Cholecalciferol complexation with hydroxypropyl-β-cyclodextrin (HPBCD) and its molecular dynamics simulation.

The focus of the current study is to investigate cholecalciferol (vitamin D3) solubilization by hydroxypropyl-β-cyclodextrin (HPBCD) complexation through experimental and computational studies. Phase solubility diagram of vitamin D3 (completely insoluble in water) has an A profile revealing a deviation from a linear regression with HPBCD concentration increase. Differential scanning calorimetry (DSC) is the best tool to confirm complex formation by disappearance of cholecalciferol exothermic peak in cholecalciferol-HPBCD complex thermogram, due to its amorphous state by entering HPBCD inner hydrophobic cavity, similarly validated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). A solubility diagram profile can be associated with cholecalciferol-HPBCD complex instability in liquid phase requiring spray drying to bring it to a solid dispersion state (always more stable) illustrated by scanning electron microscopy (SEM). Computational studies led to a deeper understanding and clarification, at molecular level, of the interactions within cholecalciferol-HPBCD complex. Thermodynamics and geometry of the complex were investigated by molecular dynamics (MD) simulation.