Abstracts:
Posters:
Grant: Predictive formulation of high-solid-content complex dispersions
PIs: Dr Jin Sun, University of Edinburgh & Dr Mark Haw, University of Strathclyde
Force distribution and contact network analysis of sheared dense suspensions
Rangarajan Radhakrishnan, John Royer, and Jin Sun
School of Engineering, University of Edinburgh
Force Distribution and Contact Network Analysis of Sheared Dense Suspensions
Rangarajan Radhakrishnan1, John R. Royer2, Wilson C. K. Poon2, and Jin Sun1
1 Institute of Infrastructure and Environment, School of Engineering, The University of Edinburgh, Edinburgh EH9 3JL, UK
2 School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3FD, UK.
Contact Email:
Dense suspensions of particles in a fluid are used in formulations of products such as paints, ceramic pastes, and cements among others. Understanding the rheology of such suspensions is essential for their manufacture, transport or use. Dense suspensions of stabilised particles often exhibit shear thickening, where there is a large increase in viscosity with increase in applied stress. Here, we seek to understand suspension rheology by taking advantage of their relation with the physics of jammed granular materials.
Dense suspensions of non-Brownian spheres in a Newtonian fluid are studied using discrete element method (DEM) simulations. The contact force network properties of suspensions of particles with different friction coefficients and volume fractions are examined. We find that suspensions exhibit several similarities with jammed granular materials. As suspensions approach the jamming point, the relation between extrapolated values of jamming volume fraction and average contact number of particles in flowing suspensions are quantitatively close to those obtained from the simulations of isotropically compressed and sheared grains. Similarly, the distributions of contact force in suspensions is close to that of granular packings. These findings suggest potential refinements to the mean field models used to understand the rheology of shear thickening suspensions.
The rheology of dense suspensions of mixtures of frictional and frictionless particles
Yang Cui, Rangarajan Radhakrishnan, John Royer, and Jin Sun
School of Engineering, University of Edinburgh
Rheology of non-Brownian suspensions composed of frictional and frictionless particles
Yang Cui1, Rangarajan Radhakrishnan1, John Royer2, and Jin Sun1
1 School of Engineering, University of Edinburgh, Edinburgh, United Kingdom
2 School of Physics and Astronomy, University of Edinburgh, Edinburgh, United Kingdom
Contact Email:
To better understand and tune the viscosity of dense suspensions, we perform numerical simulations of dense suspensions composed of frictional and frictionless particles. We show that adding frictionless particles to suspensions of frictional particles decreases the relative viscosity of suspensions as a result of increased jamming volume fraction. However, the viscosity reduction is not as significant as that shown in experiments of colloidal suspensions containing rough and smooth particles, which means that the friction coefficient alone is probably insufficient to describe the effect of particle roughness. Furthermore, we examine the limiting cases when the contact between a frictional and a frictionless particle of the binary suspension is treated as purely frictional or frictionless. It is found that the relationship between jamming volume fraction and the fraction of all contacts that are frictional (f) between the two cases are different. This indicates that the scalar variable f, based on mean-field assumption of contacts, is inadequate in predicting the rheology of such binary systems.
Jamming in adhesive granular suspensions
James Richards, Wilson Poon et al.
School of Physics and Astonomy, University of Edinburgh
Friction and Adhesion in The Jamming of Non-Brownian Suspensions
James Richards, Michiel Hermes, Ben Guy, Elena Blanco, Guilhem Poy and Wilson Poon
SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, UK
Suspensions of hard particles in a background solvent are ubiquitous in industrial processing, where there is a drive to higher volume fractions to improve efficiency and product performance. This can be prevented by suspensions becoming highly non-Newtonian and difficult to predict, for example developing a yield stress highly sensitive to volume fraction. We study the transient rheology of a model yield-stress suspension, cornstarch in oil. Three steps are identified: adhesive bond breakage at low strain; jamming from compressive frictional-contact-network formation at higher strain; and finally, with sufficient stress, contact-network buckling to a flowing state. The stress of this final ‘unjamming’ step diverges below random close packing, revealing the key role of friction and suggesting novel ways to tune yield-stress suspensions, e.g. modifying inter-particle friction.
Squeeze flow rheology of highly concentrated suspensions
Jose Antonio Ruiz-Lopez (*), John Royer (**), Mark Haw (*) and Wilson Poon (**).
