Enhanced solubility, stability, and bioavailability of astilbin via inclusion complexes formation with methyl-β-cyclodextrin

Methyl-β-cyclodextrin (M-β-CD) exhibited the strongest complexation ability with astilbin (Ast) among three β-CD derivatives, i.e., M-β-CD, 2-hydroxyethyl-β-CD, and sulfobutylether-β-CD. The complexation reaction was investigated by UV spectroscopy, phase solubility, and NMR analysis. In simulated intestinal fluid (SIF), M-β-CD resulted in significant changes of Ast UV spectra through hindering the dissociation of 7-OH by complexation. Their formation constants ( K a) in water, simulated gastric fluid (SGF), and SIF were determined by the UV titration method with values of 6148.2 ± 558.9, 6596.3 ± 346.1, and 4602.2 ± 158.4 M⁻¹ , respectively. The Job’s plot showed that M-β-CD and Ast formed 1:1 inclusion complexes. Thermodynamic results revealed that the complexation was unfavourable at high temperature with negative ΔH and ΔS. The solubility of Ast linearly rose from 0.35 ± 0.03–3.57 ± 0.10 mM with the increase of M-β-CD concentration from 0 to 5.0 mM. The NMR analysis implied that the A ring of Ast was preferentially embedded in M-β-CD cavity. The Ast/M-β-CD complexes were prepared by co-grinding method and further characterized by SEM, XRD, DSC and FT-IR. These analysis revealed that Ast lost its crystal structure after complexation, and the secondary interactions between Ast and the M-β-CD were found. The complexes significantly improved the dissolution and solubility of Ast (>43 mg/mL). Furthermore, M-β-CD suppressed the crystallization of Ast, thereby maintaining its supersaturated status. Besides, the stability of Ast in SIF and SGF was also improved. Pharmacokinetic studies showed that Ast/M-β-CD complexes significantly enhanced the oral bioavailability of Ast by 11.89 times with C max of 642.28 ng/mL in rat plasma.