Additive Manufacturing of Regorafenib Tablets: Formulation Strategies and Characterization for Colorectal Cancer

Abstract

Significant efforts have been dedicated to developing controlled-release systems for the effective management of colorectal cancer. In this study, a once-daily, delayed-release regorafenib (REG) tablet was fabricated using 3D printing technology for the treatment of colorectal cancer. For this, a hydrogel containing 80 mg of the drug in a matrix of hyaluronic acid, carboxymethyl cellulose, Pluronic F127, and glycerol was prepared to incorporate into the shell cavity of tablet via a pressure-assisted microsyringe (PAM). The shell was printed from an optimized ink formulation of Soluplus®, Eudragit® RS-100, corn starch 1500, propylene glycol 4000, and talc through melt extrusion-based 3D printing. In vitro release assays showed a drug release rate of 91.1% in the phosphate buffer medium at 8 h and only 8.5% in the acidic medium. Drug release kinetics followed a first-order model. The results showed smooth and uniform layers based on scanning electron microscopy (SEM) and drug stability at 135 °C upon TGA. FTIR analysis confirmed the absence of undesired covalent interactions between the materials. Weight variation and assay results complied with USP standards. Mechanical strength testing revealed a Young’s modulus of 5.18 MPa for the tablets. Overall, these findings demonstrate that 3D printing technology enables the precise fabrication of delayed-release REG tablets, offering controlled-release kinetics and accurate dosing tailored for patients in intensive care units.