Professor Charley Wu


Professor of Chemical Engineering
+44 (0)1483 683506
15 BC 02

Biography

Areas of specialism

Computational formulation engineering; Pharmaceutical engineering; Discrete Element Modelling; Particle Engineering and Technology

My qualifications

PhD
Aston University

Research projects

Indicators of esteem

  • Proposal Reviewer: European Research Council (ERC); National Science Foundation of China (NSFC); Natural Sciences and Engineering Research Council of Canada; The Executive Agency for Higher Education, Research, Development and Innovation, Romania; French National Research Agency (ANR); Qatar National Research Fund (QNRF).

    Member of EPSRC College (2005-)

    Guest Editor: Powder Technology, Particuology, Granular Matter, Materials.

    Editorial Board Member: Particuology, Journal of Engineering.

    PhD Examiner: The universities of Cambridge, Imperial College, Edinburgh, Southampton, Birmingham, Sheffield, Leicester, Leeds, Newcastle, Surrey and Glasgow Caledonian University in the UK; Abo Akademi University in Finland; University of New South Wales \& Monash University in Australia; University of Toulouse in France.

    Opponent for PhD thesis public defence: Abo Akademi University, Finland; Ecole Des Mines, Albi, France

    Peer Reviewer: Powder Technology, AICHE J, Chemical Engineering Science, Proceedings of the Royal Society London, International Journal of Pharmaceuticals, Journal of Pharmaceutical Science.

    Expert Consultant: In the field of X-ray Computed Tomography for pharmaceutical solid oral dosage forms.

     

