Recently, the intensified vibratory milling (IVM) has emerged as a viable milling technology known for its nanosizing and high-throughput potential. The extent of the heat generation is ambiguously discussed within the literature. For this reason, the impact of formulation and process parameters for both particle size reduction and heat generation, needs further investigation to develop robust processes using the IVM technology. For this reason, the impact on particle size and heat generation of three different process parameters: – bead-suspension ratio; milling time; and acceleration – as well as one formulation parameter – API concentration – was investigated by a one-variable-at-a-time approach. Further the effect of additional fixtures on the heat generation was noted. The data obtained in this work showed that if the impact on heat generation was taken into account, the process parameters could be fine-tuned to optimize the nano-sizing potential while containing a continuous milling process. A longer milling time and production of highly concentrated formulations were proposed as gentle optimisation steps for the herein presented comminution process.