Growth kinetics and mechanism of wet granulation in a laboratory-scale high shear mixer: Effect of initial polydispersity of particle size

Abstract The effect of initial polydispersity of particle size (unimodal versus bimodal distribution) and binder characteristics on the growth kinetics and mechanism of wet granulation was studied. Wet granulation of pharmaceutical powders with initial bimodal particle size distribution (PSD) presented growth kinetics consisting of two stages: fast growth followed by slow growth. The fast stage is controlled by the amount of binder and high probability of coalescence due to the collisions of small and large particles. The second stage is characterized by slow agglomeration of powder mixtures with water content 13.6% v/w, and slow breakage of powder mixtures with water content of 9.9% and 11.7% v/w. The wet granulation of powders with initial unimodal PSD exhibited slow growth kinetics consisting of one stage, since similar particle sizes do not promote agglomeration. The experimental results were better described by a population balance equation using a coalescence kernel that favors growth rate by collision between small and large particles. In general, the probability of a successful collision increased with higher size difference between particles, smaller particle size, and higher binder content.

[1]  James D. Litster,et al.  Growth regime map for liquid-bound granules , 1998 .

[2]  P. Vonk,et al.  Description of agglomerate growth , 1998 .

[3]  James D. Litster,et al.  Population balance modelling of drum granulation of materials with wide size distribution , 1995 .

[4]  Ulrich Nieken,et al.  Modeling and simulation of crystallization processes using parsival , 2001 .

[5]  Torben Schæfer,et al.  Melt Granulation in A Laboratory Scale High Shear Mixer , 1990 .

[6]  S. Badawy,et al.  Effect of starting material particle size on its agglomeration behavior in high shear wet granulation , 2004, AAPS PharmSciTech.

[7]  Kinetics of iron ore sinter feed granulation , 1990 .

[8]  Michael J. Hounslow,et al.  Tracer studies of high‐shear granulation: II. Population balance modeling , 2001 .

[9]  Sotiris E. Pratsinis,et al.  Agglomeration behaviour of powders in a Lödige mixer granulator , 1998 .

[10]  Torben Schæfer,et al.  Granulation in high speed mixers. I: Effects of process variables during kneading , 1983 .

[11]  Alvaro Realpe,et al.  Pattern recognition for characterization of pharmaceutical powders , 2006 .

[12]  P. Mort,et al.  Critical parameters and limiting conditions in binder granulation of fine powders , 1997 .

[13]  Bryan J. Ennis,et al.  The influence of viscosity on the strength of an axially strained pendular liquid bridge , 1990 .

[14]  J. Litster,et al.  Influence of the material properties of iron ore sinter feed on granulation effectiveness , 1988 .

[15]  J. N. Michaels,et al.  Effect of primary particle size on granule growth and endpoint determination in high-shear wet granulation , 2000 .

[16]  B. J. Ennis,et al.  A microlevel-based characterization of granulation phenomena , 1991 .

[17]  Michael J. Hounslow,et al.  Studies of fluid bed granulation in an industrial R&D context , 2005 .

[18]  Jpk Seville,et al.  The effect of binder viscosity on particle agglomeration in a low shear mixer/agglomerator , 2000 .

[19]  A. A. Adetayo,et al.  Unifying approach to modeling granule coalescence mechanisms , 1997 .

[20]  H. Kristensen,et al.  Granulation in high speed mixers. III: Effects of process variables on the intragranular porosity , 1984 .

[21]  James D. Litster,et al.  Growth regime map for liquid-bound granules: further development and experimental validation , 2001 .