Integrated in silico formulation design of selfemulsifying drug delivery systems  

作　　者：Haoshi Gao Haoyue Jia Jie Dong Xinggang Yang Haifeng Li Defang Ouyang 

机构地区：[1]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences(ICMS),University of Macao,Macao 999078,China [2]Institute of Applied Physics and Materials Engineering,University of Macao,Macao 999078,China [3]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第11期3585-3594,共10页药学学报（英文版）

基　　金：financially supported by the Science and Technology Development Fund(FDCT)of Macao(0029/2018/A1,China);the University of Macao Research Grants(MYRG2019-00041-ICMS,China);performed in part at the High-Performance Computing Cluster(HPCC)which is supported by Information and Communication Technology Office(ICTO)of the University of Macao,China。

摘　　要：The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

关 键 词：Self-emulsifying drug delivery system Random forest Central composite design Molecular dynamic simulation MELOXICAM 

分 类 号：R943[医药卫生—药剂学]