Solid dispersion of co-amorphous Phloretin-Trilobatin in Erythritol: A multifunctional premix for enhanced solubility and synergistic glycolipid regulation.

This study developed a novel ternary solid dispersion premix by dispersing phloretin-trilobatin co-amorphous mixture (1:2 M ratio) into erythritol via solvent evaporation to simultaneously enhance solubility and glycolipid-regulating bioactivity. The formulation markedly improved aqueous solubility, achieving >28-fold and > 15-fold increases for phloretin and trilobatin, respectively. Comprehensive characterization through powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy, combined with density functional theory and molecular dynamic simulations, verified a homogeneous amorphous structure stabilized by hydrogen bonding and hydrophobic interactions. In vitro evaluation demonstrated dual inhibition of pancreatic lipase and cholesterol esterase, synergistic suppression of α-glucosidase, and delayed starch digestion. Network pharmacology and molecular docking identified multi-target modulation of glycolipid metabolism via pathways including PI3K/AKT and MMP9. This food-grade, scalable approach offers a promising strategy for sugar-reduced functional ingredients, integrating solubility enhancement with metabolic benefits for managing hyperglycemia and hyperlipidemia in functional foods and beverages.