Molecular Dynamics Simulation of Drug Solubilization Behavior in Surfactant and Cosolvent Injections

Surfactants and cosolvents are often combined to solubilize insoluble drugs in commercially available intravenous formulations to achieve better solubilization. In this study, six marketed parenteral formulations with surfactants and cosolvents were investigated on the aggregation processes of micelles, the structural characterization of micelles, and the properties of solvent using molecular dynamics simulations. The addition of cosolvents resulted in better hydration of the core and palisade regions of micelles and an increase in both radius of gyration (R_g) and the solvent accessible surface area (SASA), causing a rise in critical micelle concentration (CMC), which hindered the phase separation of micelles. At the same time, the presence of cosolvents disrupted the hydrogen bonding structure of water in solution, increasing the solubility of insoluble medicines. Therefore, the solubilization mechanism of the cosolvent and surfactant mixtures was successfully analyzed by molecular dynamics simulation, which will benefit future formulation development for drug delivery.