* Department of Chemical and Process Engineering, University of Strathclyde, James Weir Building, 75 Montrose St., Glasgow, G1 1XJ
** School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh, EH9 3FD.
Squeeze flow rheology of highly-concentrated suspensions
Jose Ruiz-Lopez1, John Royer2, Mark Haw1 and Wilson Poon2
1 Department of Chemical and Process Engineering, University of Strathclyde, James Weir Building, 75 Montrose St., Glasgow, G1 1XJ.
2 School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh, EH9 3FD.
Shear-thickening behaviour is often found in highly-concentrated suspensions of repulsive particles. The viscosity of these suspensions increases with the shear rate. Depending on the concentration, there could be a continuous (low or intermediate concentration) or discontinuous shear-thickening (high concentration). When the concentration approaches a certain value, i.e. the critical or jamming concentration, the high-rate viscosity diverges and the system jams. This behaviour has been recently explained by frictional contacts between particles. This theoretical framework has been corroborated by experiments and molecular dynamic simulations [1-2]. However, industrial applications using shear-thickening fluids often exert non-shearing flows. Thus, it is important to understand the behaviour of these fluids under both shear and extensional flows.
Hence, this study aims to understand the flow properties of shear-thickening suspensions under squeeze flow with no-slip boundary conditions. It is a complex flow with a shear and a biaxial extensional component. In order to understand the mechanics of this flow, we first use Newtonian fluids and the normal force were fitted to theoretical models taking into account the roughness of the plates [3]. Later, this analysis was extended to concentrated suspensions. Considering the second invariant of the rate-of-deformation tensor for the shear component, the onset of the thickening was very similar to our shear results. However, there was a slight decrease in the critical concentration, in good agreement with recent molecular dynamic-simulations for biaxial extensional flows [4].
[1] Lin NYC, Guy BM, Hermes M, Ness C, Sun J, Poon WCK and Cohen I (2015) Phys. Rev. Lett., 115(22): 228304.
[2] Mari R, Seto R, Morris JF and Denn MM (2014) J. Rheol., 58(6): 1693-1724.
[3] Meeten GH (2004) Rheol. Acta, 43(1): 6-16.
[4] Cheal O and Ness C (2018) J. Rheol., 62(2): 501-512.
Grant: Formulation for 3D printing: Creating a plug and play platform for a disruptive UK industry
PI: Professor Ricky Wildman, University of Nottingham
3D printing of a stimuli-sensitive multifunctional edible formulation
Azarmidokht Gholamipour-Shirazi, I.T. Norton, Tom Mills
School of Chemical Engineering, University of Birmingham
3D printing of a stimuli-sensitive multifunctional edible formulation
Azarmidokht Gholamipour-Shirazi1, Ian T. Norton1 , Tom Mills1
1 School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, B15 2TT
Contact Email:
The development of conductive hydrogel materials is necessary for the advancement of edible device research. Moreover, if hydrogel produces mechanical motion in response to electrical stimulus making it a good candidate for implementation of soft actuators. On the other hand, 3D printing (additive manufacturing) as a digital fabrication technology enables precise construction of complex objects directly from a computer-aided design (CAD) model. Here, we describe a new temperature and electric field dual-stimulus responsive hydrocolloid formulation for programmed drug delivery. The electrical and thermal release properties and 3D printability of hydrocolloid were studied. It was also found that this hydrogel produces mechanical motion in response to electrical stimulus.
The hydrogel was prepared by dissolving potassium chloride (0.5 wt. /v %) and for release studies, folic acid (0.05 wt. /v%) in deionized water at 80 ˚C under continued mixing followed by adding the mixture of kappa-carrageenan (1 wt./v%) and iota-carrageenan(1 wt./v%). The solution was held for 30 minutes in the water bath at 80°C with gentle stirring. A custom-built food 3D printing system was used in this study. Printing parameters were adjusted for each sample to get the optimum printability.
The hydrogel is conductive. The 3D printed hydrogel beam bends up to 12 ° while in the electric field. This shows that the hydrogel can be used as a soft actuator. Doughnuts with the diameter of 30 mm/4mm were printed and the folic acid release was studied at 37 ˚C. The results were compared with that of a casting sample and no major differences were observed. The electric field drug release was studied by printing hydrogel over the copper electrode and studying the release in PBS at room temperature. The release is increased by 4-6 times following applying the electric field. It shows that the hydrogel if loaded with a drug serves as a drug reservoir for electric-field- triggered release.
