The role of Surface Tension Measurement in Lipid Nanoparticle Formulation

Solid lipid nanoparticles (SLN) are attractive nanocarriers for drug delivery and diagnostic applications. Their formulation requires surfactants that reduce interfacial tension and form a protective layer around the nanoparticles, controlling particle size distribution and ensuring dispersion stability. However, both insufficient and excess surfactant concentrations can promote aggregation, through incomplete interfacial coverage and micellisation-induced surfactant depletion, respectively. This work highlights surface tension measurement as a screening test for selecting the optimal surfactant concentration during SLN formulation.

SLN were prepared by hot melt emulsification method with 1% Compritol ATO888 as the lipidic matrix. Poloxamer 407 and soy lecithin were used as surfactants, either individually or in 1:1 ratio. The surfactant concentrations were ranged from 0.02 to 2% (m/v). Particle size (PS) and polydispersity index (PDI) were assessed by Dynamic Light Scattering (DLS) at 25°C.

The surface tensions of SLN dispersions and those of aqueous surfactant solutions were investigated with Du Noüy ring method at 25°C and 45 °C.  Critical micelle concentrations (CMC) were determined graphically.

Surface tension measurements indicated distinct thermal behavior among the surfactants, with lecithin exhibiting greater temperature sensitivity at 45°C, decreasing by 0.55 mN/m per °C. The CMC determination for the individual surfactant solutions and their 1:1 mixture revealed a mild antagonism, which may limit surface adsorption at the particle interface. Consistent with this, SLNs prepared with a 0.02% surfactant mixture exhibited a particle size of 246±1.5 nm and higher surface tension than the corresponding surfactant mixture solutions. Furthermore, the evolution of SLN PS and PDI as a function of surfactant mixture concentration remained stable at concentrations between 0.15–0.5%, and increased significantly above 0.5%, suggesting the potential presence of micelles.

These findings provide insight into the surface phenomena affecting SLN stability and offer a rational basis for selecting the optimal surfactant concentration.