Stability evaluation and characterization of oil-in-water emulsion using Methyl-α-Z)-Glucopyranoside and span surfactant series with molecular dynamic simulation

Oil-in-water (O/W) emulsions are widely utilized in pharmaceutical, food, and cosmetic applications for the delivery of lipophilic compounds, yet their inherent thermodynamic instability requires the use of suitable surfactants to reduce interfacial tension and enhance structural integrity. This study investigates the formulation and stability behaviour of virgin coconut oil (VCO)-in-water emulsions prepared with methyl-a-Dglucopyranoside (MEG), Span 20, and Span 80 as non-ionic emulsifiers. Both singlesurfactant and mixed-surfactant systems were developed and tested across five temperatures (30 °C, 35 °C, 40 °C, 45 °C, and 60 °C) to assess their robustness under thermal stress. Stability evaluations were conducted using creaming index measurement, rheological profiling, droplet size distribution via optical microscopy, FTIR spectroscopy, and molecular dynamics (MD) simulations. Results indicated clear performance differences between surfactant systems. The formulation containing a 30:40:15:15 ratio of oil: water: Span 20: MEG (Sample MS20-C) demonstrated the strongest stability profile. MS20-C recorded 0% phase separation at 30 °C after 30 days, in contrast to >20% separation observed in Span 80-based emulsions. Rheological analysis revealed pronounced shear-thinning behavior, with MS20-C exhibiting the highest viscosity among all samples, suggesting stronger droplet interactions and the formation of a more structured internal network. Microscopy confirmed uniformly distributed droplets without significant coalescence or large aggregates, reinforcing its macroscopic stability. FTIR results showed enhanced O-H and C-0 stretching vibrations in MEG-containing systems, indicative of stronger hydrogen bonding and a wellorganized interfacial film. MD simulations further supported these findings at the molecular level: MS20-C reached equilibrium at approximately 20 ns and maintained a stable radius of gyration (3.0-3.2 x 106 nm), together with a moderate eccentricity value (e = 0.308), reflecting compact molecular packing and near-spherical droplet geometry. These characteristics collectively suggest reduced shape deformation and lower susceptibility to instability mechanisms such as coalescence. Overall, the integrated experimental and simulation results confirm a strong synergistic stabilization effect between Span 20 and MEG, producing emulsions with superior thermal and structural stability. The findings highlight the potential of this mixed-surfactant system for highperformance, sustainable, and temperature-resilient formulations relevant to food, cosmetic, and pharmaceutical applications.