Efficient Discrete Element Method Simulation Strategy for Analyzing Large-Scale Agitated Powder Mixers Eva Siegmann 1 , Dalibor Jajcevic 1 , Charles Radeke 1 , Dieter Strube 2 , Karsten Friedrich 2 , and Johannes G. Khinast 1,3, * DOI: 10.1002/cite.201700004 Powder mixing is one of the most important pharmaceutical manufacturing operations. Computation methods are required to transform mixer design and scale-up from art to science. Due to an increase in the computational power and the development of graphics cards, the discrete element method is becoming a widely-used technique. For an industrial granular mixer, it is demonstrated that a smart simulation strategy together with a highly efficient code can reduce the simulation time. The good agreement between simulation and measurement data confirms that the simulation strategy can be applied to the product development. Keywords: Blending, Discrete element method, Granular flow, Mixing, Scaling Received: January 10, 2017; revised: March 17, 2017; accepted: May 05, 2017 1 Introduction Powder mixing (or blending) is an important pharmaceuti- cal unit operation for the homogenization of a product, e.g., the blending of active ingredients and excipients (fillers, dis- integrants, lubricants) or the distribution of liquids in a powder. Blending is strongly affected by the particle proper- ties (size distribution, density, cohesivity, shape) as well as moisture and electrostatics, leading to different methods of blending. During blending three main effects occur that compete at every time during the mixing process. These are (1) the mixing of particles by moving particles with respect to each other, (2) segregation due to a wide variety of mech- anisms, and (3) cohesive effects (van der Waals, electrostatic and capillary forces, and mechanical interlocking or sticki- ness due to melting). Three fundamental mechanisms are taking place during blending: – Diffuse mixing, i.e., the random motion of individual particles in the powder induced by energy transferred to the system and measured by the granular temperature. – Convective mixing, i.e., the transport of bulk material in a certain direction within the blender. Here particle transport is in the direction of the flow. Convection alone does not induce mixing. Only when particles of type A are convected in a region with type B particles, mixing occurs. – Shear mixing, i.e., due to the different velocities of differ- ent layers of the flow. Here particles in close proximity are removed from each other, leading to mixing. Segregation, i.e., the formation of spatial concentration differences of different particle types may be caused by a variety of different properties, including difference in size, density, shape, or surface characteristics. Typically, in blend- ing operations particle-size (or density) differences and cohesivity have the largest impact. Choosing the right type of mixer can be quite challenging, as demonstrated by ample literature in this field. The main types of mixers include tumbling blenders and agitated sys- tems, which are the focus of the current study. Understand- ing the effect of particle properties, such as shape, size, and mechanical parameters, on powder mixing efficiency is crit- ical for the design and optimization of these operations. In the last decade, the discrete element method (DEM) was increasingly used to study and analyze flows of particu- late systems with the main emphasis on granular flows, in which the interaction between the particles and the fluid phase can be neglected (i.e., only particle-particle interac- Chem. Ing. Tech. 2017, 89, No. 8, 995–1005 ª 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.cit-journal.com – 1 Eva Siegmann, Dr. Dalibor Jajcevic, Dr. Charles Radeke, Prof. Dr. Johannes G. Khinast Research Center Pharmaceutical Engineering GmbH, Inffeld- gasse 13, 8010 Graz, Austria. 2 Dr. Dieter Strube, Dr. Karsten Friedrich Gebru ¨der Lo ¨dige Maschinenbau GmbH, Elsener Straße 7 – 9, 33102 Paderborn, Germany. 3 Prof. Dr. Johannes G. Khinast khinast@tugraz.at Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13/III, 8010 Graz, Austria. Research Article 995 Chemie Ingenieur Technik