ARR - Annual Report

Executive Summary

In the immediate future, work within this project will focus on disintegration model sensitivity analysis, model calibration and validation. The disintegration model will then be linked to an existing model for high shear granulation, and the process of inverse problem solving for the linked process-product model initiated.

Initial experimental method development is also presented. In this work, the relationship between granulation process parameters, internal granule structure and granule dissolution kinetics was studied. The results demonstrate the important role of granule porosity in granule dissolution, and provide important steer for the development of validation experiments for granule disintegration.

A preliminary parametric sensitivity analysis was conducted for the unified granule disintegration model, which investigated the effects of initial granule size, disintegrant particle size, initial granule porosity and disintegrant absorption ratios on granule size distributions and size evolution. The model was found to be sensitive to all four parameters, with faster disintegration promoted by increased granule size, decreased disintegrant particle size, lower initial porosity and increased absorption ratios.

This annual report summarises key progress toward the project aims made over the past 12 months. In particular, a mechanistic single granule model has been developed, which includes rates processes such as liquid penetration, liquid absorbance, swelling and stress build-up. This single granule model has been coupled with a population balance model, to enable the modelling of swelling driven breakage for populations of granules.

The aim of this project is to demonstrate the ability to link process and product models for wet granulation processes, and to initiate solution of the inverse problem, i.e. to determine the required process parameters and material properties to provide desired granule performance. A case study of granule disintegration/dispersion has been chosen as the product performance model for this work.

1. the lack of mechanistic models which relate granule structure and material properties to granule properties, and
2. the cooperative development of linked process and product models, to ensure essential parameters are modelled throughout the process and product.

While these performance criteria are typically the driving reason to granulate in the first place, we are still unable to confidently design granulation processes which optimise for desired product performance. There are several reasons for this, but two of the largest hurdles to overcome are:

The vast majority of granular products are granulated to produce some desired function and performance. This function may be improved flow, reduced dustiness, specific granule strengths and attrition resistance, or could be specific criteria for dispersion or dissolution.

Goals

1 compare with the formulation guidelines obtained from (1).

3. Apply these methods to simplified industrial dispersion by industrial partners and

• Local scale tribological measurements using AFM.

during flow (4D imaging)

• High resolution confocal microscopy to probe structural development in situ

which aspect of the particles or formulation controls the rheology

the nature of the stress during flow (elastic or viscous), which helps to identify

high frequency rheometry and superposition rheometry, which help identify

• Advanced rheological methods which allow for stress deconvolution such as

the rheological response of the such dispersions, focusing on

2. To further develop a limited number of rheological and structural tools to interrogate

control of shear thinning/thickening and the control of the thixotropic response.

within. The properties aimed for, after discussing with IFPRI members, are the

formulation guidelines to do “more with less” or simplifying formulations from

simple formulations a wide range of behaviors can be ”built in”, i.e. obtaining

changing the properties of the building blocks of the suspensions, so that even in

with near hard interactions, we can widen the range of rheological responses by

1. To explore how, moving away from model systems containing spherical colloids

Our goals within the IFPRI project are threefold

5. Preliminary experiment results for continuous crystallization with wet mill and recycle

4. Investigation of model-based crystallization design with milling for shape optimization

3. Investigation of the effect of recycle on crystal size

2. Investigation of the effect of recycle on purity

1. Development of the overall model of the integrated system consisting of the continuous crystallization cascade, wet mill, ideal classifiers and recycle

Achieved Deliverables

This year, the focus was on system integration both in simulation and experimentally. A one-dimensional (1D) model was used for process intensification and integration. A model for a cascade of multi-stage continuous crystallizers connected to a downstream wet mill and two ideal classifiers were developed and the effect of recycle on crystal size and purity was studied. An attainable region was found for crystal size by optimizing the process for feed, recycle and mill ratio and temperatures of the three crystallizers. A model was developed for tracking impurity in crystals and effect of recycle on impurity was investigated. Prior experience was used to correlate one dimensional (1D) crystallization model outcomes to bulk properties to use the 1D model for fast optimization of the process to obtain large crystals with short aspect ratio. This work poses an example to what must be considered and learned from experimental data to formulate process optimization routines or 2D model for more accurate shape control. Preliminary experiments were done on a small-scale integrated process including two crystallizers, a wet mill and use of recycle. A model for real classification process including separation efficiency was also proposed to later implement in the system and investigate its effect both through simulation and experiments.

This report summarizes the main achievements during the year 2021 of the project with the aim of developing process systems engineering approaches for improved crystal size, shape, and purity control during crystallization processes. The successful crystallization process and system design requires an interdisciplinary effort, which ranges from population balance model (PBM) development of the system concept, through efficient implementation of model equations to soft-sensor development, which is required for the model predictive control (MPC) design as well. This report gives a deeper insight into these interdisciplinary development efforts, which also highlights the achievable improvements enabled by the combination of process modeling, high performance process simulation and optimization.

Executive Summary

EXECUTIVE SUMMARY

2

geometry, where faster flows will be possible.

