DEM simulation of the mixing behavior in a spheronization process

Abstract Spherical pellets for pharmaceutical applications are widely produced by an extrusion-spheronization process. To achieve an equal, spherical pellet shape with a spheronization process, it is crucial that all pellets are exposed to similar stress conditions. However, in a spheronizer the pellets close to the friction plate are subjected to much higher stresses than pellets at the top of the torus, resulting in a strongly inhomogeneous stress distribution within the particle bed. Therefore, the product quality depends in particular on the mixing process in the spheronizer. In this study, the mixing behavior in a spheronization process is analyzed using DEM simulations. The real geometry and realistic process parameters of a lab scale spheronizer were investigated. To determine the mechanical properties of the wet pellets for the contact model, various single particle experiments were conducted with MCC-based pellets produced by extrusion-spheronization. The spatial mixing was characterized in different ways. Besides the determination of the degree of mixing based on statistical analysis, the Fokker-Planck equation was utilized. In this way the spatial distribution of the degree of mixing over the time was obtained. By using the poloidal distribution of the transport and dispersion coefficients of the Fokker-Planck equation the course of the degree of mixing in the different zones of the spheronizer was clarified.

[1]  François Bertrand,et al.  Discrete element investigation of flow patterns and segregation in a spheronizer , 2013, Comput. Chem. Eng..

[2]  Stefan Heinrich,et al.  Energy absorption during compression and impact of dry elastic-plastic spherical granules , 2010 .

[3]  Stefan Heinrich,et al.  CFD–DEM study and direct measurement of the granular flow in a rotor granulator , 2013 .

[4]  A. D. Fokker Die mittlere Energie rotierender elektrischer Dipole im Strahlungsfeld , 1914 .

[5]  S. Antonyuk,et al.  Partikelkinematik in der Sphäronisation pharmazeutischer Pellets , 2017 .

[6]  Stefan Heinrich,et al.  Experimental study of oblique impact of particles on wet surfaces , 2016 .

[7]  B. N. Asmar,et al.  A generalised mixing index in distinct element method simulation of vibrated particulate beds , 2002 .

[8]  R. L. Braun,et al.  Stress calculations for assemblies of inelastic speres in uniform shear , 1986 .

[9]  P. Lacey The mixing of solid particles , 1997 .

[10]  Harald Kruggel-Emden,et al.  Review and extension of normal force models for the Discrete Element Method , 2007 .

[11]  Christine M. Hrenya,et al.  Comparison of soft-sphere models to measurements of collision properties during normal impacts , 2005 .

[12]  H. Bechgaard,et al.  Controlled-Release Multiple-Units and Single-Unit Doses a Literature Review , 1978 .

[13]  M. Adams,et al.  Modelling collisions of soft agglomerates at the continuum length scale , 2004 .

[14]  R. E. García,et al.  Spheronization process particle kinematics determined by discrete element simulations and particle image velocimentry measurements. , 2014, International journal of pharmaceutics.

[15]  Stefan Heinrich,et al.  DEM–CFD modeling of a fluidized bed spray granulator , 2011 .

[16]  Y. S. Cheong,et al.  The coefficient of restitution of different representative types of granules , 2007 .

[17]  Milada Pezo,et al.  DEM/CFD analysis of granular flow in static mixers , 2014 .

[18]  S. Heinrich,et al.  The normal and oblique impact of three types of wet granules , 2011 .

[19]  S. Luding Cohesive, frictional powders: contact models for tension , 2008 .

[20]  M. Thommes,et al.  New Insights into the Pelletization Mechanism by Extrusion/Spheronization , 2010, AAPS PharmSciTech.

[21]  Stefan Heinrich,et al.  Coefficient of restitution for particles impacting on wet surfaces: An improved experimental approach , 2016 .

[22]  The influence of plate design on the properties of pellets produced by extrusion and spheronization. , 2012, International journal of pharmaceutics.

