The objectives of this work were to implement on-line dynamic image analysis and to introduce a novel at-line flowability analyzer in pharmaceutical dry milling. We used a pilot-scale conical mill and flowability of a placebo granulate was monitored using a powder avalanching analyzer. Experiments were designed and evaluated by means of response surface methodology in conjunction with robustness testing. The process parameters impeller speed and screen size significantly affected the particle size distribution and flow rate of the milled granules. Feeder speed did not affect the particle size, but displayed a statistically significant influence on the flow responses. Robustness testing was able to capture the effect of noise factors on the responses and showed clear differences between different lots of the placebo granulate in addition to temperature-dependent changes in flow behavior. Thus, on-line dynamic image analysis and at-line flowability characterization, together as complementary process analytical tools, provided valuable information. The combined analysis was of particular interest for testing the process and noise factors so that future process development can profit from this advancement in dry millin