High–Throughput Determination of Printability for 3D Inkjet Formulations
Zuoxin Zhou, University of Nottingham
Grant: Evaporative Drying of Droplets and the Formation of Micro-structured and Functional Particles and Film
PI: Professor Colin Bain, Durham University
Particle Migration in Drying Droplets
Jack Goodall, L. Yang, C. D. Bain, Durham University
Particle Migration in Inkjet-Printed Droplets
G. J. Goodall1, L. Yang1, C. D. Bain1
1Durham University, Durham, UK
The evaporation of sessile droplets can be a useful method to pattern substrates, with inkjet printing technology being particularly good at the selective deposition of functional materials. A predictive understanding of formulations is necessary in order to design systems in which the internal flows generated during drying do not lead to undesirable non-uniform morphologies.1 Composition or temperature gradients across the liquid-vapour interface have been shown to induce Marangoni flows which can redistribute suspended material,2 however studies have mainly taken place on microlitre droplets.
Here we report experiments on the internal flows of inkjet-printed picolitre droplets in which high-speed cameras are used to follow the trajectories of light-scattering tracer particles and record the droplet profile. Solutal Marangoni flows are generated in a selection of solvent mixtures and solutions however at these smaller length-scales different morphologies are observed. Instead of obtaining uniform deposits, particles are seen to migrate across flow streamlines3 to collect in groups in ethanol-water mixtures, ethylene glycol-water mixtures and sucrose, lactose, sodium chloride and sodium nitrate solutions, demonstrating the prevalence of particle migration in a disparate range of chemical systems.
ACKNOWLEDGEMENTS: The authors acknowledge support from the Engineering and Physical Sciences Research Council under grant code EP/N025245/1.
Control of Ring Stains by Marangoni-Enhanced Spreading
Lisong Yang1, Guohua Hu2, Tawfique Hasan2 and Colin D. Bain1
1 Chemistry Department, Durham University, Durham, DH1 3LE
2 Cambridge Graphene Centre, Cambridge University, Cambridge, CB3 0FA
Control of Ring Stains by Marangoni-Enhanced Spreading
Lisong Yang1, Guohua Hu2, Tawfique Hasan2 and Colin D. Bain1
1 Chemistry Department, Durham University, Durham, DH1 3LE
2 Cambridge Graphene Centre, Cambridge University, Cambridge, CB3 0FA
Contact Email:
The coffee-ring effect (CRE) is ubiquitous in nature and functional printing, leading to non-uniform deposits that limit the performance of electronic and optoelectronic devices and impairs device-to-device consistency. The CRE is manifested as a ring-like deposit of solutes or suspended particles at the three-phase contact line (CL) where the edge of the liquid droplet meets the substrate. When the CL is pinned, a capillary flow from the droplet apex to the CL is observed that preserves the shape of a spherical cap. Dispersed solutes or particles are carried by the capillary flow and deposited at the CL, forming a ring stain. 2D crystals are promising materials for printed electronics and optoelectronics. This prospect, however, has been hindered by CRE. We present a universal strategy for generating uniform deposits of 2d crystals using Marangoni-enhanced spreading in binary solvent mixtures. Isopropanol (IPA) containing a small amount of a second alcohol, such as 2-butanol, is used. Enhanced evaporation of the more volatile solvent with a lower surface tension (IPA) at TPC leads to outward Marangoni flow from apex to contact line, which result in the enhancement of the spreading and delay of the contact line pinning. Surface stress increases radial outward velocity and leads to deviation from spherical cap. Lack of curvature in resulting ‘pancake’ means that there are no Laplace pressure gradients to drive capillary flows to the contact line – fluid flow slows down. Uniform deposit can be obtained. The strategy is generally applicable to other (stably suspended) particles on wettable substrates.
Crystallisation in Inorganic Solution Aerosol Droplets
Flo Gregson1, Rachael Miles1, Josh Robinson2, Paddy Royall1,2, and Jonathan Reid1
1 School of Chemistry, University of Bristol, BS8 1TS, UK
2 School of Physics, University of Bristol, BS8 1TS, UK
Crystallisation in Inorganic Solution Aerosol Droplets
Flo Gregson1, Rachael Miles1, Josh Robinson2, Paddy Royall1,2, and Jonathan Reid1
1 School of Chemistry, University of Bristol, BS8 1TS, UK
2 School of Physics, University of Bristol, BS8 1TS, UK
Contact Email:
The drying of droplets in the aerosol phase to form solid microparticles is of fundamental importance to a range of industries, particularly spray-drying wherein powdered products for pharmaceuticals, food and cosmetics are produced from rapidly drying an aerosolised feed solution. The resulting particle size, morphology and degree of crystallinity, whilst crucial for the desired product, can be very sensitive to the drying process, and hence to the processing conditions. In this work we are studying the propensity for crystallisation in a rapidly evaporating droplet, to understand what governs crystallisation or amorphous particle formation in a spray-dryer.
