- 3:35 PM

On the Modeling of Milling In Pharmaceutical Industry

Nandkishor Nere1, Ryan McCann2, Kenneth Morris2, and Doraiswami Ramkrishna1. (1) School of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette, IN 47907-2100, (2) Department of Industrial and Physical Pharmacy, Purdue University, 480 Stadium Mall Drive, West Lafayette, IN 47907-2100

Milling of the active pharmaceutical ingredient is a significant unit operation practiced in the pharmaceutical and allied industry. Although it is simple in operation, the physics is complex and the milling behavior is difficult to predict from the first principles due to complicated interplay between various factors ranging from the breakage mechanisms and material properties in addition to operating conditions.

We present nonlinear breakage models to explain various observations reported in the literature based on the rational physics following the earlier work of Bilgili and Scarlett (2005). We show that the dynamics of the particle size distribution resulting due to certain nonlinear milling models also exhibits self-similarity that can very well be harnessed to extract models for both the breakage rates and daughter particle size distributions using the inverse problem approach developed by Sathyagal et al. (1994).

We show some interesting simulation results and validation of the adopted inverse problem approach for some model breakage rates and the daughter size distributions. It is also of interest to propose the methodology to relate the extracted breakage functions to the physics of the process and the operating parameters for two-stage hammer mill operated with screens in place that is a part of continuous tablet press.


1. Sathyagal, A. N.; Ramkrishna, D.; Narsimhan, G. Solutions of Inverse Problems in Population Balances II. Particle Break-Up. Comput. Chem. Eng. 19, (1995), 437.

2. Bilgili, E., Scarlett, B. Population balance modeling of non-linear effects in milling processes, Powder Technology 153, (2005), 59 71.