Molecular dynamics simulations to study the stability of isosorbide mononitrate solutions

The aggregation state of drug molecules in solution is a key factor affecting their efficacy and bioavailability, and propylene glycol has a wide range of applications as a solution stabilizing agent in drug injection formulations. In this work, molecular dynamics simulations were used to study the aggregation behavior of isosorbide mononitrate in three-volume fractions of aqueous solutions of propylene glycol. It was found that the aggregation probability of isosorbide mononitrate in solution decreased as the volume fraction of propylene glycol in solution increased. The interactions between drug molecules within the aggregates, the solvation state around the drug molecules, and the spatial distribution characteristics of solvent molecules around the drug molecules were investigated. In different volume fractions of propylene glycol aqueous solution, drug molecules are selective in forming hydrogen bonds with water and propylene glycol molecules; at the same time, there are certain differences in the type, number, and strength of hydrogen bonds in the hydrogen bonding network formed by solvent molecules around the drug molecules of isosorbide mononitrate. The interactions between drug molecules and solvent molecules and the hydrogen bonding network formed between solvent molecules together resulted in a lower self-diffusion coefficient of isosorbide mononitrate in a higher volume fraction of propylene glycol aqueous solution, a lower probability of formation of drug aggregates and a higher stability of the solution.