Objective To investigate the compositional distribution, in vitro release, and pharmacokinetic behavior of different phases in the Huangqin (Scutellariae Radix, SR)-Zhigancao (Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, GRRPM) decoction, and to elucidate the physical structural basis for the delayed and enhanced efficacy mediated by herb compatibility. Methods The decoction was separated into nanoparticulate, true solution, and precipitate phases by centrifugation combined with dialysis. The particle size and morphology of these phases were characterized. The contents of major active components baicalin, wogonoside, liquiritin apioside, glycyrrhizic acid, and others were determined by HPLC, and their in vitro release profiles were evaluated. The plasma concentration of baicalin in rats after oral administration of different phases was measured using LC-MS/MS, and pharmacokinetic parameters were calculated. Results Significant differences in particle size and morphology were observed among the phases. The mass fractions of liquiritin apioside, baicalin, wogonoside, and glycyrrhizic acid in each phase decreased in the order: nanoparticulate phase > true solution phase > precipitate phase. All four components showed the highest release from the nanoparticulate phase, followed by the true solution phase, and the lowest release from the precipitate phase. After oral administration of the whole extract and the different phases, the C_max and AUC_0-t of baicalin ranked as follows: nanoparticulate phase > whole extract > true solution phase > precipitate phase. Conclusion The formation of a complex multiphase system in the SR-GRRPM decoction significantly affects the spatial distribution, in vitro release, and pharmacokinetic behavior of the active constituents. This may represent the physical structural basis underlying the delayed and enhanced efficacy resulting from the combination of the two herbs.

compatibility  /  Scutellariae Radix  /  Glycyrrhizae Radix et Rhizoma Praeparata cum Melle  /  phase difference  /  component distribution  /  in vitro release  /  pharmacokinetics