Molecular docking and physicochemical characterisation of kaempferol-hydroxy propyl-β-cyclodextrin–Inclusion complex

Kaempferol is a poorly water-soluble flavonoid with limited biopharmaceutical performance, which restricts its formulation and delivery. In the present study, inclusion complexation of kaempferol with hydroxypropyl-β-cyclodextrin (HPβCD) was investigated using an integrated experimental and computational approach to evaluate its impact on physicochemical and permeability-related properties. The complex was characterised in the solid state by FT-IR, X-ray diffraction, and thermal analysis, and in solution by phase-solubility studies and ¹H NMR spectroscopy. Phase-solubility analysis indicated AL-type behaviour with a 1:1 stoichiometry and a stability constant in the order of 10³ M⁻¹. Complexation resulted in a 5.45-fold increase in aqueous solubility, a reduction in lipophilicity (log P), and improved apparent permeability compared with pure kaempferol. Molecular docking was employed as a qualitative tool to visualize host–guest interactions and support experimental findings. Overall, this study provides a systematic biopharmaceutical evaluation of kaempferol–HPβCD inclusion, highlighting how cyclodextrin complexation modulates solubility–lipophilicity–permeability relationships relevant to formulation development.Beyond structural characterisation, this study emphasises a physicochemical interpretation of how cyclodextrin–guest interactions modulate the solubility–permeability balance of kaempferol. By correlating experimental spectroscopic signatures with molecular docking-derived interaction patterns, the work provides mechanistic insight into how inclusion complexation alters drug hydrophilicity without compromising membrane transport. While inclusion complexes of kaempferol have been previously reported, the present work advances understanding by linking supramolecular host–guest interactions to functional transdermal performance parameters.