Computer simulation of granule microstructure formation

The diagenesis (porous microstructure evolution) of granules formed by a layering growth mechanism in a wet granulation process has been modelled. The model includes the packing of primary particles with a given size and shape distribution, and the deposition, spreading, and solidification of binder droplets within the growing granule. The dependence of granule porosity on the binder/solids ratio, primary particle size and morphology, and the rates of binder spreading and solidification has been investigated. The results are presented in the form of structure maps relating volume-averaged microstructure parameters with dimensionless groups including the ratio of droplet spreading and solidification times and the mean time between particle collisions. These graphs can guide the selection of process operating conditions or formulation ingredient properties required to obtain a particular granule microstructure.

[1]  František Štěpánek,et al.  Computer-Aided Product Design: Granule Dissolution , 2004 .

[2]  J. Brock,et al.  Volume tracking of interfaces having surface tension in two and three dimensions , 1996 .

[3]  Gabriel I. Tardos,et al.  Computer simulation of wet granulation , 2000 .

[4]  N. Alleborn,et al.  Spreading and sorption of a droplet on a porous substrate , 2004 .

[5]  A. Clarke,et al.  Spreading and Imbibition of Liquid Droplets on Porous Surfaces , 2002 .

[6]  Omar Matar,et al.  Droplet spreading, imbibition and solidification on porous media , 2006, Journal of Fluid Mechanics.

[7]  Colin Thornton,et al.  Numerical simulations of agglomerate impact breakage , 1999 .

[8]  Wilfried Rähse,et al.  Product Design – The Interaction between Chemistry, Technology and Marketing to Meet Customer Needs , 2003 .

[9]  Steven A. Cryer,et al.  Observations and process parameter sensitivities in fluid‐bed granulation , 2003 .

[10]  F. Štěpánek,et al.  Microstructure and transport properties of wet poly-disperse particle assemblies , 2005 .

[11]  J. Litster,et al.  Drop penetration into porous powder beds. , 2002, Journal of colloid and interface science.

[12]  Eric Favre,et al.  Chemical Product Engineering: Research and Educational Challenges , 2002 .

[13]  J. Kuipers,et al.  Discrete element modelling of fluidised bed spray granulation , 2003 .

[14]  Pierre M. Adler,et al.  GEOMETRICAL AND TRANSPORT PROPERTIES OF RANDOM PACKINGS OF SPHERES AND ASPHERICAL PARTICLES , 1997 .

[15]  A. Yu,et al.  Packing of multi-sized mixtures of wet coarse spheres , 2003 .

[16]  Torben Schaefer,et al.  Effects of droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[17]  Ain A. Sonin,et al.  Motion and arrest of a molten contact line on a cold surface: An experimental study , 1997 .

[18]  Ka Yip Fung,et al.  Product-centered processing: Pharmaceutical tablets and capsules , 2003 .

[19]  B. J. Ennis,et al.  Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review , 2001 .

[20]  Anuraag R. Kansal,et al.  Computer generation of dense polydisperse sphere packings , 2002 .

[21]  Gabriel I. Tardos,et al.  Evolution and structure of drying material bridges of pharmaceutical excipients: studies on a microscope slide , 2003 .