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The surface morphology of α-lactose monohydrate particles was modified by a new wet-smoothing process performed in a high-shear mixer using solvents. Successive steps of wetting and drying of lactose powders during rolling in the mixer's cylindrical bowl were performed. Smoothed particles were tested for size distribution, flow, and packing. The wet-smoothing process flattened the surface and rounded the edges of lactose particles. In comparison with original lactose, an improvement of powder packing and flow properties was evidenced. When the process was performed in the presence of a ternary agent such as magnesium stearate, the smoothing was improved. The evolution of rugosity during the smoothing process was assessed through a fractal descriptor of SEM picture. Atomic force microscopy and surface area measurements quantified the surface rugosity. A very significant reduction of the rugosity, more remarkable in the presence of magnesium stearate, was measured. This new process of powder wet-smoothing allows the preparation of lactose particles with different degrees of smoothed surface for the control of flow and packing properties and particle-particle interactions.