BLENDING & SEGREGATION FORUM BSF2019-EU...BLENDING & SEGREGATION FORUM BSF2019-EU The Scientific Conference portion of the Forum (Tuesday & Wednesday) features distinguished keynote

BLENDING & SEGREGATION FORUM

BSF2019-EU

09-12 December 2019

U Parkhotel

Enschede, NL

Organized and presented by:SciFora and MercuryLab

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Welcome to BSF2019-EUOn behalf of MercuryLab and SciFora, we welcome you to the Inaugural Blending & Segregation Forum (BSF2019-EU). We have assembled an outstanding group of speakers from Academia, Industry and the vendor community.

We want to acknowledge and thank our main sponsors, Rocky DEM for the Welcome Reception, Granutools for the Poster Reception, SciFora for the Poster Competition, Huxley Bertram for the Banquet, and Coupi for the catered lunches. All BSF sponsors and exhibitors are acknowledged on our website (blendingsegregation.com).

Attached you will find location details, agenda, speakers abstracts/ bios, and contact information.

To all attendees and speakers, thank you for your support and contribution to BSF2019-EU! We look forward to seeing you at the Forum.

A special thank you goes to the MercuryLab team for all their efforts in helping to organize this inaugural forum.

• Anthony Thornton-- Professor of Granular Materials, University of Twente and co-founder of MercuryLab

• Donna Fitzsimmons– Chief Financial & Operating Officer, MercuryLab

• Hao Shi—Head of Sales and Consultancy, MercuryLab and PostDoc at University of Twente

Best regards,

Thomas Weinhart, Chair of Scientific Committee-- Multiscale Mechanics, University of Twente;ChiefTechnical Officer, MercuryLab

Jean LeFloch-- SciFora Scientific Forums 2

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Directions to the U Parkhotel

The trains start directly from Amsterdam Airport (in the basement), there are signs with a picture of a train everywhere.

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BSF2019 – EU09-12 December 2019

Exhibitors and Sponsors:

• Vendor Tables: 10-11 December 2019

• During the Tuesday and Wednesday conference, vendor tables will be set up in room C1 at the back of the conference room. Please take the time to learn the technologies they have to offer and meet the teams. The vendors exhibiting include Huxley Bertram, Coupi, Delft Solids Solutions, MercuryLab, Natoli Scientific, Wolfson Centre for Bulk Solids Handling Technology, and SciFora.

• Vendors will be able to set up their tables in room C1 on Monday 09 December from 9:00 to 17:30 or Tuesday morning. (table dimensions are 140cm x 80cm)

• Special thanks to Rocky DEM for sponsoring Monday’s Welcome Reception and to Granutools for sponsoring Tuesday’s Poster Reception. Also special thanks to Huxley Bertram, Coupi, Natoli, The Wolfson Centre, Delft Solids Solutions and SciFora for their participation. Please note: All Forum attendees are invited to Monday’s Welcome Reception!

• Special thanks also goes to Odette Scheer and her team at the U Parkhotel for helping to organize and provide a beautiful venue for the Forum.

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When and where to meet, how to park?

Monday Workshop

(optional)

Registration 11:15 Lobby of U Parkhotel (group will walk together to Horst Tower)

Workshop begins 12:00 Lab location- Horst Tower HT1300 and Meander ME113A

Welcome Reception 18:30 U Parkhotel in the Meeting Lounge (sponsored by ROCKY DEM)

ALL FORUM ATTENDEES ARE INVITED

Tuesday Conference

Registration 8:00 U Parkhotel in the Meeting Lounge

Speakers begin 8:30 U Parkhotel Conference Room C2

Flash Presentations 15:30 U Parkhotel Conference Room C2

followed by poster presentations and reception in the Meeting Lounge

Forum Banquet 19:30 U Parkhotel restaurant

Wednesday Conference 8:00 U Parkhotel Conference Room C2

Thursday Symposium 8:45 U Parkhotel Board Room

(optional)

Parking information: Parking is free for guests at the U Parkhotel

Exhibitor Information:

Vendor Table Demo Set-Up: Monday 09 December, 13:00 to 17:30 Room C1

If you are lost or need information, please call or text:

Jean LeFloch: +1 847 275 4799

Key Events:

Monday, 09 December 2019: (Optional Workshop)

• 11:15 Forum and workshop registration

• U Parkhotel Meeting Lounge (Workshop attendees meet here to walk to Workshop on campus)

• 12:00 - 18:30 Short Presentations, Case Studies (divided into 2 groups), Partner presentations

• Lab location-in the lab Meander ME113A and Horst Tower HT1300

• Lunch and Breaks will be provided

• 18:30 Welcome Reception at U Parkhotel in the Meeting Lounge, sponsored by ROCKY DEM. All forum attendees are invited!

Tuesday, 10 December 2019:

• 8:00 Registration and Introduction (U Parkhotel Meeting Lounge)

• Attendees move to room C2 after registering for Conference

• 8:30 – 15:15pm Speaker Presentations

• All Speaker Presentations will be in room C2

• All Breaks and Vendor Display tables will be in room C1

• Lunch will be provided in the U Parkhotel Restaurant

• 15:30 Flash Presentations, followed by poster presentations and reception

• Meeting Lounge

• 19:30 Forum Banquet

• U Parkhotel restaurant

Wednesday, 11 December 2019:

• 8:00-17:30 Speaker Presentations

• Room C2 U Parkhotel

Thursday, 12 December 2019: (Optional Symposium)

• 8:45 Introduction

• U Parkhotel Boardroom

• Lunch will be provided in the Boardroom

• 9:00-11:00 Casual presentations/discussions focused on rotary tablet presses, including modeling & simulation of die compaction

• 11:00-15:00 Presentation & discussion of die compaction numerical models

• 15:00 End of Symposium and Forum

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BLENDING & SEGREGATION FORUM

BSF2019-EU

The Scientific Conference portion of the Forum (Tuesday & Wednesday) features distinguished keynote speakers who will anchor thetechnical sessions:

• Mike Bradley--Professor in Particle and Bulk Technology, Director of the Wolfson Centre for Bulk Solids Handling Technology, Head of the Greenwich Manufacturing Group at the University of Greenwich

• Jan Wieringa-- Lead Scientist, Unilever, NL

• Paul Mort-- Professor at Purdue University; 24 years of experience at P&G

• Anthony Thornton-- Professor of Granular Materials, University of Twente and co-founder of MercuryLab

• Nico Gray-- Professor of Applied Mathematics, University of Manchester

• Stefan Luding-- Professor of Multiscale Mechanics, Faculty of Engineering Technology, University of Twente

• Benjy Marks-- Lecturer, School of Civil Engineering, University of Sydney

Keynote Speakers

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Workshop (Monday, 09 December, optional event limited to a small group)

11:15 Workshop registration (U Parkhotel, De Veldmaat 8, 7522 NM Enschede)

11:40 Depart to meeting room 1300 at Horst Tower

12:00 Welcome and introduction

12:10 Short presentations

● Stefan Luding University of Twente (30 mins, 12:10 - 12:40): An introduction to calibration and validation: methods and challenges

● Jerome B. Johnson Coupi lnc (30 mins, 12:40 - 13:10): The importance of calibration, verification & validation in mechanistic modeling.

● Anthony Thornton MercuryLab B.V. (20 mins, 13:10 - 13:30): Bayesian calibration/validation & uncertainty propagation.

13:30 Lunch break

14:00 Focused topics (in 2 groups)

Topic 1: Blending & Segregation (14:00 - 15:15 including 15 mins of split groups)

● Anthony Thornton MercuryLab: Experimental calibration and validation of simulations on segregation and mixing.

● Hao Shi MercuryLab : Effect of particle size and cohesion on powder yielding & flow.

Lab tour 1: (14:00 - 15:15 including 15 mins of split groups)

Topic 2: Powder Compaction (15:15 - 16:30 including 15 mins of split groups)

● Martin Bennett Huxley Bertram: Experimental study on the powder compaction behaviour using limestone powders.

● Luca Orefice RCPE: Deformable and breakable particle clusters for modelling plastic and brittle materials. Part 1: model and calibration.

Lab tour 2: (15:15 - 16:30 including 15 mins of split groups)

16:30 Coffee break

16:45 Partner presentations

● Filip Francqui Granutools (15 mins + 5 mins Q&A, 16:45 - 17:05): Cohesion measurement for non-consolidated granular materials: principle

and applications.

● Michael Bradley The Wolfson Centre for Bulk Solids Handling Technology (15 mins + 5 mins Q&A, 17:05 - 17:25): Know your Enemy.

● Johan Groen Delft Solids Solutions (15 mins + 5 mins Q&A, 17:25 -17:45) The Importance of Solid(s) Characterization.

17:45 Discussion, recommendations and conclusions

18:15 End of workshop; proceed to Welcome Reception at U Parkhotel Welcome Reception is being sponsored by Rocky DEM

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Tuesday 10 December: Scientific Conference, day 1 01dec19

8:00 Registration & Introduction Session 1: overview of mixing/demixing (solid-solid systems)

8:30 Stefan Luding University of Twente Review on segregation in flowing and vibrated granular systems

9:15 Jan Wieringa Unilever An industrial view on blending and segregation of consumer goods

10:00 morning break (15 minutes)

10:15 Mike Bradley The Wolfson Centre An industrial overview of causes, effects, consequences, solutions

for bulk solids handling technology and the current state of art in material characterisation and problem prediction

11:00 Barbara Schönfeld AbbVie Germany In-line blend uniformity monitoring using near-infrared spectroscopy as PAT tool

11:30 Wouter K. den Otter University of Twente Segregation of granular particles by mass, radius and density in a horizontal rotating drum

12:00 Bastiaan HJ Dickhoff DFE pharma How to approach mixing for challenging low dose pharmaceutical formulations

and how can continuous mixing play a role?