My teaching

My publications

Publications

Yu S, Guo Y, Wu C-Y (2009) DEM/CFD modelling of the deposition of dilute granular systems in a vertical container, CHINESE SCIENCE BULLETIN 54 (23) pp. 4318-4326 SCIENCE PRESS
Wu CY, Li LY, Thornton C (2005) Energy dissipation during normal impact of elastic and elastic-plastic spheres, INTERNATIONAL JOURNAL OF IMPACT ENGINEERING 32 (1-4) pp. 593-604 PERGAMON-ELSEVIER SCIENCE LTD
Xing M, Wu C, Adams MJ (2011) The saltations of different sized particles in aeolian sand transport, GEOMORPHOLOGY 134 (3-4) pp. 217-223 ELSEVIER SCIENCE BV
Guo Y, Wu C-Y, Kafui KD, Thornton C (2010) Numerical analysis of density-induced segregation during die filling, POWDER TECHNOLOGY 197 (1-2) pp. 111-119 ELSEVIER SCIENCE SA
Guo Y, Wu C-Y, Thornton C (2013) Modeling Gas-Particle Two-Phase Flows with Complex and Moving Boundaries using DEM-CFD with an Immersed Boundary Method, AICHE JOURNAL 59 (4) pp. 1075-1087 WILEY-BLACKWELL
Yu S, Wu CY, Adams MJ, Reynolds G, Gururajan B, Gargiuli J, Leadbeater T, Roberts R, Parker DJ (2015) The use of positron emission particle tracking (PEPT) to study milling of roll-compacted microcystalline cellulose ribbons, Powder Technology 285 pp. 74-79
© 2015 Elsevier B.V.Milling is a critical process for controlling the properties of the granules produced by roll compaction. In the current study, the positron emission particle tracking (PEPT) technique was used to examine the milling kinematics of roll-compacted ribbons at various milling speeds. Microcrystalline cellulose (MCC, Avicel PH-102) was used as the model feed material and a radioactive particle (tracer) was mixed with the MCC powder and roll-compacted to form sample ribbons. They were then milled using an oscillating mill at various speeds and the kinematics of the ribbons (trajectory, velocity, and occupancy) were quantitatively determined using PEPT. A close examination of the PEPT data reveals that, for milling MCC PH-102 ribbons using the oscillating mill considered in this study, the milling speed plays an important role: at low values, the milling process is dominated by cooperative motion of the ribbons with the blade (i.e. the speeds of the ribbons and the blade are similar, and the ribbons move along with the blade) and the ribbons are milled primarily by abrasion; as the speed increases the ribbons undergo more random motion involving collisions that results in an increase in ribbon breakage and hence an increase in the milling efficiency. It is shown that the PEPT technique is a useful technique for examining milling kinematics of roll-compacted ribbons.
Schiano S, Wu C-Y, Mirtic A, Reynolds G (2016) A novel use of friability testing for characterising ribbon milling behaviour, EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 104 pp. 82-88 ELSEVIER SCIENCE BV
Wu C-Y, Bentham AC, Mills A (2007) Analysis of failure mechanisms during powder compaction, Progress in Powder Metallurgy, Pts 1 and 2 534-536 pp. 237-240 TRANS TECH PUBLICATIONS LTD
Guo Y, Wu CY, Thornton C (2011) The effects of air and particle density difference on segregation of powder mixtures during die filling, Chemical Engineering Science 66 (4) pp. 661-673
Segregation of mono-disperse binary mixtures with different particle densities during die filling in the presence of air was numerically analysed using a coupled discrete element method (DEM) and computational fluid dynamics (CFD) approach. Die filling with powders of different particle density ratios (i.e. the ratio of the heavy particles to the light particles) at various shoe speeds was simulated, in order to explore the effects of air and particle density difference on segregation. For die filling from a stationary shoe, the air can induce significant segregation by hindering the deposition of light particles (i.e., air-sensitive particles). As the particle density ratio increases, the light particles are deposited into the die at even lower speeds compared with the heavy ones due to the effect of air drag, resulting in an increase in the degree of segregation. For die filling with a moving shoe, segregation occurs due to different post-collisional velocities resulting from different particle inertia; and the degree of segregation increases as the particle density ratio increases due to the increasing difference in particle inertia. It is found that, as the shoe velocity increases, the powder flow pattern changes from nose flow dominated to bulk flow dominated and the degree of segregation generally decreases. The effect of air is limited for nose flow dominated die filling because the air can easily evacuate through the gap between the die walls and flowing powder stream. When bulk flow dominates in die filling, the air can be entrapped in the die, which has a significant impact on the powder flow and segregation behaviours. Finally, the effect of interparticle friction on segregation was investigated. © 2010 Elsevier Ltd.
Wu CY, Dihoru L, Cocks ACF (2003) The flow of powder into simple and stepped dies, POWDER TECHNOLOGY 134 (1-2) pp. 24-39 ELSEVIER SCIENCE SA
Patel BA, Adams MJ, Turnbull N, Bentham AC, Wu C-Y (2010) Predicting the pressure distribution during roll compaction from uniaxial compaction measurements, CHEMICAL ENGINEERING JOURNAL 164 (2-3) pp. 410-417 ELSEVIER SCIENCE SA
Wu C-Y, Guo Y, Nikoosaleh S, Thornton C (2009) Competing Flow of Dissimilar Granular Materials in Air, POWDERS AND GRAINS 2009 1145 pp. 985-988 AMER INST PHYSICS
Wu C-Y, Hancock BC, Mills A, Bentham AC, Best SM, Elliott JA (2008) Numerical and experimental investigation of capping mechanisms during pharmaceutical tablet compaction, POWDER TECHNOLOGY 181 (2) pp. 121-129 ELSEVIER SCIENCE SA
