Exploring Ibuprofen–Menthol Eutectic Systems: Physicochemical Properties and Cytotoxicity for Pharmaceutical Applications

Backgroun/Objectives: Recent pharmaceutical research has increasingly focused on eutectic systems to improve the formulation and delivery of active pharmaceutical ingredients (APIs). This study presents the preparation and characterization of three therapeutic eutectic systems (THEESs) based on ibuprofen and menthol at various molar ratios. Methods: The THEESs were prepared and analyzed by assessing their physicochemical properties and rheological properties were evaluated to determine flow behavior. Cytotoxicity assays were conducted on HaCaT and HepG2 cell lines to assess biocompatibility. Results: All systems formed monophasic, homogeneous, clear and viscous liquids. Key physicochemical properties, including density, refractive index, surface tension, speed of sound and isobaric heat capacity, showed a temperature-dependent, inverse proportional trend. Viscosity followed the Vogel-Fulcher-Tammann equation, and rheological analysis revealed non-Newtonian behavior, which is important for pharmaceutical processing. Notably, cytotoxicity assays revealed that Ibu-M3 and Ibu-M4 showed lower toxicity than pure compounds in HaCaT cells, while Ibu-M5 was more toxic; in HepG2 cells, only Ibu-M3 was less toxic, whereas Ibu-M4 and Ibu-M5 were more cytotoxic than the pure compounds. Conclusions: These findings highlight the potential of ibuprofen-menthol eutectic systems for safer and more effective pharmaceutical formulations.