Investigating the Formation and Molecular Solubilization Mechanism of Emodin Solid Dispersions by Molecular Dynamics Simulation

Abstract

The preparation of solid dispersions (SDs) of emodin (EMO) represents an effective strategy for enhancing its limited water solubility. However, there is a lack of effective strategies for carrier screening. The molecular mechanism underlying EMO-SDs has yet to be fully elucidated. In this study, we employed a molecular simulation to identify the optimal solubilizing carriers for EMO-SDs, which were subsequently validated through solubilization experiments. Gelucire 50/13 (GEL) was identified as the most effective solubilizing carrier. The formulation of the EMO-SDs was established through solubility testing, utilizing a drug-to-carrier loading ratio of 1:9. The characterization of the interactions between the drug and the carrier was conducted using DSC, FTIR, and NMR spectroscopy. The DSC results indicated that EMO molecules were dispersed within the carrier in an amorphous state, while FTIR and NMR analyses revealed the formation of hydrogen bonds between the drug and carrier molecules. The molecular mechanisms of EMO-SDs were further elucidated through an MD simulation. Findings from the formation mechanism studies demonstrated that the majority of EMO molecules were embedded within the interstices of a loosely aggregated micelle-like structure formed by the carrier molecules. The solubility enhancement mechanism indicated that the carrier molecules surrounded the EMO molecules during the solubilization process, thereby facilitating the interaction of EMO with water. The stability mechanism accounts for the fact that recrystallization of the drug may occur.

Keywords

• emodin
• solid dispersions
• molecular dynamics simulation
• formation mechanism
• solubilization mechanism