A population balance model for high shear granulation

In a previous paper, Hoornaert et al. (Powder Technol. 96 (1998); 116-128) presented data from granulation experiments performed in a 50 L Lodige high shear mixer. In this study that same data was simulated with a population balance model. Based on an analysis of the experimental data, the granulation process was divided into three separate stages: nucleation, induction, and coalescence growth. These three stages were then simulated separately, with promising results. it is possible to derive a kernel that fit both the induction and the coalescence growth stage. Modeling the nucleation stage proved to be more challenging due to the complex mechanism of nucleus formation. From this work some recommendations are made for the improvement of this type of model.

EFFECT OF IMPELLER DESIGN ON PRODUCT HOMOGENIETY IN HIGH SHEAR WET GRANULATION

Design of small mixer impellers is not tailored for granulation as they are designed for a wide range of processes. The Kenwood KM070 was employed as a standard apparatus to undertake this investigation. Five different impeller designs were used, possessing different shapes and surface areas. The aim of this research was to evaluate the performances of these impellers to provide
guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as the binder.
The efficacy of respective granulates was measured by adding an optically
sensitive tracer.This was used to determine powder concentrations
within various regions of the granulator. It was found that impeller design influenced the homogeneity of the granules; and therefore can affect final product performance.

Effect of Impeller Design on Homogeneity, Size and Strength of Pharmaceutical Granules produced by High Shear Wet Granulation

Small mixer impeller design is not tailored for granulation because impellers are intended for a wide range of processes. The aim of this research was to evaluate the performances of several impellers to provide guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as a binder. A Kenwood KM070 mixer was used as a standard apparatus and five impeller designs with different shapes and surface areas were used. The efficacy of granulate formation was measured by adding an optically sensitive tracer to determine variations in active ingredient content across random samples of granules from the same size classes. It was found that impeller design influenced the homogeneity of the granules and therefore can affect final product performance. The variation in active ingredient content across granules of differing size was also investigated. The results show that small granules were more potent than larger granules.

Effect of batch size on mechanical properties of granules in high shear granulation

The flow patterns in a high shear granulator depend on the fill volume. For example, DEM simulations reported by Terashita et al. [1] show that fill volume affects the velocities and kinetic energies of the particles. It also influences the granule size distribution [2]. Here the effects on the properties of the granule are described. The total mass of the granulate material was varied without changing the other variables such as impeller speed, granulation time and liquid to solid ratio. The resulting mechanical properties, such as strength, yield stress and Young's modulus, of the granules were measured. For the materials studied in the current work, increasing the fill factor (batch size) increased the values of these material parameters. This could be explained by the relative increase in the number and intensity of collisions between the particles, when the size of a batch was increased, leading to smaller porosities. (c) 2010 Elsevier B.V. All rights reserved.

GPVI levels in platelets: relationship to platelet function at high shear

We have investigated the density of the collagen receptors glycoprotein VI (GPVI) and alpha(2)beta(1) on human platelets and their relationship to polymorphisms within the GPVI gene. GPVI levels varied 1.5-fold and showed a weak correlation (r = 0.35) with the levels of alpha(2)beta(1), which varied 3-fold. GPVI genotype had a significant effect on receptor levels with carriers of the proline 219 allele (approximately 22% of the population) having 10% lower GPVI levels than the more common serine homozygotes. GPVI and alpha(2)beta(1) levels were found to be significantly decreased on platelets from patients with myeloproliferative disorders (MPDs). In both the MPD and the control group, GPVI levels were found not to affect platelet function under high shear in whole blood. Similarly murine platelets that express up to 5-fold lower levels of GPVI showed no significant difference than controls in thrombus formation on a high-density collagen-coated surface. However platelets lacking the GPVI/Fc receptor gamma-chain (FcR gamma-chain) complex or a functional FcR gamma-chain (immunoreceptor tyrosine-based activation motif [ITAM] point mutant) exhibited severely abrogated thrombus formation at 800 s(-1) and 1500 s(-1). These results demonstrate that GPVI levels are tightly controlled and play a critical role in thrombus formation on collagen; nevertheless, a range of receptor densities can support platelet function under high shear. (C) 2003 by The American Society of Hematology.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. © 2012 Elsevier B.V. All rights reserved.

Optimisation of high shear granulation of multicomponent fertiliser using response surface methodology

This work describes a novel method of producing multicomponent fertiliser granules using high shear granulation. The granulation process was optimised using the response surface methodology technique. The variables used in the optimisation process include granulation time, batch size, impeller speed and binder concentration. Granulation time, binder concentration and interaction between the batch size and granulation time were found to be the main factors affecting the granule median size. The product yield is mainly influenced by granulation time and binder concentration. The interaction between the impeller speed and batch size also have a significant influence on the product yield. Product yield (2-4 mm) of approximately 60% could be obtained with high sphericity and granule strength (> 0.5 MPa). A low product recycle ratio of about 2:3 can be obtained at the optimised process conditions, compared to typical recycle rations of 6:1 which are obtained in typical fertiliser plants. © 2012 Elsevier B.V. All rights reserved.

