Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
University of Maryland School of Pharmacy, University of Maryland Computer Aided Drug Design Center, Baltimore, MD, USA.
Pharm Dev Technol. 2022 Apr;27(4):389-398. doi: 10.1080/10837450.2022.2064492. Epub 2022 Apr 25.
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.
本研究的重点是通过实验和计算研究来考察胆钙化醇（维生素 D3）与羟丙基-β-环糊精（HPBCD）络合的增溶作用。胆钙化醇（完全不溶于水）的相溶解度图呈现 A 型曲线，表明其与 HPBCD 浓度增加的线性回归存在偏差。差示扫描量热法（DSC）是通过胆钙化醇-HPBCD 复合热图谱中胆钙化醇的放热峰消失来确认络合形成的最佳工具，由于其进入 HPBCD 内部疏水性空腔而呈无定形态，同样通过傅里叶变换红外光谱（FTIR）和 X 射线衍射（XRD）得到验证。溶解度图的形态可与胆钙化醇-HPBCD 络合物在液相中的不稳定性相关联，需要喷雾干燥将其转化为固体分散状态（总是更稳定），这可以通过扫描电子显微镜（SEM）来证明。计算研究在分子水平上深入理解和阐明了胆钙化醇-HPBCD 络合物内部的相互作用。通过分子动力学（MD）模拟研究了络合物的热力学和几何结构。
