Theoretical and experimental investigation of a nimesulide-alginate hybrid composite: Physicochemical characterization, cytotoxicity and release profile

Nimesulide (NIM) is a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), generally administered orally, with a distinctive pharmacological profile, that may still lead to some gastrointestinal adverse effects. Its combination with natural polysaccharides to develop modified-release delivery systems has become a technological strategy to reduce the adverse effects. In this work, we propose the development and characterization of a hybrid composite based on sodium alginate (NaCHO), nimesulide (C₁₃H₁₂N₂O₅S), and calcium chloride (CaCl₂). The synthesized hybrid composite – NaCHO-NIM-CaCl₂ – was developed by adapting methods of calcium-induced ionotropic gelation, sonication, and solvent evaporation. The obtained hybrid was characterized in terms of its physicochemical properties using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and Fourier-transform infrared (FT-IR) spectroscopy. Theoretical studies of the vibrational properties of NIM, NIM-CaCl₂ and the hybrid NaCHO-NIM-CaCl₂ were performed using density functional theory (DFT) for the first time. Electronic properties of the NIM crystal were elucidated, revealing that it is a semiconductor compound. For proof of concept, cell viability assay and in vitro release tests were performed to evaluate the potential biological application of NaCHO-NIM-CaCl₂.