Multi-scale modeling of high-shear granulation

Daniel A Pohlman, Purdue University

Abstract

High shear wet granulation is a particle design process used to increase the size of a primary powder material through the addition of liquid binder. This thesis focuses on the multi-scale nature of high-shear granulation in order to understand behavior changes due to coupled consolidation and coalescence as well as operational changes that occur during the scale up of horizontal ploughshare mixer granulators. The methodology relied on a micro-scale model for coalescence, a meso-scale model to describe flow within the granulator and a macro-scale population balance to describe the whole system.^ A physically based coalescence model was adapted to the 3D population balance model framework as a function of the granule internal property coordinates: solid volume, liquid volume, and gas volume. An empirical correlation was used to describe granule mechanical properties based on measured peak flow stress as a function of granule composition and strain rate. In this case study a well characterized but complex industrial formulation was used. The model predicts that rebound collision will occur early in the granulation and cause densification. As these granules consolidate and become stronger there is some critical composition at which the internal pore space is saturated with liquid and a film comes to the surface. This micro-scale model is able to predict induction time based on understanding of consolidation. The model is validated by semi-quantitative comparison with experimental studies in a 50 L horizontal axis high shear granulator. Measurements of the size, porosity and morphology are used to verify rate process mechanisms over the course of the wet granulation process. The class of growth behavior and the length of the induction time are correctly predicted by the micro-scale model.^ Scale up experiments were conducted to validate and test the predictions of the compartment model approach. Traditional scaling rules of constant impeller Froude number and constant impeller tip speed were shown to be ineffective at producing similar granule size distributions or porosities across granulator volumes of 10L, 20L and 50L. Scale of the granulator had a large effect on product attributes and overall granulation behavior. At the 10L scale the extent of breakage was limited and product size distributions remained broad. At the 20L scale the distributions narrowed slightly compared to the 10L and the rate of consolidation increased. The 50L product properties had a narrow, desirable size distribution. The breakage and consolidation at the 50L scale broke the granular clumps and consolidation rate was again higher that at the 20L. The 50L granulator’s behavior transitioned to granule growth showing that traditional scaling rules may not even predict overall granulation behavior. Because this change in behavior was due to the high extent of consolidation, a new scaling rule for the consolidation rate was developed for horizontal mixers across these scales. This is the first time a scaling rule has been determined across granulator scales with the ability to predict dramatic changes due to complex consolidation coupled coalescence. ^ A two compartment population balance model was developed to physically represent the flow heterogeneity and rate process segregation that occurs in a horizontal high-shear mixer granulator. It was composed of two zones, a circulation zone that represents the bulk of the mixer, and a breakage zone representing the high-speed chopper knives that are used to break up clumps and large granules. Flow between the two zones was determined by a heuristic and rules for model scale up were developed. The model includes expressions for consolidation coupled coalescence, and consolidation of granules in the circulation zone, and breakage is modeled in the breakage zone. This two compartment 2D population balance model predicted scale up distributions well from the 10L to 20L and 50L granulator experiments.^ The compartmental population balance model is a useful tool that can be applied to different scales and types of granulators by configuring the appropriate meso-scale compartmental arrangement, and determining the which rate processes belong in each compartment.^

Degree

Ph.D.

Advisors

James D. Litster, Purdue University.

Subject Area

Chemical engineering|Pharmaceutical sciences

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