12:30 Lunch break (60 minutes) Session 2: current research

13:30 Benjy Marks University of Sydney segregation, mixing and breakage during granular flow

14:15 Susantha Dissanayake The Wolfson Centre Cellular automata modelling for simulating segregation of wood pellets

for bulk solids handling technology in silo filling and discharge

14:45 Kasper van der Vaart University of Twente Granular buoyancy in the context of segregation of single large grains in

dense granular flows

15:15 afternoon break (15 minutes)

15:30 Theresa Hoermann RCPE, Graz Production of tablets at RCPE’s continuous wet granulation tableting line

16:00 flash presentations, followed by posters presentation and reception, sponsored by GRANUTOOLS

19:30 Forum dinner

notes: 1-keynote presentations are highlighted in blue

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Wednesday, 11 December: Scientific Conference, day 2

8:00 Introduction Session 3: Modelling & Simulation

8:15 Nico Gray University of Manchester Particle segregation in dense granular flows

9:00 Anthony Thornton U. of Twente; MercuryLab Multiscale modelling of industrial granular materials

9:45 morning break (30 minutes)

10:15 Anton Kulchitsky Coupi, Inc. IBC blending performance analysis depending on particle dimension & shape

10:45 Thomas Weinhart Twente/MercuryLab B.V. Coarse-graining with MercuryCG - from discrete particles to continuum fields

11:15 Marina Sousani DEM Solutions Ltd Understanding the mechanistic behaviour of powder mixing with the use of DEM

modelling & simulation

11:45 Clovis Maliska, Jr. ESSS Ltd, Brazil Next-generation DEM technology using Rocky: some examples and case studies

of blending, mixing and segregation in practical applications

12:15 Lunch break (75 minutes) Session 4: experimental aspects, case studies & applications

13:30 Paul Mort Purdue University (ex P&G) Powder flow and cohesion - balancing industrial and academic perspectives

of product design and processing

14:15 Patrick Verolme Delft Solids Solutions Determining the amount of segregation using analytical measurement methods

14:45 Mike Bradley The Wolfson Centre Influences of flowability and permeability on air elutriation segregation

for bulk solids handling technology of pharmaceutical powders

15:15 afternoon break (15 minutes)

15:30 Naveen Mani Tripathi Granutools Physical characterization of powder blends with a focus on electrostatic properties

16:00 Olukayode Imole Hosokawa Micron B.V. Effect of process variables and material flow on filling consistency and final

performance of lactose-based dry powder inhaler formulations

16:30 discussion & conclusion

17:30 End of the BSF2019-EU Scientific Conference

Symposium (Thursday, 12 December, optional event limited to a small group)

This 6-hour intense symposium is limited to a small group and gathers presses/compaction experts who attended the Conference and

are willing to update the group on their recent findings and research. Critical topics such as punch sticking, compaction models,

feeders and PAT aspects will be explored.

8:45 introduction: scientific aspects of rotary tablet presses: design/operation, PAT and die compaction

9:00 casual presentations/discussions focused on rotary tablet presses, including modeling and simulation of die

compaction (limited to a small group)

● Anton Kulchitsky & Jerome B. Johnson Coupi, Inc

● Anthony Thornton & Thomas Weinhart University of Twente; MercuryLab

● Theresa Hoermann & Luca Orefice RCPE, Graz

● Paul Mort Purdue University, previously P&G

● Martin Bennett Huxley Bertram

● Robert Sedlock Natoli

11:00 presentation and discussion of die compaction numerical models:

● the modelling challenges of die compaction

● MercuryLab B.V.

● University of Twente

● Coupi Inc.

● RCPE, Graz

13:30 short presentations (continued)

the following topics will be presented during the morning & afternoon discussions:

● the discrete nature of punch sticking and how to characterise it

● the effects of production press stiffness on tablet compaction strain rate

● simulation of load-limiting presses using a compaction simulator

● powder handling/feeding and mechanical aspects of rotary tablet presses

● suitability of existing rotary press feeders for continuous tableting

15:00 conclusion of the Symposium and end of Forum

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Sponsors & Exhibitors

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Presentation Bios & Abstracts for the Conference

Day One-Morning Session-U Parkhotel Room C2

Stefan Luding- Keynote Speaker

University of Twente, the Netherlands

Stefan Luding studied physics at Bayreuth, Germany (reactions on complex and fractal geometries). He did his PhD on the simulations of dry granular materials in the group of Prof. A. Blumen in Freiburg, Germany and spent his post-doctorate time in Paris IV, Jussieu, with E. Clement and J. Duran, before he joined the Computational Physics group in Stuttgart, Germany, with Prof. Herrmann in 1995, where he achieved his habilitation in 1998.

In 2001, he moved to DelftChemTech at the TU Delft, Netherlands, as Assoc. Prof. Particle Technology. Since 2007 he chairs the group Multiscale Mechanics (MSM) at the Faculty of Engineering Technology and MESA+ at the University of Twente, Netherlands.

His major research expertise is on granular matter, non-Newtonian flow rheology, non-linear solids, particle interactions, cohesive powders, asphalt, composites, bio-/micro-fluid systems, self-healing materials and most of all on micro-macro transition methods.

Among many other tasks and services for the community, he is since 1998 Managing Editor in Chief of the journal Granular Matter as well as, since 2005, president of AEMMG organizing the Powders and Grains conference series with the next event taking place in Buenos Aires, Argentina, July, 2021.

(See next page for Abstract)

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Stefan Luding- Keynote Speaker

University of Twente, the Netherlands

(Continued)

Review on segregation in flowing and vibrated granular systems

• For this session, a review over some research on segregation in the past 20 years, including segregation in chute flows or vibrated granular systems will be given, with focus on some of the traditional, long-standing questions:• - what are the different mechanisms causing segregation? [1,2] • - what causes hydrodynamic/convective flows that can influence segregation? [7,8].• - what segregation mechanisms are specific to vibrated granular media? [2,5], and• what are the important/dominating control parameters [7,8] of vibrated granular systems?• - is it possible to describe discrete granular particle systems, including segregation by continuum methods?• Phenomena like convection [2,8], particle-size driven geometric segregation [1], thermal fluctuations [3], shear- or temperature-gradients [4], condensation [5], or detachment [7], • will be discussed and an outlook for a hydrodynamic description of vibrated systems [8] will be given. The review will end with a brief overview of the session.• REFERENCES

• [1] Journal de Physique I 5.12 (1995): 1527-1537.• [2] Pharmaceutical technology 20.8 (1996): 42-44; Phys. Rev. E, 50:R1762 (1994); Phys. Rev. Lett. 69, 1367 (1992)• [3] Proceedings IUTAM Symposium on Segregation in Granular Flows, pg 305-310 (2000); Phys. Rev. E 58, 813-822 (1998)• [4] Proceedings IUTAM Symposium on Segregation in Granular Flows, pg 297-303 (2000);• [5] Phys. Rev. Lett., 86, 3423-3426 (2001)• [6] Int. J. Mod. Phys. C 23(8), 1240014 (2012) • [7] Phys. Rev. E, 50:4113 (1994) [8] Granular Matter 15(6), 893-911 (2013) 15



Jan Wieringa-Keynote Speaker

Unilever, NL

Jan Wieringa received an MSc and PhD in physics from Delft University of Technology (Netherlands). He spent most of his working life in Unilever R&D, for several categories including foods and laundry products. A common theme in his work is the relation between the product and process. This came back in work in areas like emulsification and crystallization but also powder flows

An industrial view on blending and segregation of consumer goods

On any given day, 2.5 billion people use Unilever products to feel good, look good and get more out of life. We sell consumer products in the three divisions Foods and Refreshment, Home Care and Beauty & Personal Care. Products in the form of powder are mainly found in savoury products (soups, sauces, etc.), beverages (tea) and laundry detergents.

For these product categories, mixing and dosing are key operations. The product formulations can be very complex, including ingredients with very different properties (density, size, shape, mechanical properties) and amounts. Implementations need to balance consumer demands in terms of product quality and performance with process efficiency. This requires well-designed factory operations, which are able to deal with the portfolio complexities, and appropriate analysis tools and methodologies. Good scaling between lab and factory is an important element of that.

In the presentation, some typical challenges will be discussed.

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Mike Bradley- Keynote Speaker

The Wolfson Centre for Bulk Solids Technology

Mike Bradley is Professor in Particle and Bulk Technology,Director of the Wolfson Centre for Bulk Solids HandlingTechnology and Head of the Greenwich Manufacturing Group atthe University of Greenwich. He was awarded both his honoursdegree and PhD from Thames Polytechnic (now the University ofGreenwich) and, as manager/director, provides technicalleadership in all aspects of bulk solids handling. His particular areasof interest lie in pneumatic conveying, design of hoppers and silos,dust control, plant integration and maintenance of product quality.He is Chair of Solids Handling and Processing Association (SHAPA),and a member of Materials Handling Engineers Association(MHEA) and of the Institution of Mechanical Engineers BulkMaterials Handling Committee (IMechE). He was awarded aprofessorship in 2006 and the directorship in 2008.

