基于量子计算探讨穿心莲内酯-氧化苦参碱共无定型物的稳定性
Stability of Andrographolide-oxymatrine Co-amorphous System Based on Quantum Computing
方晓萍 1郑皓雪 1卢山 1曹艳1
作者信息
- 1. 湖北中医药大学药学院,湖北武汉 430065
- 折叠
摘要
药物非晶化是提高难溶性药物溶解度和溶出度的有效方法,但较差的稳定性限制了该类药物的进一步开发.因此,该研究旨在从分子聚集的角度,探索穿心莲内酯-氧化苦参碱(AP-OMT)共无定型体系的稳定性机制.首先,通过溶剂挥发法制备AP-OMT共无定型物.其次,采用分子动力学模拟计算组分间的相容性.最后,采用Gaussian 16软件计算AP-OMT共无定型物中由多个氢键模式组成的分子聚集体的键能与键距,并通过稳定性考察对其进行了验证.量子计算研究结果显示,二聚体4的相互作用能为负值(最小)且氢键键长最短,表明二聚体4是共无定型体系中最稳定的聚集体.稳定性研究表明,AP-OMT共无定型物在12个月内物理稳定性良好.该研究揭示了 AP-OMT二元共无定型体系的稳定性机制,为该类药物的稳定性研究提供了理论指导.
Abstract
Amorphization is an effective method to improve the solubility and dissolution of poorly water-soluble drugs.However,the poor stability limits the further development of amorphous drugs.Therefore,this study aimed to explore the stability mechanism of the andrographolide-oxymatrine(AP-OMT)co-amorphous system from the perspective of molecular aggregation.At first,the AP-OMT co-amorphous system were prepared by solvent volatilization method.Then,molecular dynamics simulations were used to calculate and evaluate the compatibility within the components.Finally,Gaussian 16 software was used to calculate the bond energies and bond distances of molecular aggregates consisting of multiple hydrogen bonding modes in the co-amorphous AP-OMT,which were verified by stability investigation.Quantum computing studies revealed that dimer 4 had the largest interaction energy(with negative value)and the shortest hydrogen bond length,indicating that dimer 4 was the most stable aggregate in the co-amorphous system.Stability studies showed that the AP-OMT co-amorphous system was physically stable over a period of 12 months.This study revealed the stability mechanism of the binary co-amorphous system of AP-OMT and provided theoretical guidance for the stability study of this class of drugs.
关键词
穿心莲内酯/氧化苦参碱/共无定型/稳定性/量子计算/二聚体Key words
andrographolide/oxymatrine/co-amorphous/stability/quantum computing/dimer引用本文复制引用
出版年
2024
NETL
NSTL
万方数据