Using an Electrodynamic Balance (EDB) we levitate a single liquid droplet (radius ~ 25 µm) and collect the elastic light scattering pattern from a 532 nm laser that illuminates the droplet. Using the scattering phase function and the geometric optics approximation we can calculate the droplet radius throughout the drying process and distinguish between crystallisation and the formation of an amorphous particle.1 We can thus measure the drying kinetics and propensity to crystallise for droplets containing a range of inorganic salt solutions e.g. NaNO₃, KNO₃, NaCl) in different drying conditions. By the addition of co-components to the initial droplet solution we can induce, prevent or delay crystallisation in an evaporating droplet of an aqueous inorganic salt (see Fig.1). We thus present a step closer to ultimately predicting and controlling product morphology and degree of crystallinity in the products of spray-drying processes.
Figure 1: An example of a technique to delay crystallisation in a salt solution droplet in the EDB. A droplet containing NaCl (10% wt/wt), ethanol (45%) and water (45%) evaporates and crystallises at ~ 11 µm but with increasing amounts of a small addition of surface-active alcohol which reduces the evaporation rate, we delay the crystallisation time.
Acknowledgements: The authors acknowledge the funding support from the EPSRC under grant code EP/N025245/1.
References:
Gregson, F. K. A., Robinson, J. F., Miles, R. E. H., Royall C. P., and Reid, J. P., Drying Kinetics of Salt Solution Droplets: Water Evaporation Rates and Crystallization, J. Phys. Chem. B, 2018, 123, 266.
Grant: Enabling rapid liquid and freeze-dried formulation design for the manufacture and delivery of novel biopharmaceuticals
PIs: Dr Robin Curtis, The University of Manchestr & Professor Paul Dalby, University College London
Optical deconvolution of co-eluting protein species during chromatographic separation
John Hales, University College, London
Optical Deconvolution of Co-eluting Protein Species During Chromatographic Separation
John E. Hales1, Samir Aoudjane1, Hongyu Zhang1, Deniz Ucan1, Paul A. Dalby1.
1 UCL Department of Biochemical Engineering
We demonstrate a new optical technique for continuous monitoring of protein species as they are eluted from a chromatographic column even when they fully co-elute with other protein species and without making any assumptions about the elution profile. To achieve this, we designed and constructed a novel ##### chromatograph and established an analytical framework for deconvolving and quantifying distinct but co-eluting protein species. This technology has immediate relevance as an analytical tool for formulation studies.
A web tool for predicting protein solubility and solution properties from sequence and structure
Max Hebditch and Jim Warwicker, The University of Manchester
A web tool for predicting protein solubility and solution properties from sequence and structure
Max Hebditch1, Jim Warwicker1
1 School of Chemistry, University of Manchester
Contact Email:
Monoclonal antibodies are a promising biotherapeutic platform due to their high specifictity and selectivity, but as a result of their relatively large size, they must be formulated at high concentration for subcutaneous injection. Compared to small molecules, protein drugs are generally less stable and this instability can lead to batch to batch inconsistencies, or even immunogenic responses in the patient. To improve biopharmaceutical formulation stability, traditional approaches rely on experimental screens and targeted protein engineering, which can be a difficult and time-consuming process. Computational tools are increasingly popular, but require familiarity with multiple complex, and proprietary, software packages. To accelerate the design of biotherapeutic products, we present Protein-sol, a simple and free, web based suite of theoretical calculations and predictive algorithms for understanding protein solubility and stability. Protein-sol can predict solubility based on the sequence properties of a protein, or given a structure, calculates the surface distribution of charge and hydrophocity as well as the predicted stability at 91 different pH and ionic strength combinations.
