Understanding granular mixing to enhance coating performance in a pan coater: Experiments and simulations

Abstract The knowledge of the particle flow and mixing in a pan coater is critical to optimize the design and operation of coating equipment. Mixing is an important but poorly understood aspect of coating of pharmaceutical dosage forms (tablets). Our study focuses on the fundamental mechanisms of granular flow and mixing and their relationship to the coating performance. A quantitative method is developed and validated to characterize the mixing process throughout the mixing vessel. This method is used to establish a baseline determination of mixing homogeneity as a function of various mixing conditions. White and red non-pareils of 5–6 mesh size are loaded in the ellipsoid pan coater to check the effect of initial loading (side–side and front–back), fill level, orientation of the vessel and the vessel speed on granular mixing. Video-imaging and discrete-pocket samplers are used to quantify mixing and to finally estimate the optimal operating conditions. DEM (Discrete Element Method) based numerical model was also developed to study the effect of granular mixing in a pan coater. When the axis of rotation of the mixer is horizontal (no tilt), slower axial dispersion is observed in both the experiments and simulations, than the radial convection. However, tilt enhances axial mixing, and faster axial mixing is seen for higher tilt angles from the horizontal. The speed of the rotating vessel has a nominal effect on the rate of mixing in a coating pan, as observed from the experimental and simulation studies. Moreover, fill level has no significant effect on the rate of mixing. Coating experiments are performed in the pan coater where white non-pareils being coated by spraying Opadry II solution. DEM simulation of coating is performed with post processing particle dynamics data. The effects of various operational and spray parameters are determined on the coating performance. Optimal coating performance is attained at an optimal mixing condition.

[1]  Clive E Davies,et al.  Avalanching flow of cohesive powders , 2006 .

[2]  J. Bridgwater,et al.  A case study of particle mixing in a ploughshare mixer using Positron Emission Particle Tracking , 1998 .

[3]  B Buisson,et al.  A model of surface renewal with application to the coating of pharmaceutical tablets in rotary drums , 2003 .

[4]  Fernando J. Muzzio,et al.  A study of the mixing and segregation mechanisms in the Bohle Tote blender via DEM simulations , 2006 .

[5]  J. K. Brimacombe,et al.  Experimental study of transverse bed motion in rotary kilns , 1983 .

[6]  Thompson,et al.  Granular flow: Friction and the dilatancy transition. , 1991, Physical review letters.

[7]  Fernando J. Muzzio,et al.  Cohesive effects in powder mixing in a tumbling blender , 2006 .

[8]  Fernando J. Muzzio,et al.  Simulation of flow and mixing of particles in a rotating and rocking cylinder , 1998 .

[9]  M. E. Aulton,et al.  The behavior of film coating droplets on their impingement onto uncoated and coated tablets , 1995 .

[10]  Carl Wassgren,et al.  Inter-tablet coating variability: Residence times in a horizontal pan coater , 2008 .

[11]  A. Yu,et al.  Microdynamic analysis of particle flow in a horizontal rotating drum , 2003 .

[12]  Eiichi Fukushima,et al.  Nuclear magnetic resonance as a tool to study flow , 1999 .

[13]  Kenji Yamane,et al.  Computer Simulation of Tablet Motion in Coating Drum , 1995, Pharmaceutical Research.

[14]  W. O. Mancoff.  Film coating compressed tablets in a continuous process , 1998 .

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

[16]  Otis R. Walton,et al.  Numerical simulation of inclined chute flows of monodisperse, inelastic, frictional spheres , 1993 .

[17]  Richard Turton,et al.  Modeling weight variability in a pan coating process using Monte Carlo simulations , 2006, AAPS PharmSciTech.

[18]  R. Turton,et al.  The Prediction of Variability Occurring in Fluidized Bed Coating Equipment. I. The Measurement of Particle Circulation Rates in a Bottom-Spray Fluidized Bed Coater , 2000, Pharmaceutical development and technology.

[19]  J. Green,et al.  The legacy of neglect in the US , 1994 .

[20]  F. Muzzio,et al.  Mixing dynamics in catalyst impregnation in double-cone blenders , 1999 .

[21]  Tablet-to-tablet variation of drug content of sugar-coated tablets containing drug in the sugar coat. , 1970, Journal of pharmaceutical sciences.

[22]  Richard Turton,et al.  Simulation of particle movement in a pan coating device using discrete element modeling and its comparison with video-imaging experiments , 2006 .

[23]  Kirk E. Wilson,et al.  The Influence of Tablet Shape and Pan Speed on Intra-tablet Film Coating Uniformity , 1997 .

[24]  G. H. Ristow,et al.  Dynamics of granular materials in a rotating drum , 1996 .

[25]  J. Zhou,et al.  Determination of Tablet Coating Distribution by Deconvolution of Uncoated and Coated Tablet Weight Distributions , 1996, Pharmaceutical Research.

[26]  R. Chang,et al.  The Effect of Run Time on the Inter-Unit Uniformity of Aqueous Film Coating Applied to Glass Beads in a Hi-Coater , 1995 .

[27]  Fernando J. Muzzio,et al.  Quantitative characterization of mixing of dry powders in V‐blenders , 1998 .

[28]  Collision-induced friction in the motion of a single particle on a bumpy inclined line. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[29]  R. L. Braun,et al.  Viscosity, granular‐temperature, and stress calculations for shearing assemblies of inelastic, frictional disks , 1986 .

[30]  Carl Wassgren,et al.  Inter-tablet coating variability: Tablet residence time variability , 2009 .

[31]  S. Luding.  Stress distribution in static two-dimensional granular model media in the absence of friction , 1997 .

[32]  Troy Shinbrot,et al.  Experimentally validated computations of flow, mixing and segregation of non-cohesive grains in 3D tumbling blenders , 2000 .

[33]  F J Muzzio,et al.  Sampling and characterization of pharmaceutical powders and granular blends. , 2003, International journal of pharmaceutics.

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

[35]  R C Rowe,et al.  A photometric analysis of tablet movement in a side‐vented perforated drum (Accela‐Cota) , 1985, The Journal of pharmacy and pharmacology.

[36]  B. Buchanan,et al.  Use of Near-Infrared Spectroscopy to Evaluate an Active in a Film Coated Tablet , 1996, Pharmaceutical Research.

[37]  Julio M. Ottino,et al.  Transverse flow and mixing of granular materials in a rotating cylinder , 1997 .