Grant: Predictive formulation of high-solid-content complex dispersions
PIs: Dr Jin Sun, University of Edinburgh & Dr Mark Haw, University of Strathclyde

• Paper. Establishing principles for formulation and processing of high-solid-content dispersions of complex compositions in complex flows.  Dr Jin Sun, University of Edinburgh. High-solid-content dispersions of solid particles of size about 1-50 microns in a liquid phase (HSCDs) occur ubiquitously in industrial applications, from cement and ceramic pastes to catalyst washcoats, paints, foods and drilling fluids. The reliable and efficient processing and manufacture of these diverse products presents 'grand challenges' to formulation technology because at high solids volume fraction process flow and product behaviour become increasingly unstable and unpredictable.

  In this project, using both experimental and computational studies, we have been making advances in understanding the rheology of HSCDs with industry-relevant particle properties and compositions, linking rheology to flows in non-rheometric geometries and using flow to control the dispersion rheology. Specifically, we identified the roles of particle repulsive and attractive forces, and variable particle friction in shear thickening and thinning; enhanced the understanding and the predictability of the unstable flow behaviour through analytical models and statistical analysis of oscillations in shear rates and fluctuations of local probes; tested and extended a theoretical model for shear thickening in bi-dispersed mixtures of different particle sizes or friction; established a constraint-based model that predicts all known classes of experimental flow curve; linked shear thickening rheology to liquid migration in extrusion flows and to thickening in squeezing flows; and finally were able to tune the suspension viscosity by imposing oscillatory shear onto the main flows.
  Overall, the progress provides new methodology of characterization, measurement, prediction and control of HSCD flows. The outcomes will enable manufacturers to formulate their products according to rational design principles, using parameters deduced from well-characterised reproducible flow measurements.

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• Poster. Tuning the interactions in non-model suspensions. Lewis Mchale, University of Edinburgh. Granular suspensions are widespread in multiple industries however the unification of multiple non-Newtonian affects such as shear thickening and shear thinning is not well understood. Here we use the mean field constraint theory to understand non-model silica which can be tuned between multiple rheologies using surfactant. Novel techniques allow us find that heterogeneous surface chemistry leads to unexpected rheologies and so a produced an understanding of this system from the atomic, particle and macroscopic scales.

Grant: Virtual Formulation Laboratory for prediction and optimisation of manufacturability of advanced solids based formulations
PI: Dr Csaba Sinka, University of Leicester

• Paper. 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. University of Leicester. Virtual Formulation Laboratory (VFL) is a software tool for prediction and optimisation of manufacturability and stability of advanced solids-based formulations. Four processes are considered: powder flow, mixing, compaction and storage. VFL predicts manufacturability problems quantified by suitable manufacturability indicators and accounts for a range of material types, particle structures and blend systems to enable the formulator to test the effects of formulation changes in virtual space and check for potential problems covering manufacturing difficulties experienced in production plants. In this overview the science base for understanding of surfaces, particulate structures and bulk behaviour to address physical, chemical and mechanical stability during processing and storage is introduced. The manufacturability indicators are predicted from bulk properties which are linked to particle properties and molecular information. Demonstration case studies are presented for the four manufacturing processes and problems. The talk will be followed by a more detailed presentation of the VFL approach to powder compaction.

Grant: Evaporative Drying of Droplets and the Formation of Micro-structured and Functional Particles and Film
PI: Professor Colin Bain, Durham University

• Paper. Evaporative Drying of Droplets and the Formation of Micro-structured and Functional Particles and Films. Professor Andrew Bayly- University of Leeds. 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.
• Poster. Wetting and drying of aqueous droplets with non-ionic surfactants CnEm. Jing Shi, Lisong Yang, Colin Bain - University of Durham.
• Poster. Single droplet drying kinetics and particle formation fromaerocolloidal suspension microdroplets. J. Archer*, J. S. Walker, F. K. A. Gregson, D. A. Hardy and J. P. Reid.  University of Bristol. Industrial processes such as spray drying of pharmaceutical and food products often involve the drying of aerosol droplets containing colloidal suspensions into powdered microparticles of desired properties. The morphology and surface properties of the final dry products/microparticles obtained after the drying process are strongly influenced by the parameters of the initial aerosol droplet composition and the drying conditions. In particular, the final dry microparticle morphology can be dependent on the dimensionless Péclet number (Pe), which express the relative competition between the diffusion of the dispersed particles within the droplet and the rate of solvent loss via evaporation. In this work, we examine how control over the gas phase drying conditions and initial aerosol droplet composition can be used to influence the aerosol droplet drying kinetics in the gas phase for a range of Péclet numbers. We demonstrate that, for aerosol droplets with initially low feed colloid concentrations and within the constant evaporation regime, the starting composition does not strongly influence the solvent evaporation rate with the initial included nanoparticles (NPs) acting as spectators. However, the gas phase drying conditions, temperature, and relative humidity, directly influence the droplet drying kinetics and the final dry microparticle properties. With a priori knowledge of the droplet drying kinetics from the single droplet measurements, we further demonstrate the possibility of tailoring the morphology of the dried microparticles. Our results extend the fundamental understanding of the mechanisms controlling the drying of aerosol droplets in colloidal suspensions mostly encountered in spray drying applications in the gas phase.