Grant: INFORM 2020 - Molecules to Manufacture: Processing and Formulation Engineering of Inhalable Nanoaggregates and Microparticles
PI: Professor Darragh Murnane, University of Hertfordshire
Investigating Powder Cohesion And Surface Interaction Forces In Agglomerated Powders For Inhalation Drugs
Hien Nguyen, University of Leeds
Investigation of powder cohesion and surface interaction forces in agglomerated powders for inhalation drugs
Thai T. H. Nguyen1, Robert B. Hammond1, Darragh Murnane2, Kevin J. Roberts1
(1) Centre for the Digital Design of Drug Products, School of Chemical and Process Engineering, Institute of Process, Research & Development, University of Leeds, Leeds, LS2 9JT, UK
(2) School of Life and Medical Sciences, University of Hertfordshire, Hertfordshire AL10 9AB, U.K.
Corresponding author:
Asthma treatments using inhaled drugs were first marketed in the 1950s, and currently 'topical' or targeted treatments with inhaled drugs are common in the treatment of a variety of other lung diseases [1]. Dry powder inhalers (DPIs) usually contain drug particles <6 μm. Typically these particles either agglomerate or adhere to the surfaces of larger carrier particles often composed of a-Lactose Monohydrate. The detachment of drug particles from carrier particles and de-agglomeration of drug particles into single particles is crucial to the efficacy of inhaled medicines. Hence, there is a need to quantify inter-particulate interactions on a material and surface-specific basis.
In-silico characterisation as part of a digital design strategy can inform formulation development for inhaled medicines to maintain effective drug aerosolization in delivery devices. The study will describe in-silico approaches for predicting and, ultimately, engineering the agglomeration state of micro-particulate drugs. Representative materials investigated include α-Lactose Monohydrate (α-LMH) as an excipient and Terbutaline Sulfate (TBS) as an API. The initial work-flow, utilizing Synthonic Engineering tools [1], allows the characterization of bulk (intrinsic) interactions in terms of the strength and direction of the intermolecular interactions, calculation of lattice energy, attachment energy and crystal morphology together with identification of the dominant crystal faces and crystal surface-energy. In the subsequent work-flow, the surface (extrinsic) interactions are characterized using a systematic search method [2] to calculate the interactions energies of API/excipient molecules with API/excipient crystal surfaces. From this, the adhesive and cohesive interactions between API and excipient are characterized. The utility of such molecular modelling approaches as part of a digital-design strategy for inhaled medicines will be discussed.
Figure 1. Predicted (left) and observed (right) morphology of TBS single crystals grown in a mixture of 70% water and 30% ethanol at 5°C.
References
- Roberts, K.J., et al., Synthonic engineering: from molecular and crystallographic structure to the rational design of pharmaceutical solid dosage forms. Computational Pharmaceutical Solid State Chemistry, 2016: p. 175-210.
- Hammond, R.B., et al., An examination of binding motifs associated with inter-particle interactions between facetted nano-crystals of acetylsalicylic acid and ascorbic acid through the application of molecular grid-based search methods. Journal of Pharmaceutical Sciences, 2009. 98(12): p. 4589-4602.
A comparison of Eulerian-Eulerian and Eulerian-Lagrangian approaches for modelling the aerosolisation of fine powders
Xizhong Chen, University of Cambridge
A comparison of Eulerian-Eulerian and Eulerian-Lagrangian approaches for modelling the aerosolisation of fine powders.
Xizhong Chen and James A. Elliott
Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, UK
Delivering drugs directly to the lung through the respiratory tract is useful for the treatment of asthma and chronic obstructive pulmonary disease. The dry powder inhaler (DPI) has been introduced as a device for delivering drug particles to the lung. The dispersion behaviour of particles in dry powder inhalers depends on the gas phase flow and particle-particle/wall interactions. In this study, we applied both the Eulerian-Eulerian and Eulerian-Lagrangian approaches to model and analyse the dry powder dose fluidization and entrainment behaviours. A design-of-experiments approach was followed to calibrate the model input parameters. The simulation results were then compared with experimental high-speed video records. Good agreement between the Eulerian-Eulerian and Eulerian-Lagrangian methods was found for the prediction of non-cohesive glass particles. Moreover, the Eulerian-Lagrangian simulations can capture the entrainment behaviours of cohesive lactose powders observed in experiments. The advantages and disadvantages of both approaches for DPI simulations will also be discussed.
