Mechanism of Precipitation Formation and Solubilization Strategy Research in Baihe Gujin Oral Liquid

To elucidate sediment formation in Baihe Gujin oral liquid (BGO) and optimize its stabilization, this study used ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), physicochemical analysis, surfactant screening, zeta potential measurement, and high-performance liquid chromatography (HPLC) fingerprinting. The precipitate mainly contained hydrophobic constituents (organic acids, flavonoids, alkaloids) with low flexibility and high logP. Surfactant screening showed that Tween 80 most effectively stabilized the system, reducing turbidity from 202.5 ± 1.0 to 118.0 ± 0.2 NTU, particle size from 5334.7 ± 2178.5 to 587.5 ± 36.3 nm, and PDI from 1.000 ± 0.000 to 0.495 ± 0.074, while increasing absolute zeta potential from -10.8 ± 1.3 to -28.6 ± 1.7 mV. Concentration optimization identified 0.6% Tween 80 as optimal, achieving turbidity of 110.6 ± 0.5 NTU, particle size of 321.9 ± 103.0 nm, PDI of 0.299 ± 0.034, and zeta potential of -32.4 ± 1.8 mV. Higher concentrations (0.7%-0.8%) reduced performance. HPLC fingerprints showed no major chemical changes after Tween 80 addition (similarity > 0.9). Thus, 0.6% Tween 80 improves BGO stability via micellar solubilization and electrostatic repulsion without altering the material basis.