Behringer hopper for use in future experiments to test these observations in a very different

fluctuations emanating from the outer wall. Finally we have repaired and modified the IFPRIfunded

not only the roughness/smoothness of the wall (as expected), but also to the magnitude of force

this to be true. We have further observed that we can associate different amounts of wall slip to

conditions. After resolving some issues with sensitivity to changes in humidity, we have found

given set of particles, and test whether they were constant across use under different boundary

boundaries. This allowed us to measure the 3 nonlocal constitutive parameters (A; b; s) for a

both particle-dynamics and stress fields under controlled conditions for six different-roughness

As Year 6 comes to a close, we have used fully-developed experimental protocols to measure

properties.

on separating which flow properties are set by the particle properties, versus those set by the wall

and (2) use these parameters to predict flows in other geometries. Thus, our current work focuses

can we (1) make flow measurements in one geometry which determine the constitutive parameters

and apply NLR to real granular systems. We aim to establish that, for a given set of particles,

In Years 4-6 of this project, we aim to address current shortcomings in how to calibrate

(A; b; s), but that we must know the amount of slip at the wall from geometry-dependent measurements.

packing densities, particle sizes and shapes, and shear rates, using just 3 constitutive properties

In Years 1-3, we established that NLR successfully models granular flows across different

particle properties, and the boundary conditions at the walls.

particles). Doing this requires a quantitative understanding of which properties are set by both the

determine the constitutive parameters for use in predicting flows in other geometries (for the same

the aim is to make a set of flow measurements for a set of particles in one geometry, and then

intermittent, creeping, quasi-static, and intermediate flows. In order for these models to be useful,

set of particles, which then can be used to predict flow fields and stresses over a large range of

promise of permitting the determination of a small number of empirical parameters for a particular

been the development of various nonlocal rheologies [1–7]. These constitutive models hold the

In the field of granular rheology, one of the most promising advances of the past decade has

varying external stimuli to the often heterogeneous network structure.

influences on different length scales ranging from the dynamics of the bridges with

of capillary suspensions to specific requirements, it is important to understand the

and coalescence between adjacent bridges. Thus, to tailor the mechanical properties

related to the properties of the capillary bridges, such as bridge breaking

to networks formed via other attractive interactions where these differences are inherently

of particle networks based on capillary bridges posses unique properties compared

of a solids in a bulk liquid with an added secondary liquid. The structure

from particles that form a network based on capillary forces and are typically composed

systems, namely capillary suspensions. These capillary suspensions originate

many possible applications. Here, we focus on a special case of such liquid-liquidsolid

Liquid-liquid-solid systems are becoming increasingly common in everyday life with

Executive Summary

crystallization process.

the digital twin developed can be used for in silico investigation and digital design of the

measurements can be incorporated in the parameter estimation. We also demonstrate how

improvement in the 2D PBM model capability and investigate how different 2D CSD

proprietary active pharmaceutical ingredient. This year we also achieved significant

of a digital twin, based on both 1D and 2D PBM for a model crystallization system of a

size-dependent growth expression and parameter estimation formulation in the development

between parameters and confidence intervals. We demonstrated the benefits of the novel

enables faster convergence of the parameter estimation and decrease in inter-correlation

proposes to use a series of “intelligent” constraints in the optimization. The novel formulation

that has been used traditionally only for qualitative monitoring. The formulation also

formulation proposed incorporates semi-quantitave data from FBRM measurement, a tool

real experimental data to achieve a digital twin development. The novel parameter estimation

numerical solution approach, which is the critical enabling step to connect general models to

A major focus this year was to develop robust parameter estimation formulation and

kinetics and demonstrate the improved prediction ability of models using the new expression.

thermocycles. We also introduce novel formulations for modeling size-dependent growth

an important phenomenon when considering the design of crystallization processes with

agglomeration and breakage mechanisms, which can also be used to model de-agglomeration,

In this report we focus on further development of the generalized PBM model to include

combination of process modeling, high performance process simulation and optimization.

development efforts, which also highlights the achievable improvements enabled by the

(MPC) design as well. This report gives a deeper insight into these interdisciplinary

equations to soft-sensor development, which is required for the model predictive control

model (PBM) development of the system concept, through efficient implementation of model

system design requires an interdisciplinary effort, which ranges from population balance

shape control during crystallization processes. The successful crystallization process and

aim of developing process systems engineering approaches for improved crystal size and

This report summarizes the main achievements during the year 2020 of the project with the

Abstract

e.ects of various key DEM parameters – and map our course for the remainder of the project.

software for the comparison of PEPT and DEM data, and preliminary results regarding the main

this Report, we outline the progress made so far – including the development of novel analysis

of Birmingham, will provide the central pillar of the aforementioned Best Practice document. In

This comparative analysis, supplemented by additional data provided by the team at the University

which the simulations methods employed are capable of recreating the systems’ true dynamics.