Alternative method for producing organic fertiliser from anaerobic digestion liquor and limestone powder:High Shear wet granulation

Generally, the solid and liquid fractions (digestate) from Anaerobic Digestion (AD) energy production are considered as waste. This has a negative impact on the sustainability of AD processes because of the financial outlay required to treat digestate before being discharged into municipal water treatment plants or natural water bodies. The main aim of this research was to investigate feasibility of producing an organic fertiliser using anaerobic digestate and limestone powders as the raw materials employing a high shear granulation process. Two-level factorial experimental design was used to determine the influence of granulation process variables on, the strength, resistance to attrition and yield of the granules. It was concluded from the study that it is technically feasible to produce organic fertiliser granules of acceptable strength and product yield. Increasing the liquid-to-solid ratio during granulation leads to increased granule strength and better product yield. Although the strength of the granules produced was lower than typical strength of commercial synthetic fertiliser granules (about 5 to 7. MPa), this could be improved by mixing the digestate with a polymeric binder or coating the particles post granulation. © 2012 Elsevier B.V.

The variability in nutrient composition of Anaerobic Digestate granules produced from high shear granulation

This study investigates the production of organic fertilizer using Anaerobic Digestate (as a nutrient source) and limestone powder as the raw materials. A two-level factorial experimental design was used to determine the influence of process variables on the nutrient homogeneity within the granules. Increasing the liquid-to-solid ratio during granulation resulted in increased granule nutrient homogeneity. Increasing the processing time and the impeller speed were also found to increase the nutrient homogeneity. In terms of nutrients release into deionized water, the granules effectively released both potassium and phosphate into solution. © 2012 Elsevier Ltd.

Effect of impeller speed on mechanical and dissolution properties of high-shear granules

Impeller speed is one of the most crucial process variables that affect the properties of the granules produced in a high-shear granulator. Several reports can be found in literature that discuss the influence of impeller speed on the granules size. For instance some researchers like Knight report an increase of granule size with impeller speed [1] and [2], while others (Scheaefer et al. and Ramaker et al.) observed a decrease of granules size with increasing impeller speed [3] and [4]. However there is limited work reported in literature on the effect of the impeller speed on the mechanical properties of granules. Mechanical properties are important as they affect the performance of the granules on the other downstream process such as transportation and handling. The work reported here serves to address the missing in knowledge gap regarding the influence of impeller speed on mechanical properties granules. How the granulation system responds to the changes in the impeller speeds depends on binder that is used in the process. For this reason the two extreme cases, of a low viscosity binder system and high viscosity binder system are considered in this research. For low viscosity binder system it was observed that the granule size decreased with increasing impeller speed whilst for the high viscosity binder system the opposite was observed by Knight [1]. The granule strength, the Young's modulus and yield strength of the high viscosity granules increased with increasing impeller speed where as the opposite trends were observed for the low viscosity binder granules.

Development of a value-added soil conditioner from high shear co-granulation of organic waste and limestone powder

This paper reports on a technical feasibility study of the production of organo-mineral fertiliser from the co-granulation of limestone powders with tea waste. The results from this preliminary study show that the co-granulation of tea waste provided an alternative method of waste recovery, as it converts the waste into a value-added product. Fertiliser granules were successfully produced from various compositions of limestone and tea waste. The effect of tea waste concentration on granule strength was analysed; the granule strength
was in the range 0.2 to 1.8 MPa depending on powder composition; increasing the tea waste mass fraction resulted in a reduction in granule strength.Varying the teawaste to limestone ratio also influenced the compressibility of the granules; the granules compressibility increased with increasing tea waste mass fraction. It was further found that increasing the mass fraction of tea waste in the binary mixture of powder reduced the granule median size of the batch.

Influence of fill factor variation in high shear granulation on the post granulation processes: Compression and tablet properties

This paper describes an investigation of the effect of fill factor; on the compaction behaviour of the granules during tableting and hence mechanical properties of tablets formed. The fill factor; which is the ratio of volume of wet powder material to vessel volume of the granulator, was used as an indicator of batch size. It has been established previously that in high shear granulation the batch size influences the size distribution and granule mechanical properties [1]. The work reported in this paper is an extension to the work presented in [1], hence granules from the same batches were used in production of tablets. The same tabletting conditions were employed during tabletting to allow a comparison of their properties. The compaction properties of the granules are inferred from the data generated during the tabletting process. The tablet strength and dissolution properties of the tablets were also measured. The results obtained show that the granule batch size affects the strength and dissolution of the tablets formed. The tablets produced from large batches were found to be weaker and had a faster dissolution rate. The fill factor was also found to affect the tablet to tablet variation of a non-functional active pharmaceutical ingredient included in the feed powder. Tablets produced from larger batches show greater variation compared to those from smaller batches.

High shear granulation of binary mixtures: Effect of powder composition on granule properties: Effect of powder composition on granule properties

The granular product being designed in this work required the use of two different powders namely limestone and teawaste; these materials have different bulk and particle densities. The overall aim of the project was to obtain a granular product in the size range of 2 to 4. mm. The two powders were granulated in different proportions using carboxymethylcellulose (CMC) as the binder. The effect of amount of binder added, relative composition of the powder, and type of teawaste on the product yield was studied. The results show that the optimum product yield was a function of both relative powder composition and the amount of binder used; increasing the composition of teawaste in the powder increased the amount of binder required for successful granulation. An increase in the mass fraction of teawaste in the powder mix must be accompanied by an increase in the amount of binder to maintain the desired product yield.