Complexation with β-cyclodextrin derivatives enhanced the bioavailability of quercetin through improving solubility and inhibiting recrystallization

HP-β-CD and M-β-CD exhibited stronger complexation capacity with quercetin (Que) than native β-CD. • The solid complexes of Que and β-CD derivatives were prepared by spray-drying. • The complexes significantly improved the dissolution and solubility, and suppressed the recrystallization of Que. • M-β-CD carrier exhibited better bioavailability enhancement effects on Que in rat than HP-β-CD. Quercetin (Que) is a common flavonol with diverse biological activities. Cyclodextrins (CD) were used to enhance the oral bioavailability of Que and the underlying mechanisms were explored anew. The complexation reactions between Que and β-CD, 2-hydroxypropyl-β-CD (HP-β-CD) and methyl-β-CD (M-β-CD) were characterized by phase-solubility analysis and UV-Vis spectroscopic titration. The results revealed that HP-β-CD and M-β-CD exhibited stronger complexation capacity than native β-CD. It was novelty discovered that the reversible complexation reaction effectively suppressed the recrystallization of supersaturated Que. The solid complexes of Que with HP-β-CD and M-β-CD were prepared by spray drying with a drug loading capacity of 4.67 ± 0.08%. The SEM, XRD and DSC analyses showed Que lost its crystal structure in the complexes, while FTIR revealed the interactions between Que and CDs. The complexes significantly improved the dissolution and solubility of Que. In addition to being dissolved, approximately 25% Que existed in nanoparticle form in simulated gastrointestinal fluids. M-β-CD effectively maintained the particles in nanoscale, whereas HP-β-CD failed. After oral administration, Que mainly exists in rat circulating blood as glucuronide metabolites. Pharmacokinetics revealed that, compared with free Que, M-β-CD and HP-β-CD complexes did not significantly increase the blood concentration of Que, but increased the AUC (0-t) of quercetin glucuronide metabolite (Que-Glu) by 7.52 times and 4.44 times, respectively. The primary novelty of this work is the finding that in addition to solubility improvement, the suppression of Que recrystallization through CD complexation is also an important mechanism for bioavailability enhancement. Download: Download high-res image (282KB) Download: Download full-size image