Inclusion Complexes of Cholecalciferol (vitamin D3) with Hydroxypropyl-β-Cyclodextrin

Cholecalciferol (vitamin D3) deficiency is a significant threat to human health. The disadvantages of current cholecalciferol-based drugs are due to the low bioavailability of the vitamin D3 caused by its low solubility, gastrointestinal absorption, and first-pass oxidative metabolism. The nanotechnology progress provide a promising paradigm simultaneously addressing challenges such as poor solubility, low bioavailability, and instability. Innovative encapsulation platforms are designed to protect compounds, improve their delivery, and provide their stable on-target efficiency. In the present work, we report a synthesis of solid dispersions of vitamin D3 with hydroxypropyl-β-cyclodextrin (HP-β-CD) forming intermolecular complexes in aqueous solutions. It is shown that the solubility of vitamin D3 can be significantly (more than 300-fold) increased when it is used as a complex with HP-β-CD. It is shown using a solubility diagram that the aqueous solution is a mixture of complexes with stoichiometry 1:1 and 1:2. Stability constants of these complexes are calculated. It is determined by dynamic NMR spectroscopy that vitamin D3 molecules are incorporated into cyclodextrin cavities. The structure of inclusion complexes with stoichiometry 1:1 and 1:2 is characterized using molecular dynamics simulations.