(See next page for abstract)17



Mike Bradley- Keynote Speaker

The Wolfson Centre for Bulk Solids Technology

(Continued)

Segregation in Powders and Bulk Solids:An Industrial Overview of Causes, Effects, Consequences, Solutions and the Current State of Art in Material Characterisation and Problem Prediction

Synopsis

The Wolfson Centre team have spent the last 45 years solving and preventing bulk solids handling problems in industrial processing systems, yet segregation still remains one of the most common difficulties brought to us. Many companies suffer large losses in product quality, customer confidence and profitability due to the problem.

• This presentation takes an industrial perspective on the practical experience and state of the art in:

• The causes and effects of segregation in industrial processes

• The kinds of processes and materials that are most at risk

• Current means to identify formulations, products and processes that are at risk

• Means for predicting and mitigating segregation at formulation and process planning stages

• Experience with the usefulness of different modelling techniques

• The many different solutions that can be applied to prevent or eliminate the problem

• Where research is needed to augment our available solutions

• One of the main questions we will seek to explore is this; when this phenomenon has been so commonplace in manufacturing over so many decades, and so many different solutions are available and proven to be effective, why is it that so many equipment and product designers and process users are still being caught out by the problem? And what should we be doing in the community of particle technology, to prevent these avoidable losses in the wider world?

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Barbara Schönfeld

AbbVie, Germany

Barbara Schönfeld joined the NCE (new chemical entity) Formulation Sciences department at AbbVie Ludwigshafen (Germany) as a Formulation Scientist in 2015.

Within this position, she works on several early-phase development programs and she successfully implemented PAT for the blending process.

In addition to her position at AbbVie, she is a PhD student in a collaboration with the Pharmaceutical Technology Institute of the Rheinische-Friedrich-Wilhelms-University Bonn (Germany) focusing on the evaluation of a new technology to manufacture ASD (amorphous solid dispersion) formulations.

Barbara holds a degree in Pharmacy from the Ruprecht-Karls-University of Heidelberg (Germany) and is an expert pharmacist in the field of pharmaceutical technology.

In-line Blend Uniformity Monitoring Using Near-Infrared Spectroscopy as Process Analytical Technology (PAT) Tool

In the manufacture of solid dosage forms, the “uniformity of single-dose dosage forms” (Ph. Eur. 2.9.40) is a critical quality attribute in order to ensure the correct dosage of divided dosage forms such as tablets. In many cases, an important process to be evaluated in the development of the final dosage form directly linked to the aforementioned quality attribute is the blending process of powder blends – especially when the blending process represents the last process step before tableting.The determination of the blend uniformity of a powder blend should therefore ideally be used to determine the homogeneity of the blend and thus lay the foundation for the dosing uniformity of the final dosage form. Conventionally the blend homogeneity is tested using the sample thieving method. Here a number of samples from the blend are obtained at certain positions in the blending container and tested for homogeneous active pharmaceutical ingredient content by HPLC. As this approach relies on off-line analytics, the results are generated with time delay with respect to the production step.A more elegant approach is the in-line monitoring of blend uniformity with NIR. We here present our at AbbVie adapted approach of in-line blend uniformity using the SentroPAT NIR sensor (Sentronic). The blending endpoint is determined by an F-test using moving block standard deviation. The implementation of online data evaluation lead to a better understanding of the overall blending process, e.g. reduction of blending time or reduction of process steps..

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Wouter K. den Otter

University of Twente, NL

Wouter den Otter studied applied physics at the Eindhoven University of Technology (TUE), followed by a PhD in chemical physics at the University of Twente (UT) in Enschede. After a postdoc at the chemistry department of the University of Manchester Institute of Science and Technology (UMIST), he returned to Twente as postdoc and assistant professor in the computational biophysics group, and currently he is associate professor in the multiscale mechanics group. His research focuses on statistical mechanical simulations, studying various systems ranging from colloids, rods and polymers to proteins and granular matter, both in and out of equilibrium.

Segregation of granular particles by mass, radius, and density in a horizontal rotating drum

The impact of particle properties on segregation and mixing of bidisperse granular

beds in a rotating horizontal drum have been studied by discrete element method

(DEM) simulations. Bidispersities in radius, density, and mass have pronounced

influences on the stationary mixing pattern, although they hardly affect the

granules’ flow regime. At 50% fill level, all beds mix well for a Froude number of

approximately 0.56, corresponding to a flow regime intermediate to cascading and

cataracting, while segregation occurs both at lower (rolling and cascading regime)

and higher (cataracting/centrifuging regime) Froude numbers. These observations

are explained qualitatively by noticing that the angular drum velocity dictates the

flow regime, which in turn determines the effectiveness and direction of four

competing (de)mixing mechanisms: random collisions, buoyancy, percolation, and

inertia.20



Bastiaan HJ Dickhoff

DFE pharma

Dr Bastiaan Dickhoff joined the T&I department team at DFE Pharma in 2014 in the capacity

of Application Specialist OSD. Bastiaan has been working on assisting in application

development of excipients in area of Oral Solid Dose Forms based upon fundamental

knowledge of DFE Pharma’s excipients and advances in powder technology. His expertise lies

in the understanding powder behavior in batch and continuous processes coupled with

multivariat analysis. In addition, he is from a Technology and Innovation point of view

responsible for the outcome of external collaborations. Prior to working at DFE Pharma

Bastiaan held two (2) roles concerning the effect of powders in food and pharma at RSSL

(which is part for Mondelez International (UK)) and prior to that Bastiaan has worked between

2005-2012 for GlaxoSmithKline (UK) in various roles.

Bastiaan holds a PhD from the department Pharmaceutical Technology and Biopharmacy at

Groningen University, The Netherlands where he specialized in the relationship between the

role of lactose (excipient) and API for inhalation purposes.

(see next page for abstract)

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Bastiaan HJ Dickhoff

DFE pharma

(Continued)

How to approach mixing for challenging low dose Pharmaceutical formulations and how can continuous mixing play a role.

In the Pharmaceutical Industry powder mixing, being dry (or wet) mixing excipients with active pharmaceutical ingredients (API), is

key to ensure the safety (right drug dose) in a tablet or dry powder inhaler. Two industry developments further increase the need for

solid mixing techniques. First, the increasing potency of new API’s results in lower and lower dosed formulations to be developed,

and second the Pharma 4.0 initiative is driving companies to move from batch to continuous processing (incl. mixing).

In the industry mixing occurs in small scale batch processes up to around 50 kg for dry powder inhalers and up to around 1000 kg in

formulations for tablets. Typically two approaches of mixing occur, being: 1) random mixtures where API and Excipients are

matched to reduce the chance of segregation during and after blending on stability and further processing; and, 2) adhesive or

ordered mixtures in which the API is milled or micronized to sub 10-50 micron particles and which are combined with large, dense

good flowing excipients. In the latter approach, the binding force is cohesion and in particular the Van der Waals forces, which avoid

the segregation potential of a mixture.

In this study we focus on the mixing challenges related to the two mentioned developments in the pharmaceutical industry: (a) very

low dose API mixing for direct compression and the effect of excipient morphology on the content uniformity and powder behavior

and (b) moving from batch to continuous processing (mixing) . In both studies, both adhesive and ordered mixtures have been made

by using simple mixing procedures.

To understand the role of excipient morphology on very low dose direct compression (DC) formulations we investigated

formulations having a dose between 0.5 and 0.005%w/w API. These formulations were made with a range of (large) lactose-based

excipients with different surface morphologies. The API size was calculated as per Rohr et al., 2006, to have enough particles

present to enable a good content uniformity. Samples were taken both after the mixing process of the powder blend, as well as

after tableting. This enabled us to analyze content uniformity of the blend versus content uniformity in the tablet. In addition, it

enabled us to assess the level of segregation during holding time and potential segregation during the tableting process (RoTab).

To understand the differences in content uniformity (and behavior) batch mixing (Turbula mixer) was compared with continuous

mixing (Gericke continuous mixer) with a fixed API dose. Samples of the powder blend were taken at different mixing time points

and were analyzed. In addition, tablets were made from both blends to investigate the impact of both mixing processes on the

tableting process and the resulting tablets. Clear differences in content uniformity and powder behavior were observed between

both processes.

In both case studies it was concluded that in order to obtain non-segregated homogeneous powder blends and end products, the

correct excipient (morphology) should be selected for the API size and the mixing process of choice.. These conclusions are

applicable to powder mixing for oral solid dose applications (e.g. tablets) as well as dry powder inhalers.

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Day One-Afternoon Session-U Parkhotel Room C2

Benjy Marks- Keynote Speaker

University of Sydney

Dr Marks is a Lecturer in the School of Civil Engineering at The University of Sydney. His research is based in the mechanics of granular media, in particular the processes of segregation, mixing and grain crushing. He is involved in developing new X-ray based techniques for investigating the interior of these materials in a dynamic environment, giving us the ability to measure the evolving velocity and grain size distribution fields over time. These new measurements are the key to enable us to create and validate new mathematical and computational tools for understanding this complex behaviour.