[23]  Ng Niels Deen,et al.  Numerical analysis of solids mixing in pressurized fluidized beds , 2010 .

[24]  Francesco Paolo Di Maio,et al.  DEM simulation of the mixing equilibrium in fluidized beds of two solids differing in density , 2008 .

[25]  Tawatchai Charinpanitkul,et al.  Analysis of solid particle mixing in inclined fluidized beds using DEM simulation , 2006 .

[26]  J. C. Williams,et al.  The properties of non-random mixtures of solid particles , 1969 .

[27]  Jürgen Tomas,et al.  Adhesion of ultrafine particles—A micromechanical approach , 2007 .

[28]  O. Molerus Über die Axialvermischung bei Transportprozessen in kontinuierlich betriebenen Apparaturen , 1966 .

[29]  L. Fan,et al.  Studies on multicomponent solids mixing and mixtures Part III. Mixing indices , 1979 .

[30]  Stefan Heinrich,et al.  A Discrete Element Study of Wet Particle-Particle Interaction During Granulation in a Spout Fluidized Bed , 2009 .

[31]  C. Thornton,et al.  A theoretical model for the stick/bounce behaviour of adhesive, elastic-plastic spheres , 1998 .

[32]  Yoshitsugu Muguruma,et al.  Numerical simulation of particulate flow with liquid bridge between / particles simulation of centrifugal tumbling granulator , 2000 .

[33]  A. Fasano Novel approaches for oral delivery of macromolecules. , 1998, Journal of pharmaceutical sciences.

[34]  Stefan Heinrich,et al.  Influence of liquid layers on energy absorption during particle impact , 2009 .

[35]  S. L. Rough,et al.  Stages in spheronisation: evolution of pellet size and shape during spheronisation of microcrystalline cellulose-based paste extrudates , 2015 .

[36]  Yuqing Feng,et al.  Discrete particle simulation of gas fluidization of particle mixtures , 2004 .

[37]  P. Cundall,et al.  A discrete numerical model for granular assemblies , 1979 .

[38]  S. Heinrich,et al.  Influence of coating and wetting on the mechanical behaviour of highly porous cylindrical aerogel particles , 2015 .

[39]  K. Sommer Mechanismen des Pulvermischens , 1977 .

[40]  Gavin K. Reynolds,et al.  An experimental study of the variability in the properties and quality of wet granules , 2004 .

[41]  P. Lacey,et al.  Developments in the theory of particle mixing , 2007 .

[42]  J. Bertrand,et al.  Powder mixing: Some practical rules applied to agitated systems , 1991 .

[43]  Suyog P. Sulake,et al.  Recent Advances in Granulation Techniques , 2014 .

[44]  J. Ooi,et al.  An experimentally validated DEM study of powder mixing in a paddle blade mixer , 2017 .

[45]  Kurt Liffman,et al.  Study of mixing in gas-fluidized beds using a DEM model , 2001 .

[46]  J Michael Newton,et al.  Gastric emptying of multi-particulate dosage forms. , 2010, International journal of pharmaceutics.

[47]  S. Heinrich,et al.  Breakage behaviour of spherical granulates by compression , 2005 .

[48]  François Bertrand,et al.  Large-scale numerical investigation of solids mixing in a V-blender using the discrete element method , 2008 .

[49]  Using the Discrete Element Method for Predicting the Mixing Behavior of Gravity Blenders in Different Operation Modes , 2012 .

[50]  Die Fokker‐Planck‐Gleichung zur Beschreibung von axialen Transport‐ und Mischvorgängen in Rohrreaktoren , 2013 .

[51]  P. Kleinebudde,et al.  Spheronisation mechanism of MCC II-based pellets , 2013 .

[52]  S. S. Muley,et al.  Extrusion–spheronization a promising pelletization technique: In-depth review , 2016 .

[53]  Stefan Heinrich,et al.  DEM simulations of amorphous irregular shaped micrometer-sized titania agglomerates at compression , 2015 .