Particle size enlargement via agglomeration is widely used in industries spanning pharmaceuticals, food, and chemicals. However, during manufacture of an active pharmaceutical ingredient (API), agglomeration can be undesired, as the nature and material properties of the agglomerates can pose a risk to the API physical property control and negatively impact the performance during drug product processing. This paper presents a holistic framework to assess the propensity of particle agglomeration by systematically studying the rheological behavior of particles as a function of liquid saturation. The effect of intrinsic materials properties was investigated by a mixer torque rheometer, and particle size and surface properties were shown to be important factors for agglomeration. The extent of agglomeration and the size and strength of agglomerates rapidly increased when the API particles were subjected to mixing with a solvent content inside the "sticky zone". These results indicate the importance to fundamentally understand the relationship of particle materials properties and agglomeration behavior in the design of pharmaceutical unit operations.