Segregation, mixing and breakage during granular flow

There is a complex interaction between the dynamics of a flowing material and its grain size. The

grain size distribution can change in space for many reasons, all of which are poorly

understood. Here, I will present recent experimental advances which allow us to probe inside

flowing material and observe these phenomena. The insights we have gained from these

observations are allowing us to describe quantitatively the evolution of the grain size distribution to

a plethora of competing mechanisms, such as segregation, mixing and breakage. I will show how

simple numerical models can capture this behaviour and describe how these can be easily extended

to complete mechanical models which couple realistic flow rheology with grainsize dynamics.

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Susantha Dissanayake

Wolfson Centre for Bulk Solids Technology

(Jeff) Susantha Dissanayake Reading for PhD, AFHEA

Susantha Dissanayake is a PhD research student working at the Wolfson Center for Bulk Solid Handling

Technology, University of Greenwich, United Kingdom. He is studying segregation of wood pellets during silo

filling and discharge using a Cellular Automata (CA) modelling approach. CA modelling is a discrete modelling

approach which consists of simple set of rules: which were developed by close observation of free surface

segregation occurring during particle heap formation. In his study, the suitability of CA modelling for bulk

material handling is tested and a control methodology is to be developed to assist with blending pellets to

control fines level in actual handling systems at a leading power generation plant in the UK. Susantha finished

his bachelor’s special degree in Science and Technology and finished his master’s degree in sustainable process

development from University of Moratuwa Sri Lanka. He worked in academia for three years before he joined

the University College of Southeastern Norway (UCSN) for his second master’s degree in process technology.

After completion of his master’s degree he again joined academia and continued his teaching and research

career in Norway. He started his doctoral studies at University of Greenwich UK in December 2017. Currently,

he is in his second year of the study. During his research career he has worked in modelling and simulation field

and has published more than 10 research papers. His teaching qualifications were recognized by UK

Professional Standard Framework (UKPSF) and awarded Associate Fellow of the Higher Education Academy

(AFHEA) in July 2019. EDUCATION & CREDENTIALS BSc (special)., University of Sri Jayewardenepura, Sri

Lanka, 2009 MSc., (Sustainable Process Development) University of Moratuwa, Sri Lanka, 2011 MSc., (Process

Technology), University Collage of Southeast Norway, 2016 PhD., (Reading) University of Greenwich.




Susantha Dissanayake

Wolfson Centre for Bulk Solids Technology

(Continued)Cellular Automata Modelling for Simulating Segregation of Wood Pellets in Silo Filling and Discharge

Wood pellets are widely used in power generation, often co-fired in traditional coal fired power stations. Wood

pellets are a low carbon energy resource which can naturally be replenished. Wood pellets are handled often by

conventional coal handling equipment such as conveyer belts, pneumatic conveyors, and frequently stored in

large silos and domes. During handling and storing, wood pellets degrade into fines and dust. Wood pellets

mixed with fines and dust have a tendency to segregate in handling, especially silo filling and discharge. This

causes spikes in fines and dust level which result in suboptimal pneumatic conveying (high energy

consumption). Due to variable operational conditions, dust tend escape from processes can be more

problematic, leading to dust accumulation in the environment, requiring more intense cleaning. Moreover, it

leads to increased risk of fire and explosion. Unsteady unit operations including particle milling may consume

excess amount of energy, resulting in additional cost in parasitic load.

In this study, segregation during silo filling and discharge is modelled using Cellular Automata (CA) approach.

CA modelling is a mechanistic, deterministic approach, in this case using a simple set of rules derived based on

close observation of particle heap formation and free surface segregation. The aim of this study is to test the

suitability of CA modelling for estimating segregation in bulk material handling. 2-D simulations have been

developed using Excel VBA and tested against laboratory scale test rigs. These CA models have shown an

excellent capability to predict segregation in silo filling and discharge. All key features of behaviour seen in the

experiments are captured in the model; in filling, due to free surface segregation, higher level of fines was

predicted under the feeding point (usually the centre of the silo), and in discharge the tendency for fines to sift

downwards through the moving layer is also captured. This paper discusses the modelling technique, the

logical rules required to achieve the desired behaviour and the validation against experimental observations.

25



Kasper van der Vaart

University of Twente

Kasper van der Vaart obtained a bachelor in physics in Amsterdam and a masters in Nanomaterials in Utrecht. He

did his promotion at the EPFL on the topic of granular materials, after which he went to Stanford for a postdoc

on the topic of collective swarming behaviour. Now he is back in the Netherlands as a postdoc in the Multi-scale

mechanics group at the University of Twente.

Granular buoyancy in the context of segregation of single large grains in dense granular flows

Modelling of particle-size segregation in dense granular flows could benefit from a better understanding of the segregation behaviour of an isolated large particle in a flow of smaller grains. In one previous study, the force along the direction of segregation experienced by such an intruder particle was measured and decomposed into a modified Archimedean buoyancy force and a segregation lift force. Here we present a micro-mechanical analysis of this new granular buoyancy force in order to connect the micro-scale contact behaviour to the macroscopic force. In doing so we uncover evidence that links the magnitude difference between buoyancy and gravity acting on large intruders toa decrease in surface contact density. Our findings reveal micro-scale insights into buoyancy in dense granular flows; support the use of the Voronoiapproximation for calculation of the buoyancy force; and substantiate a specific force decomposition into buoyancy and segregation lift forces. Ultimately, these insights are expected to impact development of models for size segregation by linking micro and macro behavior.

This work studies the forces on a single large grain in a mixture of smaller grains, such bidisperse granular mixtures with a low large particle concentration are abundant in industry. 26



Theresa Hörmann

RCPE, Graz

Theresa obtained her doctoral degree in chemical engineering at the Institute of Process and Particle Engineering of the Graz University of Technology, Austria, in 2019.

During her doctoral studies she worked on the development of a continuous process line to produce tablets via hot-melt extrusion and pelletisation, following the principles of Quality by Design. Her PhD project was one of three use case streams in the European Consortium on Continuous Pharmaceutical Manufacturing (ECCPM). In addition, Theresa taught courses on particle technology and pharmaceutical engineering at TU Graz.

Production of Tablets at RCPE’s Continuous Wet Granulation Tableting Line

With the shift towards continuous manufacturing in the pharmaceutical production of oral solid dosage forms (ODFs), especially direct compression (DC) and continuous wet granulation (WG) have major interest in research and industry. Wet granulation is typically applied, when direct compression is not feasible due to poor compressibility or segregation issues in the given formulation.

As one of the first equipment providers, GEA has developed a turn-key continuous wet granulation and tableting line, i.e., the ConsiGmaTM 25 continuous tableting line (CTL). The line is composed of the following, fully interlinked units: i) a continuous feeding and twin-screw wet granulation (TSWG), ii) a six-segmented continuously-operated fluid bed dryer (FBD), iii) a granule conditioning unit (GCU) with a conical mill, a scale and a mini-batch ribbon blender, and finally, iv) a tablet press. The continuous operation of the whole process line is achieved by the connection of sub-units via pneumatic transfer lines. Thus, the process conditions for intermediate products and blends are significantly different from batch manufacturing.

In our use-case study, a finely milled and an unmilled tracer material was added to the granules as an external excipient in the line’s mini-batch ribbon blender. After adding the lubricant, the produced compression mix was transferred to the tablet press and compressed to tablets. The final tablet’s tracer content was evaluated and compared for both tracers to assess the effect of particle size on content uniformity. Surprisingly, tablets were less uniform for the milled tracer material, contradicting findings from offline sifting segregation tests. A thorough root-cause analysis for these observations will be presented, considering the process conditions in feeding, blending, the pneumatic transfer line and in the tablet press. Based on different segregation mechanism models, hypotheses are developed and challenges and benefits in continuous pharmaceutical manufacturing lines demonstrated.

27


Day Two -Morning Session-U Parkhotel Room C2

Nico Gray—Keynote Speaker

University of Manchester

Nico Gray is Professor of Applied Mathematics at The University of Manchester and is an expert on granular avalanches and the particle segregation that occurs within them. He holds a BSc in Mathematics from Manchester, a PhD on “sea ice dynamics” from the University of Cambridge and a Habilitation in “continuum mechanics and geophysical dynamics” from the Technical University of Darmstadt. A key feature of Nico’s research is that he performs small scale experiments that provide a strong motivation for his theoretical and computational work. Over recent years he has also collaborated extensively with geologists working on hazardous geophysical flows, such as debris-flows, rockfalls and pyroclastic flows. This has included field work, as well as novel large-scale experiments at the United States Geological Survey (USGS) debris-flow flume in Oregon. Nico holds a prestigious Royal Society Wolfson Research Merit Award as well as EPSRC Established Career Fellowship. Both these awards are focussed at applying the significant theoretical breakthroughs that he has made in understanding the rheology of granular flows and how they segregate to important industrial unit operations, such as chute flows, silos, conveyor belts and rotating drums.


http://www.maths.manchester.ac.uk/~ngray/

http://www.manchester.ac.uk/

http://dx.doi.org/doi:10.1029/2011JF002185

http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/M022447/1

http://www.annualreviews.org/doi/abs/10.1146/annurev-fluid-122316-045201



Nico Gray—Keynote Speaker

University of Manchester

(Continued)

Granular materials composed of particles with differing grain sizes,

densities, shapes, or surface properties may experience unexpected

segregation during flow.

