Oral bioavailability enhancement of chrysin using a spray-dried solid dispersion formulation with sodium dodecyl sulfate and polyvinylpyrrolidone

초록

Purpose Chrysin has many pharmacological activities but suffers from low bioavailability (BA) due to its poor solubility and intestinal first-pass effect. This study aimed to develop a chrysin formulation that enhances its BA by inhibiting intestinal metabolism and increasing solubility. Methods A solid dispersion of chrysin (chrysin-SD) was prepared using the spray-drying method and characterized for solubility, metabolic inhibition, and pharmacokinetic properties of chrysin-SD in rats. Results Sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP) were selected as solubility-enhancing surfactants as well as inhibitors of chrysin glucuronidation and hydrophilic carriers, respectively. The optimized formulation had a chrysin: SDS: PVP ratio of 1:5:3 (w/w/w). Chrysin-SD increased chrysin solubility by 848-fold and the dissolution rate to 72.3% of the initial amount, compared to 3.11% for pure chrysin. This improvement was attributed to SDS, PVP, and the amorphous nature of chrysin-SD. Additionally, chrysin-SD increased absorptive permeability in the duodenum, jejunum, and ileum by 2.99- to 7.33-fold in rat models, without affecting secretory permeability. Chrysin-SD also suppressed the formation of chrysin glucuronide (chrysin-G), suggesting enhanced intestinal absorption through increased intestinal permeability and decreased intestinal glucuronidation. These findings were confirmed by a 19.7-fold increase in chrysin’s area under the curve (AUC) and a 93% reduction in the chrysin-G metabolic ratio compared to the pure chrysin group. Conclusion The chrysin-SD formulation with a chrysin: SDS: PVP ratio of 1:5:3 (w/w/w) significantly enhanced chrysin’s BA. This strategy, which improves solubility, dissolution, and intestinal absorption while reducing metabolism, offers a promising approach for enhancing the oral BA of herbal medicines like chrysin.

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