Proposal of stability categories for nano-dispersions obtained from pharmaceutical self-emulsifying formulations.

Lipid-based formulations that disperse in water as nano-droplets are of considerable pharmaceutical interest. However, there is a recent debate on which systems form stable swollen micelles rather than other thermodynamically unstable nano-emulsions. This study introduces stability categories for nano-dispersions by considering theoretical arguments of particle size and polydispersity. In a second step, 20 pharmaceutical nano-emulsifying formulations were investigated with respect to the physical stability of the aqueous dispersions. Thermo-reversibility was studied using dynamic laser light scattering, ultrasonic resonator technology and near-infrared (NIR) analytical centrifugation. As a result, the majority of the dispersions were indeed nano-emulsions that exhibited only kinetic stability. Dispersions that were stable following the heat stress test were then further evaluated with respect to an alternative compounding other than dilution from a preconcentrate. Seven dispersions were hereafter deemed to be stable in the thermodynamic sense because they exhibited the same light scattering results independent of their compounding method. In conclusion, the proposed stability categories were shown to successfully assign dispersions. This has a general importance and can, for example, be applied when nano-dispersions are used as pre-clinical formulations.