This review focuses on kinetic sieving and squeeze expulsion, whose

combined effect produces the dominant gravity-driven segregation

mechanism in dense sheared flows. Shallow granular avalanches that

form at the surface of more complex industrial flows such as heaps, silos,

and rotating drums provide ideal conditions for particles to separate, with

large particles rising to the surface and small particles percolating down

to the base. When this is combined with erosion and deposition, amazing

patterns can form in the underlying substrate. Gravity-driven segregation

and velocity shear induce differential lateral transport, which may be

thought of as a secondary segregation mechanism. This allows larger

particles to accumulate at flow fronts, and if they are more frictional than

the fine grains, they can feedback on the bulk flow, causing flow fingering,

levee formation, and longer runout of geophysical mass flows.29

Presentation Bio & Abstract for the Conference


Anthony Thornton—Keynote Speaker

University of Twente; MercuryLab

He co-founded the open-source simulation code, MercuryDPM and has been involved in many successful grant applications including a prestigious personal Vidi project on ‘Advanced Modelling of Segregation and its Application to Industrial Processes’, worth over a million euros. He works at the interface of disciplines, as highlighted by the diverse journals he publishes in (e.g. Journal of Fluid Mechanics, Computational Particle Methods, Granular Matter and Physics Review Letters). His research has applications in many areas including pharmaceutical, food science, mining, particle technology and geophysics.

In 2015 he co-founded the UT spin-off company MercuryLab, whose aim is to make MercuryDPM accessible for industry utilisation. Via this he has been involved in various industrial projects looking at many aspects of granular flows. In 2017 he gained the title Professor of ‘Granular Materials’, a new chair within the Multiscale Mechanics group, Department of Fluid and Thermal Engineering, at the University of Twente, The Netherlands.

(see next page for abstract) 30

Presentation Bio & Abstract for the Conference


Anthony Thornton—Keynote Speaker

University of Twente; MercuryLab

(Continued)

Multiscale modelling of (industrial) granular materials

Creating accurate predictive computer simulations, virtual prototypes, of complex granular industrial processes has many challenges. In this presentation I will review, with examples from both industry and the natural environment, recent advances in creating such virtual prototypes. The examples will focus on one of the key problems facing many industries, that of granular segregation/mixing, and will be demonstrated using our powerful open-source software suite MercuryDPM.

Firstly, I will briefly consider the problem of how to create a computer representation of an actual granular material, the so-called model calibration. I will show an example of how we use machine learning to go from a set of characterisation data to a calibration particle model.

Secondly, I will introduce the open-source code, MercuryDPM, and discuss how we can deal with large industrially relevant simulations. This includes:

1. The hierarchical-grid: This neighbourhood search algorithm efficiently computes contacts, even for highly poly-dispersed particle size-distributions.

2. Curved walls: Allowing the quick and exact computation of contact detection with complex industrially relevant geometries.

3. Upscaling: The use of effectively larger particles that have the same properties of the true-sized particles.

Finally, I will briefly introduce MercuryCG. An advanced coarse-graining statistical package to extract continuum fields such as density, velocity, structure and stress tensors I will show how the method can be used to:

1. Generate continuum fields such as density, momentum, stress, etc, from the discrete data, i.e. from the positions, velocity, orientations and/or forces of individual elements. Allowing an in-depth analysis of flows.

2. Extract a cheaper, problem-specific continuum model. Allowing cheaper/faster computations that are possible with particle simulations.

3. Allow more accurate integration with fluid solvers or other continuum models.31



Anton Kulchitsky

Coupi, Inc.

Dr. Anton Kulchitsky has degrees in Applied Mathematics (Masters) and Mechanics (Ph.D.) from

Moscow State University. He has over 20 years of applied research experience, including 10 years in

discrete element method development. He co-developed, with Jerome B. Johnson, the Polyphysica

particle dynamics model. Dr. Kulchitsky has led research projects related to sea-ice drift modeling,

NASA's asteroid retrieval mission, and water migration in lunar regolith. He is a Co-I on the CAESAR

comet sample return mission proposal, which seeks to return a volatile gas rich sample from comet

67P. He has also contributed to developing analytical and numerical methods to solve different

practical problems, including intensive droplet evaporation, ionospheric advection, and ultra-low

frequency electromagnetic wave propagation through the Earth's crust. Currently Anton Kulchitsky

is CTO of Coupi, Inc., where he leads the software development team. He is also a research

associate professor at the University of Alaska Fairbanks.

IBC blending performance analysis depending on particles dimensions and shape

Intermediate bulk container (IBC) blenders are widely used in the creation of homogeneous powder

mixtures as an important part of industrial processes in pharmaceutical, food, and chemical

industries. Particle size plays a significant role in blending properties, which makes a discrete

element method (DEM) analysis more challenging as it seldom can operate with actual particle

sizes and shapes due to the computational complexity of the method.

We utilize a scaling DEM analysis to study how particle size and shape influence mixing rates and

segregation and to predict the blending quality and performance in different areas inside a

standard IBC blender. We determine segregation rates during both blending and discharge as the

discharge is an important part of mixture production. As a result of the analysis, we propose a

standard procedure and create a modeling software application suitable to perform a qualitative

and quantitative performance prediction of full-scale IBC blenders.32



Thomas Weinhart


Thomas Weinhart studied Mathematics at the TU München, Germany (BSc) and Virginia Tech, USA (MSc, PhD). He is now Associate Professor in Thermal and Fluid Engineering at the University of Twente. He studies granular processes on all scales: he developed and experimentally validated contact laws for wetting, friction, cohesion and sintering; established coarse-graining as micro-macro method for extracting local macroscopic quantities from discrete particle data; modelled granular systems on the macroscale; and used FEM simulations to predicting the flow behaviour of large-scale systems. He now develops coupled methods for solving multi-scale, multi-physics problems, such as liquid migration, segregation of cohesive powders, sintering, 3D printing, tabletting, and wet granulation. In 2009, he co-founded MercuryDPM, a cutting-edge open-source software for particle simulations; and now leads the code development team. The code has several unique features that make it particularly apt to simulate complex industrial systems. All his research codes are publicly available in the software. For commercial use of the software, he co-founded MercuryLab, a spin-off company providing custom software, training and advice to companies on the design of process equipment.




Thomas Weinhart


(Continued)

Coarse-graining with MercuryCG – From Discrete Particles to Continuum Fields

Micro-macro transition methods are used to calibrate and validate continuum models from discrete data, obtained from experiments or simulations. Such methods generate continuum fields such as density, momentum, stress, etc., from discrete data, . i.e. positions, velocity, orientations and forces of individual elements. Performing this micro-macro transition step is especially challenging for heterogeneous and dynamic situations. Here, we present a promising technique, called coarse-graining, to perform this transition. This novel method has several advantages: by construction the obtained macroscopic fields are consistent with the continuum equations of mass, momentum and energy balance. Additionally, boundary interaction forces can be taken into account in a self-consistent way and thus allow for the construction of locally accurate stress fields even within one element radius of the boundaries. Similarly, stress and drag forces can be determined for individual constituents, which is critical for e.g. mixture and segregation models. Moreover, the method does not require ensemble-averaging and thus can be efficiently exploited to investigate static, steady and dynamic flows. The resulting fields may serve various purposes: an in-depth analysis of the material behavior; extracting a problem-specific continuum model; or even coupling of particle simulations with fluid solvers or other continuum models.

We show how to practically use coarse-graining for both steady and dynamic flows and mixtures, using our open-source coarse-graining tool MercuryCG. The tool is available as part of an efficient discrete particle solver MercuryDPM.

34



Marina Sousani

DEM Solutions, LTD.

Dr Marina Sousani holds a BSc degree in Civil Engineering from the University of Patras; Greece, an MEng degree in Civil & Structural Engineering from the University of Newcastle, and a PhD in Discrete Element Modelling (DEM) from Leeds University. Marina is a senior R&D engineer and has over 6 years’ experience modelling granular material using DEM and using experimental methods. She joined DEM Solutions Ltd in 2016 and her role involves the modelling of complex applications using EDEM. She also manages a number of research projects in collaboration with leading Institutes in order to implement the latest scientific advances in the EDEM software

(See next page for abstract)

35



Marina Sousani

DEM Solutions, LTD.

(Continued)

Understanding the mechanistic behaviour of powder mixing with the use of DEM

The mixing of bulk solids is a fundamental unit operation in a wide range of manufacturing industries. Performing this operation effectively is essential to the quality of the final product but the mechanics of mixing in common mixing units such as paddle mixers is still not fully understood, resulting in poor product quality and economic losses to manufacturers. In this context fine granular materials such as powders are particularly challenging because their fine particle size distribution gives rise to a complex elasto-plastic-adhesive behaviour that produces unwanted segregation and agglomeration in mixing processes. Understanding the mechanics of mixing of such solids is experimentally challenging due to the opaque nature of the system making numerical methods such as Discrete Element analysis an indispensable tool of scientific investigation. The current work provides a better understanding of the mechanics of mixing and segregation in a horizontally agitated paddle mixer via the Discrete Element Method, specifically focusing on the effects of particle size distribution, inter-particle adhesive forces and contact elasto-plasticity. A meso-scopic modelling approach is adopted using bi-sphered DEM elements to account for the non-sphericity of physical particles. Simulations with a very large number of particles are performed using GPU acceleration on an NVIDIA Quadro GV100 chipset to study the effect of particle size distribution on the mechanics of the system. The computational efficiency of this approach is explored by considering benchmarks and the results are included in this work. An innovative method for accessing and manipulating DEM data via the python scripting library EDEMPy is employed to calculate and visualise the spatial and temporal evolution of the mixture as well as important physical quantities such as the particle-particle contact forces and the kinetic energy distribution.

