This paper examines the effect of three protocols with several units and blender parameters on the mitigation of active pharmaceutical ingredient (API) agglomeration in solid formulations. The three protocols either preblend API with a portion of excipients in a high shear unit followed by dilution in a large blender or prepare the entire blend in a single blender followed by milling. In general, the three protocols yield blends with statistically similar API concentration variance and deagglorneration. The scale-up of the three protocols leads to more extensive API deagglomeration, which suggests that blender parameters still influence the degree of API deagglomeration, even when high shear units are present in the protocol. Lower blender fill levels and larger blenders lead to blends with fewer API agglomerates. Regarding the use of blender internals, results show that baffles have no substantial effect on API agglomeration. The inclusion of a moving internal (i.e., impeller) in a bin blender may not always lead to blends with fewer API agglomerates. The design and the positioning of the impeller play an important role as well.