This study modeled the particle size distribution (PSD) of pharmaceutical extrudates after milling by developing a so-called time-discrete population balance model (PBM). The PBM, which models size reduction as a series of breakage events, was formulated so that the model parameters separate the effect of material properties and milling process conditions. Because of this novel aspect, the PBM should have excellent predictive capability with specific applications in technology transfer and scale-up. To investigate this application, copovidone extrudate produced by the hot-melt extrusion process was milled using a lab-scale continuous impact mill (Fitz Mill). The effect of impeller speed and classification screen size on PSD of the extrudate was investigated. The PBM with parameters obtained by fitting lab-scale PSD data was then applied to model the PSD of the extrudate following milling by a pilot-scale continuous impact mill (Hosokawa mill). The study found that the parameters determined at the lab-scale can be used to model PSDs at the pilot-scale and may be generally applied to similar classification-type impact mills. Since technology transfer and scale-up can be material and time consuming, this approach may offer significant benefits to the pharmaceutical industry for the development of milling processes. (C) 2018 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.