Preparation and characterization of inclusion complexes formed between baicalein and cyclodextrins

This study investigates the solubility of baicalein (Ba) with the addition of modified cyclodextrins using phase solubility method. The solubility of Ba in the presence of natural (α-, β-, and γ-) cyclodextrins and its derivatives, namely, hydroxypropyl-β-cyclodextrin (HP-β-CD) and (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), was higher than that of free Ba. In particular, the stability constant of inclusion complex with DM-β-CD was 13672.67 l mol−1, which was the highest among the examined cyclodextrins. The inclusion complexes of Ba and DM-β-CD were prepared via freeze-drying method, which were both characterized in the solution and solid state by UV–vis spectroscopy, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR), scanning electron microscopy (SEM), and X-ray powder diffractometry (XRPD). The UV–vis, DSC, 1H NMR, SEM, and XRPD results proved the formation of inclusion complex between Ba and DM-β-CD. Furthermore, the dissolution rate and thermal stability of the inclusion complex were significantly enhanced compared with the pure drug. Therefore, using DM-β-CD can effectively improve the solubility and thermal stability of free Ba, which is a promising approach to promote its clinical application.

► 1:1 complex of baicalein (Ba) with (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) was prepared and characterized.
► By complexation with CDs, the water solubility of Ba was improved.
► The highest value of the stability constant was for Ba/DM-β-CD inclusion complex.
► By complexation with DM-β-CD, the stability and dissolution rate of Ba were enhanced.