubility, and lower crystallinity compared to pure mesalamine. Thermal analyses confirmed improved stability, while SEM revealed spherical morphology. Epithelial and endothelial permeability studies using Caco-2, HUVEC, and heterogeneous co-culture (Caco-2/HT-29/M1 macrophage) models assessed increased permeation potential. It shows its efficacy in a pro-inflammatory (M1) macrophage-induced intestinal inflammatory condition in a heterogeneous co-culture. An in-vitro dissolution study of the novel mesalamine delayed-release tablet showed no drug release at 0.1 N HCl (pH 1.2), and complete drug release at pH 6.8, while marketed tablets released the drug more slowly due to the enteric coating. Thus, the formulation approach showed potential as a delayed-release mesalamine oral formulation, which can be used for drug targeting to the colon without the need for a functional coating on the tablet.