In this work Response Surface Methodology and Central Composite Rotatable Design were applied to find high-energy mixing process parameters enabling flow properties of highly cohesive Disulfiram powder to be improved. Experiments were conducted in a planetary ball mill. The response functions were created for an angle of repose and compressibility index as measures of powder flowability. To accomplish an optimisation procedure of mixing process parameters according to a desirability function approach, the results obtained earlier for potato starch, as another cohesive coarse powder, were also employed. Coupling these results with those achieved in a previous work, it was possible to develop some guidelines of practical importance allowing mixing conditions to be predicted towards flow improvement of fine and coarse powders.