Fig. CFD-DEM simulation of dry powder entrainment process
Nano, Micro and Meso-scale characterisation of lactose powders using X-ray Computed Tomography
Parmesh Gajjar and Ioanna Danai Styliari, The University of Manchester
Nano, Micro and Meso-scale characterisation of lactose powders using X-ray Computed Tomography
Ioanna Danai Styliari1, Parmesh Gajjar2, Timothy L. Burnett2, Xizhong Chen5, James A. Elliott5, William J. Ganley6, Robert Hammond3, Hien Nguyen3, Robert Price4, Kevin Roberts3, Philip J. Withers2, Darragh Murnane1*
1 School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK.
2 Henry Moseley X-ray Imaging Facility, School of Materials, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK
3 Centre for the Digital Design of Drug Products, School of Chemical and Process Engineering, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
4 Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
5 Department of Materials Science & Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge, CB3 0FS, UK
6 Nanopharm Ltd, Cavendish House, Newport, NP10 8FY
The physical and chemical properties of the powder blend have a significant influence on the performance of a dry powder inhaler, with attributes such as size, shape and flowability playing critical roles at each stage of delivery. Of particular importance are the size and microstructure of the powders as they determine the deposition site in the respiratory tract. A number of methods currently exist for determining powder size and shape distributions, for instance Laser diffraction (LD), Scanning Electron Microscopy, (SEM), Optical Microscopy (OM), cascade impaction (CI), Raman microscopy (RaM), and atomic force microscopy (AFM). However all of these techniques suffer from low resolution, image in 2D projections, are based on shape assumptions, or require dispersion of the particles. As a result key information about the powder microstructure is lost.
In this work, we show how X-ray Computed Tomography can be an invaluable characterisation technique for inhalable formulations, with advantages of being fully three-dimensional, non-destructive and both micro- and nano-scale Micro-CT can provide valuable information on a powder blend, with size and shape statistics comparable with LD and OM data, whilst nano-CT can provide 150 nanometer resolution of single particles, allowing agglomerates and particle surfaces to be analysed. All of this information provides vital 3D information on the particle microstructure, and hence how the formulation behaves.
Figure A: Micro-CT of a single Lactohale 100 (carrier) particle. B: Nano-CT of a single agglomerate of Lactohale 300 (fines)
Grant: Complex ORAL health products (CORAL): Characterisation, modelling and manufacturing challenges
PI: Professor Panagiota Angeli, University College London
Rheology and Microstructure of Particle Suspensions in Oral Health Formulations
A. Papadopoulou, M. Tiwari, S. Balabani, University College, London
Rheology and Microstructure of Particle Suspensions in Oral Health Formulations
Anastasia Papadopoulou1,2, Manish K. Tiwari1, Stavroula Balabani2
1 Nanoengineered Systems Laboratory; 2 FluME
Department of Mechanical Engineering, University College London, London, WC1E 7JE, England
Particle suspensions are encountered in a range of healthcare and industrial formulations as well as biological systems. The rheology of particle suspensions is complex; characterised by non-Newtonian – often unpredictable – flow properties, such as yield stress, shear thinning and shear thickening, even in the simplest case of rigid spheres suspended in Newtonian media. These properties have been attributed to particle–particle interactions and changes in suspension microstructure which depend both on the particles as well as the suspending medium.
In this project, we aim to characterize the microscopic and macroscopic flow properties of dense, non-colloidal silica particle suspensions in non-aqueous media with a view to address manufacturing challenges of novel oral health formulations. Steady state shear experiments were conducted in suspensions of silica particles, commonly used as abrasives or fillers in novel toothpaste formulations. Particle morphology and surface roughness were found to increase suspension viscosity and induce non-Newtonian behaviour at lower particle volume fractions compared to suspensions of glass spheres. Oscillatory shear measurements and optical shearing techniques were employed to probe interparticle interactions and further elucidate the specific mechanisms that lead to the rich rheological phenomena of those complex particle suspensions.