This work provides valuable insight into the mixing process of fine solids in paddle mixers and can be used to inform the design and scale up of such equipment, reducing the need for pilot studies and speeding up the design and optimization process. 36



Clovis Maliska Jr – ESSS Group

Clovis is the President and co-founder of the ESSS Group, a multinational company dedicated to the development and marketing of engineering simulation technologies and solutions. He has more than two decades of experience managing complex R&D projects for large companies on sectors such as oil & gas, aerospace and mining, as well as the development of simulation software encompassing techniques such as CFD, FEA and DEM. With a strong focus on computational sciences, numerical methods, human-machine interface and data visualization & analysis, Clovis’ vision is always to create the best simulation tools in terms of computational performance and modeling fidelity, as well as user workflow and productivity.

Next generation DEM Technology using Rocky: Some examples and case studies of blending, mixing and segregation in practical applications

Over the last decade, with the advent of faster computers, DEM technology has improved to such an extent that it is now possible to design large scale industrial processes in a practical amount of time. This presentation will cover some of these technology advancements, and how they can be applied to troubleshoot, predict and design systems such as blenders, hoppers and other process equipment using Rocky DEM and ANSYS.

37


Day Two -Afternoon Session-U Parkhotel Room C2

Paul Mort-Keynote Speaker

Purdue University (ex P&G)

Paul R Mort III Professor Department of Materials Engineering Center for Particulate

Products and Processes (CP3) FLEX Lab 3021B, Gates Rd, West Lafayette, IN 47906

Paul Mort recently joined Materials Engineering faculty in support of Purdue’s Center

for Particulate Products and Processes (CP3). He is a 24-year veteran of the Procter &

Gamble Company and is globally recognized as an expert in particulate processing

and powder technology. He has a demonstrated history of product innovation and

driving process efficiency in the consumer goods industry. Paul is an Editor for

Powder Technology journal and consultant with the International Fine Particle

Research Institute (IFPRI), working to develop a pipeline of perspective articles for

the journal. He is active in linking particle technology with adjacent technical

communities including pharmaceutical processing, materials science and

engineering, and process control.

Powder flow and cohesion – balancing industrial and academic perspectives of

processing and product design

38



Patrick Verolme

Delft Solids Solutions

Patrick Verolme studied Chemistry in Rotterdam and received his Bachelor of

Science degree from the Rotterdam Hogeschool, after performing his

graduation study at Delft Solids Solutions on the topic of water vapor sorption

studies. Since 2012 Patrick has been working at Delft Solids Solutions in the field

of solid particle / powder research, with his main area of expertise being

specific surface area, porosity and vapor sorption studies. His role has expended

to the research of bulk powder characteristics, including segregation, dustiness

potential, stickiness and attrition & abrasion of solid materials. He is a frequent

speaker on these bulk solids topics on seminars and courses.

Experimental assessment and quantification of segregation by means of

hopper segregation, sifting segregation and vibration segregation set-ups.

In this contribution we demonstrate the application of such set-ups for

identifying the segregation potential of powder blends based on differences in

particle size and density. To that end, we also use an algorithm to quantify the

segregation in each of the set-ups allowing a fair comparison among the various

set-ups but also among different formulations.39



Tong Deng

(Presented by: Mike Bradley)

The Wolfson Centre for Bulk Solids Handling Technology

Influences of Flowability and Permeability on Air Elutriation Segregation of

Pharmaceutical Powders

Segregation in bulk solids is an undesirable phenomenon, in which particle size distribution

varies at different location in a storage vessel causing significant changes in handling

processes due to a number of mechanisms. One influence factor is airflow when the

powders are handled in loading and offloading processes. Due to air flow, fine particles

move differently from coarser ones, causing changes of particle distributions within the

batch. This size change can be critical to industries including pharmaceuticals and food,

compromising quality of final products and leading to failures in quality control. In order to

control segregation, it is important to understand segregation mechanisms and the

influence factors such as material physical properties.

In this study, air induced segregation of pharmaceutical powders has been studied by using

an ASTM elutriation tester. 3 size grades of Lactose and one grade of Mannitol have been

used for segregation study. These materials have flow functions ranging from free flowing

to slightly cohesive. Also, permeabilities of the materials have been measured and

fluidisation air velocities have been determined. The results show interesting linkages

between material segregation behaviours and these material physical properties. The

reasons for the linkage are thought to be due to the principle that segregation of powders

may be controlled by adhesion forces and number of contacts between particles, so

adjusting or selecting these carefully could be a useful technique in control of material

segregation. 40



Naveen Mani Tripathi

Granutools

Dr. Tripathi is currently working as a Particle Scientist in GranuTools, Awans, Belgium. He completed his Ph.D. from Ben-Gurion University of the Negev, Israel and Masters’ from Thapar University, India in the area of Powder Technology. He has more than 7 years of research experience in this area and actively working as reviewer for many Scopus journals, such as Powder Technology, Particulate Science & Technology, Heliyon etc. He dealt with many international projects and published more than 10 research articles in Scopus journals and presented his research in more than 15 international conferences around the globe.

Physical characterization of powder blends with a focus on electrostatic properties

Blending and segregation are two opposite processes in bulk material handling. Therefore, we can say that these are two sides of the same coin. The triboelectric charges are produced during blending and segregation process at the contacts between the grains and as well as between the grains and the container. Unfortunately, this triboelectric effect is not fully understood, even at the fundamental level. The approach to solve practical problems is mostly empirical. Moreover, reproducible electrostatic measurements are difficult to perform. In the present study, the tribo-electrification of a set of excipients and active pharmaceutical ingredients (APIs) has been analyzed during the flow in contact with different materials. This behaviour is analyzed with a recently developed instrument called GranuCharge. The obtained charge density is found to depend on the material in contact. While different excipients have almost the same triboelectric behavior and a low chargability, APIs show complex triboelectric properties. Some APIs charge a lot while other APIs charge less. Afterward, the electrostatic behavior of API/ excipient blends is considered. It is found that the net charge of the blend is a complex function of the relative quantity of API in the mixture and the hygrometric conditions of the air. Moreover, both the quantity and the sign of the charge are found to depend on the material in contact with the powder during the flow. Finally, a relation between electrostatic charges, flowing (GranuDrum measurement) and packing (GranuPack measurement) properties will be discussed

41



Olukayode I. Imole

Hosokawa Micron B.V.

Olukayode I. Imole (Kay) works as a process technologist in the research and development department of Hosokawa Micron B.V., The Netherlands. Prior to this, he was a post-doctoral research fellow in the Multi-Scale Mechanics group, chaired by Prof. Stefan Luding at the University of Twente The Netherlands. In 2014, he received his PhD in computational sciences and engineering from the same University as a Marie Curie fellow. He also received a DAAD fellowship for the completion of his MSc degree in quality, safety and environment at the Otto-von-Guericke University , Magdeburg, Germany, where he worked on the synthesis of nanoparticles at the mechanical process engineering group of Prof. Jürgen Tomas. With a background in mechanical engineering, his current research interests are in all aspects of mixing, drying and agglomeration.

(see next page for abstract)

42



Olukayode I. Imole

Hosokawa Micron B.V.

(Continued)

Effect of process variables and material flow on filling consistency and final performance of lactose-based dry powder inhaler formulations.

Targeted delivery of highly potent, complex, low-dose of active pharmaceutical ingredients (API) into the pulmonary tract using dry powder inhalers (DPIs) is a common option for treating respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD) and Asthma. In typical DPI formulations, one or more micronized (1-5 microns) active pharmaceutical ingredients (APIs) are blended together with a coarse excipient such as lactose, which acts as a carrier. Ternary formulations including mixing of different excipients are also becoming increasingly popular. To obtain a final drug formulation that produces the desired efficacy, it is known that equipment selection, equipment operating variables, material flow characteristics and filling consistency (into blisters or capsules) are of critical importance. However, not much research has been done to investigate the interplay between these factors.

The aim of the present investigation is to understand the correlation of machineoperating variables and blend flow properties to the filling consistency and finalperformance of different lactose-magnesium stearate-based dry powder inhalerformulations. The Cyclomix® – a vertical high shear, high impact mixer – is used toperform the blends. It is expected, among others, that the results would helpformulators in making critical decisions during the early phases of drug developmentand also for post-approval changes.

43

Poster Abstracts for the Conference

Evaluation and Prediction of Blending Performance in a Continuous Direct Compression Line

B. Bekaert1, B. Van Snick2, K. Pandelaere1, J. Dhondt3, G. Di Pretoro², V. Vanhoorne1, T. De Beer3; C. Vervaet1

PURPOSE

The aim of the current study was to link blend properties with the blending performance on a continuous line for direct compression and to build empirical predictive models to select blender and tablet press configurations in function of the required tablet properties. This approach should allow to reduce the resources and amount of active pharmaceutical ingredient (API) needed during early drug product development phases.