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

• Paper. Enabling rapid liquid and freeze-dried formulation design for the manufacture and delivery of novel biopharmaceuticals. Prof Paul Darby, University College London. Protein stability is a critical factor for the successful development of non-aggregating biopharmaceuticals and enzymes. Routes to predictably engineer protein stability are therefore crucial. We have combined a wide range of biophysical analyses, protein engineering, formulation screening, and molecular modelling approaches, to characterise some of the many factors that influence protein aggregation.  The increased understanding gained is now also being used to develop improved protein engineering and formulation design strategies for the minimisation of aggregation in liquid and freeze-dried forms.
• Poster. Supercharging proteins with small polyvalent anions offset aggregation. Jordan W. Bye, Kiah Murray and Robin A. Curtis

Grant: Complex ORAL health products (CORAL): Characterisation, modelling and manufacturing challenges
PI: Professor Panagiota Angeli, University College London

• Paper. CORAL -Viscoelastic effects during processing of complex fluids. Panagiota Angeli*, Tom Lacassagne*, Giovanni Meridiano*, Stavroula Balabani, Luca Mazzei University College London. We will present an overview of recent developments relevant to the manufacturing of complex fluid formulations. In particular we will focus on two aspects.
  We will first discuss the flows of polymer solutions in a Taylor-Couette device, an ideal geometry yet relevant to viscometric properties of the complex fluids. It is found that fluid elasticity promotes elasto-inertial chaos, whereas shear thinning delays or suppresses it - inducing a "Newtonian like" behaviour. This may have important consequences on mixing of such fluids. Neutrally buoyant particles are then suspended in the polymeric liquids, and the combined effects of particles and non-Newtonian solvent properties on the flow transitions are investigated.
  We will further present developments on the mixing of solid particles in viscoelastic fluids in a stirred vessel. A combination of laser based technique have been used to measure the velocity fields of the solid and fluid phases simultaneously along with the distribution of the solids in the tank. The experimental data show that in a Newtonian fluid particles disperse uniformly in the vessel, while in a viscoelastic fluid they tend to accumulate in the core of the vortices formed in the flow domain. The clustering, which affects the quality of the mixing, has been attributed to the viscoelasticity-induced cross-flow migration phenomenon and is linked to the viscoelastic property of the fluid.

Grant: Formulation for 3D printing: Creating a plug and play platform for a disruptive UK industry
PI: Professor Ricky Wildman, University of Nottingham

• Paper.  Formulation for 3D printing.  Prof Ricky Wildman, University of Notttingham. We will show how we can tackle materials synthesis, formulation and selection in a systematic way such that we can create libraries of materials with known functionalities ready for use in a range of industrial sectors. A number of different levers to being able to control function will be illustrated. This will include varying the geometry, the material, the distribution of material and the microstructure. I will also show how we can describe the development of properties computational such that we can create a design tool that will inform both the composition and the curing strategy that should be employed to achieve the outcome that we desire.
• Poster. A 3D printed polymeric drug-eluting implant.  Athina Liaskoni, University of Nottingham. Conventional drug delivery systems, tablets, capsules and solutions can be limited for the treatment of some diseases.  Their necessary frequent administration can be unpleasant to patients and their compliance can be reduced. Implants, and personalized implants in particular can offer a solution and 3D printing is a novel method of manufacture of such systems.  This study aims to investigate the 3D printing of persinalisable lidocaine loaded polycaprolactone implants using an extrusion-based 3D printer.  In this approach, patients will only need one drug delivery systems which will contain the exact dosages of the active ingredients they need.       During the printing, different settings have been applied for the fabrication of the drug loaded polymeric implants following optimisation for the used materials.  Physical and chemicial characterisation before and after 3D printing were carried out to investigate potential changes in material peroperties.  The drug release rate of teh differently printed formulations has been evaluated.        It has been shown that the manufacture of drug loaded polycaprolactone implants using a solvent-free method, without the addition of any excipients and at relatively low printing temperature with an extrusion-based 3D printer is feasible.  Therefore, this 3D printing method represents a promising technology for the production of personalisable drug-eluting implants.
• Poster. Formulation for 3D printing: Creating a plug and play platform for a disruptive UK industry.  Marica Malenica, University of Nottingham.

Grant: INFORM 2020 - Molecules to Manufacture: Processing and Formulation Engineering of Inhalable Nanoaggregates and Microparticles
PI: Professor Darragh Murnane, University of Hertfordshire

• Paper. INFORM 2020: Deconstructing the Role of Powder Agglomerates in Inhaled Powders. Professor Darragh Murnane, University of Hertfordshire. The state of aggregation of the active pharmaceutical ingredients (APIs) and excipients within inhaled formulations has long been known to direct the success of powder processing as well as product performance. The challenges posed for successful formulation development and manufacture are significant. Small quantities of high surface energy, micron-sized particles have a disproportionate influence on powder behaviour. Material processing frequently induces solid state and formulation instabilities which render reproducible manufacture and aerosolization performance difficult to achieve. INFORM 2020 has sought to address the challenges of inhalation formulations by developing predictive models of formulation behaviour, manufacturing processes and aerosolization events through a variety of crystal, particle, and powder modelling approaches informed by emerging, analytical techniques that probe surface and powder microstructure.
• Poster. On measuring the specific surface area of inhalation-grade lactose powders. Dr Ioanni Danal Styliari,  University of Hertfordshire
• Poster. Experimental and numerical analysis of the flow properties of different lactose grades. Xizhong Chen, University of Cambridge
• Poster. A digital approach from crystallographic structure to particle attributes for predicting the formulation properties of inhalation pharmaceuticals. Hien Nguyen, University of Leeds
• Poster. Molecular modelling metered dose inhaler suspension formulations. Vivian Walter Barron, University of Leeds
• Poster. X-ray microscopy for inhalation formulations. Parmesh Gajjar, University of Manchester. The advent of x-ray optics has allowed higher resolution and improved contrast on laboratory x-ray computed tomography machines. In particular, this has allowed us to examine the microstructure of (dry powder) inhalation formulations in the INFORM2020 project. This poster presents a summary of work including characterisation of carrier lactose, intra-agglomerate quantitative analysis for micronised lactose and examination of drug-carrier blends.