Studies of the fluid dynamic behaviour of liquid-solid mixtures in agitated vessels
G. Meridiano, L. Mazzei, P. Angeli, University College London
Studies of the Fluid Dynamic Behaviour of Liquid-Solid Mixtures in Agitated Vessels
Panagiota Angeli, Giovanni Meridiano, Weheliye Hashi Weheliye, Luca Mazzei
ThAMeS Multiphase, Dept Chemical Engineering, University College London, London WC1E 7JE, UK
Mixing of solids in viscous liquids in stirred vessels is a crucial step in many manufacturing processes; it is regularly encountered in a wide range of industrial sectors including healthcare, pharmaceuticals, cement manufacturing and food processing. In many of these applications, the liquids have complex non–Newtonian behaviour that further complicates the mixing process. The objective of this work is to understand and characterize the fluid dynamics of liquid-solid mixtures with both Newtonian and non–Newtonian liquid matrixes in stirred vessels. A refractive index matching technique combined with Particle Image Velocimetry (PIV) and Particle Tracking Velocimetry (PTV) has been used to investigate the laminar mixing of a solid-liquid suspension in both Newtonian and non-Newtonian liquids. The combined techniques, together with an image analysis procedure, enable the simultaneous measurement of the liquid phase and the solid phase velocity field. A variety of fluids have been developed in order to explore different non-Newtonian behaviours. 1.5 mm PMMA spheres were employed as the suspended solid phase up to a volumetric concentration of 5%. The experimental investigation has shown remarkable differences between the Newtonian and non-Newtonian cases. In particular, the particles tend to accumulate at the core of the vortical structures of the flow when a non-Newtonian background fluid is employed.
Grant: Virtual Formulation Laboratory for prediction and optimisation of manufacturability of advanced solids based formulations
PI: Dr Csaba Sinka
Virtual Formulation Laboratory for prediction and optimisation of manufacturability of advanced solids based formulations
Sinka I.C., Ghadiri M., Heng J.YY., Bradley M.S.A., Davidchack R., Jia X., Berry M.R., Edmans B.D., Pasha M., Karde V., di Pasquale N., Kahrizsangi H.S. .
Predictive methods for the strength of powder compacts
Edmans B.D. and Sinka I.C., University of Leicester
Predictive Methods for the Strength of Powder Compacts
B. D. Edmans, I. C. Sinka
University of Leicester, United Kingdom
Contact Email:
A priori estimation of the mechanical strength of powder compacts for new formulations remains a very challenging task as the influence of particle size distributions, elastic stiffness, plasticity and adhesive properties is highly nonlinear. In this work, two theoretical frameworks for predicting compact strength, bond aggregation and fracture mechanics, are briefly reviewed, highlighting the need for empirical relations describing the “structural factor” (particle packing and the distribution of interparticle contact vector) as well as methods for calculating the “interaction factor”, in the form of interparticle contact relations describing the magnitude of forces exerted between particles and the development of contact zones. It is proposed that, in order to predict the “interaction factor” from particle-level properties accurately, contact laws need to incorporate particle compressibility. Systematic finite element studies were carried out investigating load-displacement relations and development of internal plastic zones for particles displaying internal compressible plasticity effects. Results are presented demonstrating that internal hardening can significantly affect load-displacement response at large compression. An empirical contact law is formulated to describe the responses, and the parameters of the contact law are related to particle-level properties.
Surface Energy Characterisation of Functionalised Particles by Finite Dilution Inverse Gas Chromatography
Vikram Karde and Jerry Y. Y. Heng, Imperial College
Surface Energy Characterisation of Functionalised Particle by Finite Dolution Inverse Gas Chromatography
Vikram Karde, Jerry Y.Y. Heng
Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Contact Email:
Abstract:
Surfaces of particulate solids govern major interparticle interactions and complete surface characterisation could provide a better understanding of their behaviour in different pharmaceutical settings and unit operations. Surface energy of solids is one of the critical property for consideration during formulation design and development as well as processing. The present work is a part of Virtual Formulation Lab (VFL) project which aims to predict and optimise the manufacturability of solid particulates by addressing the processes like powder flow, mixing, compaction and caking using suitable manufacturability indicators. This research focuses on determining the thermodynamic surface energy of crystalline powders to provide new insights into the physics of surface transformation for use in formulation design. With this aim, here we highlight the work on anisotropy and heterogeneity in crystalline materials, surface energy heterogeneity characterisation using Finite Dilution Inverse Gas Chromatography (FD-IGC) as well as the influence of processing (milling, mixing) and surface functionalisation on the energetics of crystalline materials. The characterisation work was carried out using D-Mannitol and glass beads as model materials. From the facet-specific surface energies obtained from contact angle studies on the macroscopic single crystal of D-Mannitol, we demonstrate the anisotropic nature of crystalline materials. Experiments with functionalised surfaces and milled materials rendered different trends in the surface energy heterogeneity depending on the nature of functionalisation and crystalline disorder. Also, mixing studies revealed that in the case of multi-component binary systems, surface energetics could be influenced by the mechanisms of interparticle surface interactions or structuring of the component particles. Furthermore, a Boltzmann distribution model and simulation fitting approach was developed to deconvolute the distribution of changing energy landscape of the surfaces. In conclusion, we show that FD-IGC is an effective tool to characterise the surfaces of crystalline solids and to tease out the process-induced changes in them.
