Preparation, spectroscopy and molecular modelling studies of inclusion complex of vincamine with hydroxypropyl-β-cyclodextrin / 中草药

ABSTRACT

Objective The inclusion complex of vincamine (VIN) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared and characterized. Molecular simulation method was used to study the formation mechanism of inclusion complex. Methods The inclusion complex of VIN/HP-β-CD was prepared by saturated solution. The preparation technology of VIN/HP-β-CD inclusion complex was optimized by orthogonal design, and taking the drug-loading of the inclusion compound as the index. The stability constant of inclusion complex between VIN and HP-β-CD was studied by UV-Vis spectrometry titration, and the inclusion ratio was determined by Job plots method. The VIN/HP-β-CD inclusion complex was characterized by scanning electron microscope (SEM), X-ray powder diffractometry (XRD), infrared spectroscopy (IR), thermal analysis techniques (TG and DSC), and nuclear magnetic resonance (1H, 2D NMR). The water solubility of the VIN/HP-β-CD inclusion complex was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment. Molecular docking and molecular dynamics were used to study the forming mechanism of supramolecular system of VIN/HP-β-CD. Results Using saturated solution method, the optimum conditions of inclusion were 11 for molar ratio of VIN and HP-β-CD, 40 ℃ for inclusion temperature, 7 h for inclusion time and volume ratio of methanol to water (16) as solvent; Job curve and UV-vis spectroscopy showed that inclusion ratio of host-guest inclusion complexes was 11; After VIN formed inclusion complexes with HP-β-CD, its solubility increased from 0.04 mg/mL to 16.5 mg/mL, and the thermal decomposition temperature of VIN increased from 240.5 ℃ to 306.1 ℃. 1H-NMR and NOESY spectra indicated that the inclusion complex was formed by the a-ring of VIN entering from the large end of HP-β-CD. Quantum chemical calculation and molecular docking indicated that the optimal inclusion mode was consistent with the results of NMR studies. Molecular dynamics studies showed that VIN can penetrate into the hydrophobic cavity of HP-β-CD in water environment, and the interaction between host and guest was strengthened. The space size of host-guest matched better. Conclusion The solubility and thermal stability were significantly improved after the formation of inclusion complex with VIN and HP-β-CD. Hydrophobicity, hydrogen bonding, and van der Waals forces were the main driving forces for inclusion complex formation.