Werner Álvaro, Zuriaga Estefanía, Sanz Marina, Bergua Fernando, Giner Beatriz, Lafuente Carlos, Lomba Laura
Facultad de Ciencias de la Salud, Universidad San Jorge, Campus Universitario, Autov. A23 km 299, 50830 Villanueva de Gállego, Zaragoza, Spain.
Departamento de Química Física, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Zaragoza, Spain.
Pharmaceutics. 2025 Jul 29;17(8):979. doi: 10.3390/pharmaceutics17080979.
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. 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. 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. These findings highlight the potential of ibuprofen-menthol eutectic systems for safer and more effective pharmaceutical formulations.
近期的药物研究越来越关注低共熔体系，以改善活性药物成分（APIs）的制剂和递送。本研究介绍了三种基于布洛芬和薄荷醇不同摩尔比的治疗性低共熔体系（THEESs）的制备与表征。通过评估其物理化学性质来制备和分析THEESs，并对其流变性质进行评估以确定流动行为。在HaCaT和HepG2细胞系上进行细胞毒性试验以评估生物相容性。所有体系均形成单相、均匀、澄清且粘稠的液体。关键的物理化学性质，包括密度、折射率、表面张力、声速和等压热容，呈现出温度依赖性的反比趋势。粘度遵循Vogel-Fulcher-Tammann方程，流变学分析显示出非牛顿行为，这对药物加工很重要。值得注意的是，细胞毒性试验表明，在HaCaT细胞中，Ibu-M3和Ibu-M4的毒性低于纯化合物，而Ibu-M5毒性更大；在HepG2细胞中，只有Ibu-M3毒性较小，而Ibu-M4和Ibu-M5的细胞毒性比纯化合物更大。这些发现突出了布洛芬-薄荷醇低共熔体系在制备更安全、更有效的药物制剂方面的潜力。