METHODS

Based on principal component analysis (PCA) 30 tertiary blends with unique properties were selected and processed on a continuous direct compression line (CDC-50, GEA Pharma Systems). The experimental design focused on the configuration and speed of the main blender, while tablet weight was kept constant and no control loops were active. A partial least square regression (PLS) model was calibrated using the blend properties and blender/tablet properties were related to bulk residence time, residence mass and strain (of the blender), tablet weight variability. External validation was performed by processing additional blends to evaluate the predictive performance of the developed model. Additionally, blend uniformity was determined based on dynamic calibration models and linked to content uniformity deviations.

RESULTS

Bulk residence time, strain and residence mass (R² = 0.91, 0.90 and 0.91, respectively) were significantly influenced by process parameters (i.e. impeller speed), equipment configuration (i.e. the number of radial mixing blades) and blend properties (i.e. bulk and tapped density, true density), while the tablet properties were directly correlated with the blend properties (R² = 0.63). Model predictivity for new blends at different blender configurations was high (i.e. prediction error ranging from 0.3% to 41%). In-line near infrared (NIR) probes (i.e. Sentroprobe and GEA Light House Probe) used for blend uniformity measurements had difficulties measuring formulations with a potential for segregation and showed window fouling, which could result in over/underestimation of the API concentration in the blend.

CONCLUSION

The study established a direct link between blend properties and blending/tableting performance. External validation indicated that optimal process settings for new formulations could be predicted based on the blend properties. Measuring blend uniformity via PAT probes was challenging due to inherent blend properties, whereas these properties can influence the final acceptance criteria for content uniformity.

ACKNOWLEDGEMENTS

VLAIO and Janssen Pharmaceutica are acknowledged for co-funding the study.44


Fluidization of Nanopowders: Effects of Vibration and StirringFuweng Zhang

Due to strong inter-particle interactions (such as Van der Waals, electrostatic and moisture-induced surface tension forces), fluidization of most nanoparticles is difficult to achieve, which may require the introduction of external forces. In this study, we investigate both mechanical vibration and stirring to enhance the fluidization of nanopowders. Hydrophilic nanosilica is used as the testing nanopowders, which shows strong agglomeration behavior leading to poor fluidization hydrodynamics. Compared to using a stirring blade in previous studies, we use a fishbone structure as the stirring bar. This modification can greatly reduce the possibility that induces flow turbulence in the fluidized bed and particles’ attaching to the blade surface as a result of using the blade which has a relatively big surface area. Effects of the vibration direction (horizontal or vertical), vibration conditions (amplitude range from 0.5 to 5 mm and frequency from 20 to 60 Hz) and rotational speed of the stirrer (range from 30 to 200 r/min) on the fluidization quality of nanoparticles, the agglomerate formation, pressure drop curve, bed expansion, and the minimum fluidization velocity, have been experimentally investigated.

45


Presenter: Jeseung Moon

Blast furnace charging: segregation of multi-component mixtures

Jeseung Moon1, Yusong Pang1, Allert Adema2, Jan van der Stel2 and Dingena Schott1

Section of Transport Engineering and Logistics, Department of Marine and Transport Technology, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Mekelweg2, 2628CD Delft, The Netherlands

Research and Development, Tata Steel Europe, PO Box 10.000, 1970 CA IJmuiden, The Netherlands

[email protected], [email protected], [email protected], [email protected], [email protected]

Operating a blast furnace is finding the right balance between maximizing the reducing gas flowing upwards and decreasing the coke rate on the one hand and keeping the burden descend stable on the other. To achieve this, the permeability has to be optimal as well as the contact between the reducing gas and the iron ore. Therefore, the structure and composition of the packed bed are crucial. The bed is formed with multi-component mixtures of poly-disperse ferrous materials, nut coke and additives. These materials significantly differ in nature, shape, size and density. However, due to those particular characteristics, segregation takes place which influences the final structure and composition of the burden. Indeed, segregation has an effect on the process performance and the resulting blast furnace efficiency. Therefore, understanding and controlling the segregation problem during the charging process is the challenge for improving the productivity, stability and efficiency of the blast furnace.

Segregation is the phenomenon that a mixture made of particles of different dimensions and densities will always tend to separate, grouping the particles of one size in one area, and the particles of another size in another area. Therefore, segregation has to be dealt with by understanding the material properties and optimizing the charging sequence. Charging of blast furnaces has been studied using particle-based modelling techniques such as DEM to model burden layer formation and charging systems. Although for modelling realistic behaviour the calibration of the raw materials is crucial; this is an aspect that has not been covered well in these studies. Some studies omit material calibration, use simplified particle sizes or shapes, consider segregation of only single material components while in reality multiple components (iron ore pellets, sinter, nut coke and additives) are charged in one flow. So, a more realistic representation is required for understanding segregation of multi-component mixtures.

In this work, we will show the approach to establish validated numerical models predicting segregation of binary, ternary and quaternary mixtures in large-scale material handling to allow control towards higher process efficiency in the blast furnace.

Keywords: Segregation, Numerical Model, Discrete Element Method, Multi-component mixture, Charging Blast Furnace

46


47

Presenter: Hao Shi


48 Figure 2. (left) Final packing fraction 𝜂∞ depending on the fraction of small beads f for different size

ratios α. The different curves represent the corrected Furnas model fitted on the data of the same color.

The black curve represents the original Furnas model. (right) Typical time of compaction 𝜏 depending on

the size ratio 𝛼 for a fixed 𝑓 = 0.2. The color code is the same for both graphics.

Granular properties improved by polydisperse mixturesSalvatore Pillitteri1,*, Geoffroy Lumay1, Eric Opsomer1 and Nicolas Vandewalle1 1 GRASP, Institute of Physics, Building B5a, University of Liège, 4000 Liège, Belgium.*[email protected] study and the modelization of polydisperse mixtures is of great interest for the handling of granular media. Indeed, the properties like the packing fraction and the flowability of a powder are crucial in many field such as the pharmaceutical industry and construction. The compaction of granular materials is a popular method to characterize these two properties [1,2]. In our study, we focused on binary mixtures of spherical glass beads as model systems. We analyzed the packing fraction and the compaction dynamics depending on the mass fraction of small beads f and the size ratio α=d_L⁄d_S , d_L and d_S respectively the diameter of large and small beads. One can observe that binary granular mixtures increase their maximal packing fraction η_∞ with the size ratio of the beads. The evolution of η_∞ with f can be estimated by geometrical arguments based on the Furnas model [3,4], as seen on the left of Figure 2. Moreover, we observed a diverging typical time of compaction close to a critical size ratio α^*≈5.5, as shown on the right of the Figure 2. This divergence appears in the vicinity of the percolation threshold α_c=3+2√3, when small particles can pass through the voids left by the large ones [5].

mailto:*[email protected]


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Granular properties improved by polydisperse mixtures(Continued)Salvatore Pillitteri1,*, Geoffroy Lumay1, Eric Opsomer1 and Nicolas Vandewalle1 1 GRASP, Institute of Physics, Building B5a, University of Liège, 4000 Liège, Belgium.*[email protected]

References

[1] Lumay, G. et al. Measuring the flowing properties of powders and grains. Powder Technol. 224, 19–27 (2012). [2] Lumay, G., Vandewalle, N., Bodson, C., Delattre, L., & Gerasimov, O. Linking compaction dynamics to the flow

properties of powders. Applied physics letters 89, 093505 (2006). [3] Furnas, C. Grading aggregates-i.-mathematical relations for beds of broken solids of maximum density. Ind.

Eng. Chem. 23, 1052–1058 (1931). [4] Prasad, I., Santangelo, C. & Grason, G. Subjamming transition in binary sphere mixtures. Phys. Rev. E 96, 052905

(2017). [5] Pillitteri, S., Lumay, G., Opsomer, E., & Vandewalle, N. From jamming to fast compaction dynamics in granular

binary mixtures. Sci. Rep. 9, 7281 (2019).

mailto:*[email protected]

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Author and Presenter: Mitchel Post


51

Author: Peter HosonPresenter: Theresa Hörmann


Author and Presenter: Laure Descamps

52

Development of a methodology for predicting tablet press punch sticking L. Descamps1, J. Dhondt2, A. Kumar2, J. Bertels2, C. Vervaet3, D. Klingeleers2, T. De Beer1

1 Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences,

Ghent University

2 Janssen Research and Development, Division of Janssen Pharmaceutica NV

3 Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University

PURPOSE

During tableting, powder sticking can lead to the build-up of powder layers on the tablet press punches

with tablets with bad quality attributes as result. When punch sticking occurs, production needs to be

stopped for cleaning which can be problematic. Sticking often only occurs during prolonged production

runs making potential punch sticking issues undetected during the early development phase. Therefore,

tools that allow to predict the risk for punch sticking are required to timely optimize the formulation and

process, to avoid these problems in the production stadium. Sticking happens when the adhesion forces

between powder and tablet punch exceed the cohesion forces inside the tablet. It is a complex

phenomenon with several influencing factors such as material, formulation, process and environmental

dependencies. This study aims to initiate the development of a material- and time sparing methodology to

predict and quantify sticking propensity during large scale compaction based on material properties,

adhesion forces (both particle and bulk level) and process conditions.

