Stability of Andrographolide-oxymatrine Co-amorphous System Based on Quantum Computing
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.
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