Self-assembled precipitates from Gegen Qinlian decoction: Physicochemical characterization, in vivo and in vitro behaviors

Gegen Qinlian decoction (GQD), a traditional Chinese medicine used to treat infectious diarrhea, forms self-precipitates (GQD-P) during decoction. Although GQD-P and the supernatant (GQD-S) share an identical chemical composition, their physicochemical properties and in vivo behavior are not yet fully understood. This study aimed to investigate the physicochemical, in vitro , and in vivo properties of GQD-P, and to elucidate its unique role in the decoction's holistic efficacy. The morphology and pH-dependent dissolution of GQD-P were analyzed. Components in GQD, GQD-S, and GQD-P were quantified using HPLC, while pharmacokinetics of nine components were compared in rats administered GQD, GQD-S, or GQD-P using UPLC-MS/MS. GQD-P consisted of nanospheres whose dissolution was markedly enhanced under acidic, but not enzymatic, conditions. Baicalin and berberine were the main components of the primary precipitate framework. GQD-P components showed significantly prolonged MRT 0-t and T 1/2 , and delayed T max compared to GQD-S. The whole decoction exhibited a biphasic profile combining features of both phases, with GQD-P acting as a pH-triggered, sustained-release reservoir. Together with the rapid-release supernatant, it creates a biphasic system prolonging systemic exposure and collectively underpins the comprehensive efficacy of GQD.