MATERIALS AND METHODS

In this study, a full material characterization of powder properties and surface properties of 32

compounds, both excipients and API’s, was conducted. Whereas one single factor in isolation can not

explain sticking propensity of a compound by itself, over 100 raw material descriptors were determined

related to particle size and shape distribution, specific surface area, bulk, tapped and true density,

compressibility, electrostatic charge, moisture content, hygroscopicity, permeability, flowability and wall

friction [1]. The first step in the analysis of sticking propensity, is the measurement of the adhesion force

at particle level using contact mode atomic force microscopy (AFM) with the colloidal probe method [2].

Herewith, to imitate the interaction between the tablet punch and powder particles, metal plates of

stainless steel were used as scanning surface. For each material, 3 particles were selected to be as

representative as possible for the sample based on particle size and particle shape. Adhesion forces were

determined at three different locations on the metal plate as calculated from the measured force-distance

curves.

RESULTS & DISCUSSION

In this phase of the research, material characterization has been completed and 4 materials, Ibuprofen,

mannitol, sorbitol and microcrystalline cellulose, are subjected to AFM to evaluate the proof of concept.

These materials were chosen based on Principal Component Analysis (PCA) of the material properties

and taken their sticking propensity into account. Ibuprofen which is seen as model component for

sticking, shows the highest adhesion force. Although the method still needs some optimization, AFM has

proven to be a potential method to predict sticking. In the future, particle level measurements with AFM

will be linked to adhesion force measurements at bulk level including process parameters such as

tableting speed and compression force. Moreover, a more direct method to measure sticking will be

developed. This new information will be used to further develop the envisaged predictive platform based

on the most important material properties measurements, adhesion force, process parameters and blend

composition and adding more materials.

REFERENCES 1. Van Snick, B., Dhondt, J., Pandelaere, K., Bertels, J., Mertens, R., Klingeleers, D., ... & Vanhoorne,

V. A multivariate raw material property database to facilitate drug product development and enable

in-silico design of pharmaceutical dry powder processes. International journal of pharmaceutics,

549(1-2), 415-435 (2018).

2. Bunker, M., Zhang, J., Blanchard, R., & Roberts, C. J. (2011). Characterising the surface adhesive behavior of tablet tooling

components by atomic force microscopy. Drug development and industrial pharmacy, 37(8), 875-885.


53

Creating a cluster A recently added feature in MercuryDPM allows the user to create particle agglomerates which can be used to simulate dual porosity problems. By tuning µs, δ and σs, it is possible to obtain different values for equivalent stiffness and cluster radius.

µs δ

σs R K

= 0.0 = 0.1

= 0.1 = 8.02

= 3.46 · 103

Input parameters:

µs = 0.5 δ = 0.1

σs = 0.0 R = 7.95

K = 6.04 · 103

µf = sliding friction coefficient, δ = plasticity

Cloud of points representing the

preparation process of one cluster (snip)

depth, σs = size standard deviation. Output parameters: R = mean relative cluster radius, K = equivalent stiffness.

Outlook Current activities:

• Parameter calibration

• Simulating isotropic compression

• Analysis of micro- and macro-porosity

• Simulating salinization under isotropic conditions

Long-term goal: 1-D compression of clays with distilled water and saline water.

Distilled water Saline solution

MercuryDPM clusters: toward the application to dual porosity materials

P. Rapino, L. Orefice, A. R. Thornton, T. Weinhart, G. Musso, V. Magnanimo Multiscale Mechanics, Department of Thermal and Fluid Engineering, ET/Mesa+

University of Twente. [email protected]

µs δ

σs

= 0.5 = 0.1

= 0.1

µs δ

σs

= 0.5 = 0.3

= 0.1 R = 8.04 R = 7.19 K

= 8.01 · 103 K = 3.97 · 104

Adhesive elasto-plastic contact model [1]

e eM σsper. e eM σsper.

(kPa) (kPa)

0.96 0.35 500 0.72 0.43 500 0.93 0.33 1000 0.68 0.4 1000

0.85 0.28 2000 0.60 0.33 2000

Application: dual-porosity materials (clays) Varying the plasticity depth it is possible to simulate packings with different micro-porosity em and macro-porosity eM which are associated for example to different interstitial fluids clays. [2]

δ = 0.1: large em, small eM δ = 0.3: small em, large eM

References and acknowledgments [1] S. Luding, Cohesive, frictional powders: contact models for tension, Granular Matter, 10, 235-246 (2008) [2] G. Musso, E. Romero and G. Della Vecchia, Double-structure effects on the chemo-hydro-mechanical behaviour of a compacted active clay, Geotechnique, 63(3), 206-220 (2013)

Author and Presenter: Paolo Rapino

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Author and Presenter: Hongyang Cheng

55


Author: I.F.C. DenissenPresenter: Anthony Thornton

56


Author: Zengyuan Wang

INVESTIGATING RESIDENCE TIME DISTRIBUTION (RTD) OF POWDER BLENDING USING

TANKS IN SERIES (TIS) MODEL Zengyuan Wang*,** – Bram Bekaert*** – Thomas De Beer** – Ingmar Nopens**BIOMATH, Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.**Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium***Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium

In recent years, the pharmaceutical industry is facing challenges with regard to the transition from batch to continuous manufacturing. The latter has been applied in other industries for decades, showing significant advantages. Residence time distribution (RTD) models have long been used to describe continuous processes in a wide variety of applications as they characterize the dispersion of the materials inside the system. More recently RTD approaches have been applied to continuous powder feeding and blending processes, which are of interest in pharmaceutical manufacturing (van Snick et al., 2019, Sebastian Escotet-Espinoza et al., 2019). Screw blenders are integrated as crucial mixing units in most continuous pharmaceutical processes. Hence, characterizing and modelling the RTD of materials in blenders is essential to understand the material traceability and to isolate intermediate materials or end products when specifications are not met.

A pulse experiment with 5% w/w tracer was performed to acquire the RTD data of a screw blender. The mostly widely used RTD model in powder systems in the literature (Sebastian Escotet-Espinoza et al., 2019), tanks-in-series (TIS) model is presented and used to describe the experimental data. The modeling parameters that were examined include the delay time, the average residence time in all tanks and the number of tanks.

The results show that the TIS model is suitable for gaining understanding of the dynamics of continuous mixing with different process settings. The observed correlations can potentially be used to predict the parameters of the tanks-in-series model at different Froude number for a given throughput. More validation work should be performed to examine whether this observed relationship remains over a wide range of different operating conditions.

57


Author: M.W. Bennett

The effect of production press stiffness on tablet strain rateBy: M.W. Bennett

The structural integrity of a tablet may be damaged by stress cracks if the rate of load release is faster than the tablet is able to stress relieve itself through elastic and plastic recovery. High power Compaction Simulators allow the study of production speed strain rates, but to do this requires simulation of the elastic behaviour of the production press. Elastic properties of the tooling are common to the production press and the Compaction Simulator. This poster quantifies the effect of typical press elasticity values on the theoretical strain rate using typical tablet loading data.

58


Author: M.W. Bennett

Simulation of load limiting presses using a Compaction Simulator

By: Martin Bennett (Huxley Bertram) and Frederik Detobel (GEA)

Load limiting tablet production presses are increasingly used in “continuous tableting” production lines. Simulation of these presses is required to allow efficient and material sparing methods to be used in formulation development for continuous production. Complex control methods in Compaction Simulators can allow instant switching from “position control” to “load control” and vice-versa during highly dynamic loading events.Huxley Bertram and GEA are working on developing the techniques to simulate load relieving production presses accurately, and the first round of results are presented in this paper.

59


Author: Naveen Tripathi

Influence of flowing agents addition on excipient flowability

Naveen Mani Tripathi1, Filip Francqui1, Geoffroy Lumay2

1Granutools, Rue Jean-Lambert Defrêne, 107, 4340 Awans, Belgium2University of Liège, Allée du 6 août, 4000 Liège, Belgium

The measurement of the physical properties of powders is very much important because with the help of these properties, we can easily define them. To control and optimize the powder processing methods, it is very important to precisely characterize these materials. In the present poster, we show how recently developed powder flowability measurement method (Granuflow) can be used to measure the influence of flow aid additives on an excipient.In this research, Pharmatose 200M is used as an excipient. To increase the flowing behavior of this excipient, four different flowing agents are selected: Hydrophilic amorphous silica (Sipernat500LS and 50S) and Hydrophobic amorphous silica (Sipernat D10 and D17). GranuFlow instrument is utilized to measure the flowability of all blends (mixture of excipient and flowing agents).It is found that virgin Pharmatose 200M powder is unable to pass through any aperture of the GranuFlow. For a mass fraction of 0.5% of 500LS and D17 flowing agents, only two holes allow the powder to flow. For Sipernat 500 LS, D10 and D17 addition, the more flowing agent percentage (until 2%), the better flowability. However, for Pharmatose 200M with Sipernat 50S additive, a significative flowability improvement is achieved with an additive of 2% flowing agent. Indeed, 0.5 and 1% additions yield to similar results.

We show that flow aid additives induce the improvement of powder flowability, which is well measured by GranuFlow. Moreover, the efficiency of the different additives is compared and the effect of the concentration is evidenced.

http://www.granutools.com/

60


Authors: D.R. Tunuguntia,A.R.Thornton, S. Luding, T. Weinhart

Presenter: A.R. Thornton

BLENDING & SEGREGATION FORUM BSF2019-EU...BLENDING & SEGREGATION FORUM BSF2019-EU The Scientific Conference portion of the Forum (Tuesday & Wednesday) features distinguished keynote

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