Particle Tracking (PEPT) facility, allowing a rigorous, quantitative assessment of the degree to

to detailed experimental data produced using the University of Birmingham’s Positron Emission

industrial relevance, under a variety of conditions. The simulations produced will be compared

a set of simulations modelling two distinct experimental set-ups, each chosen due to its direct

of particulate systems. Each company involved in the project has been charged with producing

several industrial sectors with a shared interest in modelling and thus predicting the dynamics

order to develop such a Best Practice, we are working alongside a number of companies spanning

the application of discrete element method (DEM) simulations to industrial process equipment. In

The ultimate goal of the IFPRI Round Robin is to develop an industry standard Best Practice for

Executive Summary

validate the results.

investigated particle and filter cake properties. Laboratory tests of the integral parameters

the local contact angle within the cake structure could be demonstrated on many of the

suspension, the wetting behavior could be precisely adjusted. The influence of changes in

with the mother liquor. By changing the ethanol content of the otherwise aqueous

Al2O3 (alumina) and CaSiO3 (wollastonite) particles were filtered at different combinations

Varying the wettability served as a parameter study. For this purpose hydrophobic coated

along the wetting line of the hydraulic isolated liquid areas within the pore space.

analysis of wet filter cakes allowed the measurement of the local contact angle distribution

coordination number, pore-to-pore relationships and the tortuosity of the filter cake. An

Detailed analysis of the tomographic data provided pore size distributions, the particle

filter cakes were determined and compared with results of standard measurement methods.

step, simple parameters such as total porosity or particle size distribution of the scanned

Commercially available software as well as specially developed code was used. In a first

sharpened and segmented by means of image processing before further analysis.

cake structure followed. The image data sets of the tomography were denoised, smoothed,

and measured in the µCT. After the measurement, a morphological analysis of the filter

The proof of comparability was followed by analyses of filter cake built in the in situ cell

the laboratory (Laboratory VDI Nutsch) and in the downscaled in situ Nutsch filter.

situ experiment to the larger scale. The proof was provided by validation experiments in

by preliminary investigations, which proved the transferability of the results from the in

during and after the process. The direct measurements in the µCT (in situ) were preceded

in µCT in order to examine the filtration process and the filter cakes built up without change

For this purpose, it was necessary to downscale a standard pressure Nutsch for direct use

filter cake, i.e. to obtain spatially resolved data instead of integral parameters.

The main objective was to obtain local information from the inside of the

the process-relevant structural effects of the filter cakes can be investigated nondestructively.

cake structure and other relevant filtration properties. Using X-ray computed tomography,

The aim of this project was to investigate the influence of particle properties on the filter

parameters such as the filtration resistance.

of the filter cake, such as its pore size distribution and tortuosity, and associated process

particles affect the structure of the filter cake. Associated with them are resulting properties

belonging fluid and particles. Size, shape, wetting behavior and other properties of the

Filtration properties are strongly dependent on the properties of the suspension, the

systems.

in the rolling mode to fully cascading ows consistent with industrial comminution

successfully scales up mixing con gurations spanning slowly rotated drums operated

Mixing Mechanisms

three mixing mechanisms are then achieved via the Entrainment number. The theory

dominated, and (iii) intermediate (both shear and advection). Scale-up rules of the

that classify mixing into three categories: (i) shear dominated, (ii) advective

Focussing on shear and advective mixing, we isolate the corresponding energy signatures

forced-to-free entrainment|The Entrainment Number.

the governing equations yields a set of dimensionless numbers, including the ratio of

and basal interface) and full velocity eld. Subsequent non-dimensionalisation of

(PEPT) measurements con rms the successful recovery of bed geometry (free surface

transient and non-uniform ow conditions. Positron Emission Particle Tracking

free surface e z(x), basal interface z e (x), and depth-averaged velocity u(x) under arbitrary

subsequent balance of mass, momentum and energy yields di erential equations to the

dense, viscoplastic granular rheology of (da Cruz et al., 2005; GDR MiDi, 2004), a

spanning rolling-to-fully-cascading ow regimes. Starting with the linearised form of

of rotating drum ows that facilitates scale-up of the dominant mixing mechanisms

The Entrainment Number (^ !)|from a fundamentally-derived granular ow model

In our third phase of the project we identify a suitable dimensionless number|

Executive Summary

Executive Summary

This project seeks to develop physically realistic models for atomization processes relevant to particle production, such as in spray-drying processes, with a focus on high viscosity and non-Newtonian fluid atomization. The goals of this work are to generate a spray database and to develop understanding and correlations for the accurate pilot-to-production scaleups. We have divided the work to focus on two nozzle types: pressure-swirl, and two-fluid nozzles. The followings are achieved in the present reporting period.

Pressure‐swirl:

• Completed testing of Fine Spray nozzles with several different fluids with varying viscosities. The droplet size distributions, closeup images of the atomization zone, and other statistics are obtained and reported.
• A correlation for SMD has been found using pressure-based Weber number and Reynolds number.
• The above correlation does not work well for sprays formed by small orifice nozzles using high viscosity fluid (60 cps). This was found to be due to change in the atomization mechanism for such cases. Atomizing very high viscosity fluid (60 cps) with small orifice nozzles may result in very large SMD, indicating a poor atomization quality. This is due to significant pressure loss across small orifices using high viscosity liquids.
• The above correlation has also been tested with experimental data by other researchers that have used different nozzle designs.