ARR - Annual Report

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.

Executive Summary

driven model for granulation.

for granulation, and the application of inverse methods to create a product performance

incorporates the development, validation and integration of process and product models

A research plan for the remaining three years of the project is presented. This plan

characterisation of feed materials and granular products.

models, however this initial experimentation has emphasised the need for careful

will take place after critical decisions are made on choices of product and process

development for granulation and granule dissolution. Full methodology development

Also presented within this report is preliminary experimental methodology

absence of disintegration.

dispersion model, and the second a model for drug dissolution from granules in the

two potential product models presented here for use in this project. The first is a granule

available to describe these mechanisms. This review has informed the development of

disintegration and dissolution, and also includes a review of the mathematical models

review incorporates the current state of knowledge on the mechanisms of compact

behaviour, culminating in the literature review presented in this report. This literature

survey of the literature on granule, tablet and compact disintegration and dissolution

of Granular Products. Focus has been placed in this first year of the project on a critical

This report provides a summary of the progress of the project Model Assisted Design

address this need.

product models to enable performance driven process design. The aim of this project to

develop improved performance models for granular products, and to link these with

models have received less attention than process models, and there is a clear need to

not describe the performance of the products being produced. Product performance

outputs of these models are typically limited to one or two particle attributes, and do

processes. This is an exciting and welcome development for the field, however the

process design. Process models are increasingly being developed and used for these

and laborious experimentation, due to a lack of knowledge and predictive tools for

Traditionally, the design and scale-up of granulation processes has involved expensive

tool that predicts relative growth rates and crystal morphology of solution-grown faceted crystals [5].

into ADDICT (Advanced Design and Development of Industrial Crystallization Technology), an engineering

in the literature for validation. Once we have established effective models, we will look to incorporate them

considered in the context of KMC simulations for model development, and compared to experimental values

the growth-inhibiting effect of impurities, such as step pinning and spiral pinning. These mechanisms are

for desolvation and attachment/detachment works. Various mechanisms have been proposed to explain

centrosymmetric organic crystal growth. Rare event rates are determined as functions of energetic barriers

for growth inhibition. We employ Kinetic Monte Carlo (KMC) methods to simulate the time evolution of

ne to examine experimentally in real time. Thus, we use simulations to study the proposed mechanisms

Impurities affect growth kinetics at the scale of kink attachment and detachment events, which are too

and hence affect crystal morphology and size.

process and to develop theoretical models for the mechanisms by which impurities influence crystal growth

The goal of this project is to investigate the effect of impurities or `imposter molecules' on the crystal growth

are more representative of realistic conditions. One such non-ideality involves the presence of impurities.

equal surfaces). There is interest in studying crystal systems in which non-idealities are introduced, as these

systems i.e., Kossel crystals with a single centrosymmetric growth unit (simple cubic single molecules with

mechanistic modelling of crystallization. Crystallization of organic molecules is well understood for ideal

Given the ubiquity of crystal growth in industrial processes, there is substantial demand for predictive and

such as OLEDs [3] and for altering the impact sensitivity of energetic materials such as RDX and HMX [4].

crystallization is desirable for varying electrical and optical properties in the field of electronic materials

importance for developing catalysts with tailored surfaces to maximize active sites [2]. Furthermore, tuning

to selectively formulate specific crystal habits for optimal bioperformance [1]. Crystal engineering is also of

a structured solid state. Pharmaceutical companies often crystallize APIs in the form of organic molecules

Crystallization is commonly used in industrial processes to convert solute molecules dissolved in solvent to

Abstract

compare with the formulation guidelines obtained from (1).

3. Apply these methods to simpli ed industrial dispersion by industrial partners and

• Local scale tribological measurements using AFM.

during ow (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 ow (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 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

project and more globally within our groups are threefold

(all started in 2020) being the graduate students involved. Our goals within the IFPRI

Jan Vermant, with C. Hsu (graduated in 2020), V. Niggel, F. Muller, and P. Lehercy

The work at ETH Zurich represents a combined e ort of the labs of Profs. Lucio Isa and

Executive Summary

Type and dosage of grinding aid.

Mill geometry and design;

Process parameters;

Product transport behavior;

Product breakage characteristics;

consumption in relation to:

dynamical population balance model predicting product size distribution and energy

Moreover, the continuous grinding process modelling approach is being structured as a

stressing and transport independently.

grinding. The results also confirm the necessity of describing the phenomena of powder

behavior, although beneficial for continuous processing, does not guarantee an effective

but with good results for milling efficiency for both materials. It is clear that improved flow

flowability for both materials. The glycol presented negligible effect on powder flowability,

In terms of flowability measurements, the carboxylic acid promoted notable increase in

additive.

similar effects compared to each other, but improving efficiency in comparison to no

similar to grinding without additive. For the calcium carbonate the additives presented

Alcohol and glycol were quite effective, while the use of carboxylic acid resulted in results

alumina, the grinding aids show different efficiency in reducing energy consumption:

and powder flowability measurements of the product were conducted. In the case of

After defining materials and establishing experimental methods, first batch grinding tests

or continuously operated ball mill as well as an reflector-wheel air classifier are selected.

acid and a Glycol. For the experiments, a 4 liter batch ball mill and a 47 liter, batch-wise

studied. Three substance classes were adopted as grinding aids: An Alcohol, a Carboxylic

In this project, dry grinding of the materials alpha alumina and calcium carbonate is

Amount of material coated on equipment surfaces.

Total mass of product inside the mill and residence time

Powder flowability;

Tendency of fine particle agglomeration;

Product fineness after grinding;

aids impact powder material mainly in:

consumption and/or to reach a certain product fineness. During milling operations, grinding

to the process in order to increase the product throughput, decrease the specific energy

by grinding aids. Grinding aids are defined here as liquid or dry substances that are added

manipulation of the material properties and, thus, the grinding and classification efficiency

optimizing and scaling industrial dry grinding processes, with a special focus on the

This project aims in developing a system engineering approach for understanding,