In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

Xia Cao*, Wen-Wen Deng*, Min Fu*, Liang Wang, Shan-Shan Tong, Ya-Wei Wei, Ying Xu, Wei-Yan Su, Xi-Ming Xu, Jiang-Nan Yu
Department of Pharmaceutics, School of Pharmacy, and Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People’s Republic of China
*These authors contributed equally to this work

Background: The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles.
Methods: Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na₂CO₃ solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner-Nelson method was used to calculate the in vivo absorption fraction.
Results: The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50–100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m²/g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na₂CO₃ solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro–in vivo correlation revealed that HMSNs in 0.08 M Na₂CO₃ solution had a correlation coefficient R² value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively.
Conclusion: The findings of in vitro–in vivo correlation indicate that HMSNs together with Na₂CO₃ solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of water-soluble drugs.

Keywords: hollow-type mesoporous silica nanoparticle, silybin meglumine, in vitro dissolution, in vivo absorption, in vitro–in vivo correlation