Molecular Dynamics Simulations of Polyoxyl-35 Castor Oil Microemulsions using Mesodyn
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 328-341
https://doi.org/10.22037/ijps.v22i1.46624
Abstract
Microemulsions (MEs) are transparent, thermodynamically stable mixtures of water and oil, stabilized by surfactants and cosurfactants, which facilitate their formation by reducing interfacial tension and enhancing solubility. Mesoscopic dynamics (Mesodyn) simulation has emerged as a powerful analytical approach for investigating the phase behavior and dynamic evolution of surfactants in solvents under real-world conditions. The objective of the current study was to utilize Mesodyn simulation tools to examine the phase behavior of MEs. In this study, coarse-grained models of Kolliphor EL (Polyoxyl-35 Castor Oil), Capmul MCM NF, and Transcutol P were developed. The phase morphologies, aggregation behavior, and miscibility of the components in the ME systems were studied. An attempt was made to correlate the Mesodyn predictions for pharmaceutical MEs with experimental measurements. Transcutol P (cosurfactant), Kolliphor EL (surfactant), and Capmul MCM (oil phase) were selected as the ME components based on solubility studies conducted in wet-laboratory experiments.
ME formulations were chosen based on the pseudo-ternary phase diagram. Oil and Smix (1:1) proportions varying from 1:9 to 9:1 were used to develop various MEs, which were then studied for their phase behavior. Various mesoscopic metrics, including density maps, order parameters, and thermodynamic parameters, were carefully analyzed. The simulation studies demonstrated the representation of the various ME components in Mesodyn using density maps. Homogeneity was observed in both the wet-laboratory and simulation studies for the 1:9 and 2:8 ME systems. By analyzing the P values of all systems, it was found that as the concentration of Smix and water increased, the rate of ME formation also increased. In this study, it was observed that as the oil-phase concentration increased, the hydrophobic effect became dominant, leading to a decrease in the Smix concentration. This led to immiscibility and phase separation, possibly due to higher interfacial tension. The 1:9 and 2:8 ME systems showed very low Gibbs free energy (ΔG) values, indicating the stability and spontaneity of ME formation. The laboratory results for ME formulations with 1:9 and 2:8 ratios were consistent with the simulation results, confirming that both formulations were homogeneous. Based on these findings, the ME system with a 1:9 (oil:Smix) composition was selected for further molecular dynamics (MD) simulations incorporating a drug. Despite the higher ΔG value, homogeneity was maintained upon drug incorporation. The order parameters remained almost unchanged compared to the blank system, indicating the suitability of the ME system for drug incorporation.
The outcomes of this work provide valuable insights for the future design and development of Kolliphor EL-based MEs loaded with BCS Class II drugs using the coarse-grained model.
- Materials studio
- Microemulsions
- Mesodyn simulations
- Coarse-grained model
- Phase morphology
- Molecular dynamic simulations
- Solubility Studies
How to Cite
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