Comparative Pharmacokinetics and Safety of a Micellar Chrysin–Quercetin–Rutin Formulation: A Randomized Crossover Trial

Abstract

Chrysin is a dietary flavonoid with antioxidant and anti-inflammatory activity, but its clinical potential is limited by poor oral bioavailability. This randomized double-blind three period crossover trial evaluated the pharmacokinetics of a novel micellar chrysin formulation co-encapsulated with quercetin and rutin (LMC) compared with a non-micellar chrysin formulation (NMC) and unformulated chrysin (UFC). Secondary objectives included in vitro permeability (Caco-2) and a 30-day safety assessment of daily LMC supplementation. Sixteen healthy adults received a single oral dose of each formulation in randomized order separated by a 7-day washout. Plasma chrysin was quantified over 24 h to determine pharmacokinetic parameters. In vitro Caco-2 assays evaluated permeability, and clinical biochemistry of 15 participants were assessed weekly during 30 days of daily LMC use. LMC achieved >2-fold higher systemic exposure than unformulated chrysin (AUC0–24 = 914.8 ± 697.5 ng·h/mL; Cmax = 87.3 ± 59.4 ng/mL; both p < 0.05) and >2.6-fold higher than NMC, supported by >10-fold higher in vitro permeability. Daily LMC supplementation was well tolerated, with only mild, reversible adverse events and no clinically relevant safety changes, despite higher systemic exposure. Small, but significant, reductions in fasting glucose were observed in both sexes. The novel micellar chrysin–quercetin–rutin formulation substantially improved bioavailability and was well tolerated during 30 days of daily use, supporting its potential as an advanced delivery strategy for flavonoids with poor oral absorption and identifying glucose regulation as a physiological effect of interest.