Figure 1. Surface characterisation of crystalline solids
Calculation of Surface Free Energy in Mannitol Crystals through Cleaving
Nicodemo Di Pasquale, Ruslan Davidchack, University of Leicester
Calculation of Surface Free Energy in Mannitol Crystals through Cleaving
Nicodemo Di Pasquale, Ruslan L. Davidchack
Department of Mathematics, University of Leicester, University Rd, Leicester, LE1 7RH
Contact Email:
Surface Free Energy (SFE) represents an important quantity in numerous industrial applications ranging from nucleation [1] to powder flowability [2]. The calculation of this quantity through Molecular Dynamics allows to obtain the value of the SFE directly from its statistical mechanics definition. Among the different methods developed to compute this quantity, the cleaving method [3], which belongs to the wider class of Thermodynamic Integration methodologies, is one of the most precise. The method is conceptually simple: a sample of a material in a phase α and a sample of a material in a phase β are cut in two and the different halves are put in contact. The reversible work per unit area needed to perform these operations is equal to the SFE. In this study we demonstrate an extension of the cleaving method to a molecular system, the mannitol. This method proves to be reliable and relatively simple to implement when more complicated systems, such as mannitol, are considered.
Predictive Methods Powder Flow, Caking and Segregation Problems in Formulation Design
Hamid Salehi Kahrizsangi, Vivek Garg, and Mike Bradley, Greenwich University
Predictive Methods for Powder Flow, Caking and Segregation Problems in Formulation Design
Hamid Salehi, Vivek Garg, Robert Berry, Tong Deng, Richard Farnish, Mike Bradley*
Wolfson Centre for Bulk Solids Handling Technology, University of Greenwich
*Contact Email:
The main focus is to predict flow function from the particle properties using a small quantity of powder sample in order to predict any flowability problems at an early stage of formulation. Two approaches have been developed i.e. to link either the Bond number or the tensile strength with the flow function of the powder. For evaluating the first approach, a novel technique (Drop Test) was developed to measure the detachment forces between the aggregated particles. This technique is used to predict flow function from the adhesive forces using Bond Number. Another technique was developed to measure the value of tensile strength after compaction for investigating the second approach. The measured values were compared with tensile strengths obtained from the pull off forces from annular shear cell tester and using extrapolation of the yield locus from the PFT Tester. The methodology of linking the flow function with the bond number (using drop test) shows promising results.
Caking and segregation cause many problems in powder processing. Caking strength is effectively an extreme case of powder flow. A novel force-displacement and easy-to-use caking tester for measuring quantitatively cake strength from a small quantity of powder as a result of elevated temperature, consolidation stress and storage time is developed. Tester was designed to overcome some of the limitations of traditional uniaxial caking tester due to the defined location of the failure plane, to maximise repeatability, minimize production cost, exposed surface and lower wall friction. The results showed that the tester could distinguish caking strength with varying experimental conditions. Statistical model has been successfully developed to study effect of each experimental variable on the cake strength. An established segregation tester has been used to study the linkage between powder flow properties and free-surface segregation. A partial model has been developed which is under investigation.
Prediction of Flowability of Powder Mixtures at High Strain Rate Conditions by Discrete Element Method
M. Pasha, X. Jia, M. Ghadiri, University of Leeds
DigiPac/DigiDEM – Applications and Future Developments
Xiaodong Jia, Mehrdad Pasha, Mojtaba Ghadiri, University of Leeds
DigiPac/DigiDEM – Applications and Future Developments
Xiaodong Jia, Mehrdad Pasha, Mojtaba Ghadiri
School of Chemical & Process Engineering
University of Leeds, Leeds LS2 9JT, UK
Contact Email:
Packing of particles, or structure made of particulates, is ubiquitous in everyday life and in industrial applications. The packing structure is known to be dependent on shape and size distribution of particles. DigiPac is a software suite designed to perform particle-level simulation of packing of arbitrary shapes and sizes, and to subsequently calculate a range of structure-related properties including permeability, flow through porous media and particle-fluid interactions. This poster showcases some capabilities of the packing modules that may potentially be useful for simulations of behaviour of pharmaceutical powder particles, and extensible for faceted crystals and particles undergoing deformation and/or breakage.