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-beta-cyclodextrin (HPBCD) complexation through experimental and computational studies. Phase solubility diagram of vitamin D3 (completely insoluble in water) has an A(p) 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(p) 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.

Automated summary

The current study aims to investigate the solubilization of cholecalciferol (vitamin D3) by hydroxypropyl-beta-cyclodextrin (HPBCD) complexation. Experimental and computational studies were conducted to understand the thermodynamic and molecular aspects of the cholecalciferol-HPBCD complex. The results confirmed the formation of the complex and provided insights into the interactions at the molecular level.