Granular flows have been the Achilles heel of industrial development. In the past years, the glidant (flow-aids) addition, mostly amorphous silica nanoparticles (S-NP), has become a step in formulation to ensure the process feasibility. Human and environmental exposure to S-NP has not been thoroughly evaluated, raising concerns about their toxicity. The action mechanism of glidants on flowability has been mainly attributed to a reduction of van der Waals forces, acting as spacers among the particles. Notwithstanding, other action mechanisms could alter the flow, such as friction or surface energy modifications. This work aims to evaluate these action mechanisms through a D-optimal experimental design. Results indicate that the friction plays no role in complex granular flows when interparticle forces act on the rheology. Flow enhancement is surface-related, mainly related to microscopic grain-level properties. The size of the S-NP depends on the grain-to-glidant interactions, which define the surface coverage and flowability. Finally, a formulation strategy focusing on the surface coverage is presented to mitigate the risk.