Wu CY, Thornton C, Li LY (2003) Coefficients of restitution for elastoplastic oblique impacts, ADVANCED POWDER TECHNOLOGY 14 (4) pp. 435-448 VSP BV
Pei C, Wu CY, Adams M, England D, Byard S, Berchtold H (2014) Contact electrification and charge distribution on elongated particles in a vibrating container, Chemical Engineering Science
The electrostatic charge can be transferred between particles during collisions. The particle shape plays an important role and, in the current study, the charge accumulation and distribution on elongated particles in a vibrating container are investigated using a discrete element method, in which a contact electrification model is implemented. The elongated particle geometry is modelled using a multi-sphere approach. Five different shapes are considered and characterized using a shape factor, ´, which is defined as the ratio of the difference of the radii between the distal sphere and central sphere to the mean radius of the particle. It is found that the net charge on the central sphere is greater than that on the distal sphere when ´0, greater net charge is accumulated on the larger distal sphere. The maximum surface charge difference between the distal and central sphere increases as the shape factor increases. The net charge of the granular system with different particle shapes achieves an equilibrium state during the vibrating process. This accumulating process follows an exponential trend. © 2014 Elsevier Ltd. All rights reserved.
Pei C, Wu C-Y, Adams M, England D, Byard S, Berchtold H (2013) A DEM Model for Contact Electrification of Irregular Shaped Particles, POWDERS AND GRAINS 2013 1542 pp. 101-104 AMER INST PHYSICS
Yu S, Wu C-Y, Adams MJ, Reynolds G, Gururajan B, Gargiuli J, Leadbeater T, Roberts R, Parker DJ (2015) The use of positron emission particle tracking (PEPT) to study milling of roll-compacted microcystalline cellulose ribbons, POWDER TECHNOLOGY 285 pp. 74-79 ELSEVIER SCIENCE BV
Wu CY, Cocks ACF, Gillia OT, Thompson DA (2003) Experimental and numerical investigations of powder transfer, POWDER TECHNOLOGY 138 (2-3) pp. 216-228 ELSEVIER SCIENCE SA
Nwose EN, Pei C, Wu C-Y (2012) Modelling die filling with charged particles using DEM/CFD, PARTICUOLOGY 10 (2) pp. 229-235 ELSEVIER SCIENCE INC
Wu C-Y (2013) Special issue on discrete element modelling, POWDER TECHNOLOGY 248 pp. 1-2 ELSEVIER SCIENCE BV
Coube O, Cocks ACF, Wu CY (2005) Experimental and numerical study of die filling, powder transfer and die compaction, POWDER METALLURGY 48 (1) pp. 68-76 MANEY PUBLISHING
Yu S, Gururajan B, Reynolds G, Roberts R, Adams MJ, Wu C-Y (2012) A comparative study of roll compaction of free-flowing and cohesive pharmaceutical powders, INTERNATIONAL JOURNAL OF PHARMACEUTICS 428 (1-2) pp. 39-47 ELSEVIER SCIENCE BV
Li LY, Wu CY, Thornton C (2002) A theoretical model for the contact of elastoplastic bodies, PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART C-JOURNAL OF MECHANICAL ENGINEERING SCIENCE 216 (4) UNSP C06401 pp. 421-431 PROFESSIONAL ENGINEERING PUBLISHING LTD
Roll compaction is a commonly used dry granulation process in pharmaceutical, fine chemical and agrochemical industries for materials sensitive to heat or moisture. The ribbon density distribution plays an important role in controlling properties of granules (e.g. granule size distribution, porosity and strength). Accurate characterisation of ribbon density distribution is critical in process control and quality assurance. The terahertz imaging system has a great application potential in achieving this as the terahertz radiation has the ability to penetrate most of the pharmaceutical excipients and the refractive index reflects variations in density and chemical compositions. The aim of this study is to explore whether terahertz pulse imaging is a feasible technique for quantifying ribbon density distribution. Ribbons were made of two grades of microcrystalline cellulose (MCC), Avicel PH102 and DG, using a roll compactor at various process conditions and the ribbon density variation was investigated using terahertz imaging and section methods. The density variations obtained from both methods were compared to explore the reliability and accuracy of the terahertz imaging system. An average refractive index is calculated from the refractive index values in the frequency range between 0.5 and 1.5THz. It is shown that the refractive index gradually decreases from the middle of the ribbon towards to the edges. Variations of density distribution across the width of the ribbons are also obtained using both the section method and the terahertz imaging system. It is found that the terahertz imaging results are in excellent agreement with that obtained using the section method, demonstrating that terahertz imaging is a feasible and rapid tool to characterise ribbon density distributions.
Wu C-Y, Guo Y (2012) Numerical modelling of suction filling using DEM/CFD, CHEMICAL ENGINEERING SCIENCE 73 pp. 231-238 PERGAMON-ELSEVIER SCIENCE LTD
Pei C, Wu CY, England D, Byard S, Berchtold H, Adams M (2013) Numerical analysis of contact electrification using DEM-CFD, Powder Technology 248 pp. 34-43
Contact electrification occurs in many powder handling processes and involves electrostatic charges that are transferred between contacting particles during collisions. In the current paper, a successive condenser model was developed and implemented into a discrete element method coupled with computational fluid dynamics (DEM-CFD) to analyse the charge transfer during powder processing. The numerical results for the contact electrification between a dielectric particle and a neutral conductive surface were in excellent agreement with experimental data reported in the literature. It was also shown that, during single collisions, the transferred charge is proportional to the maximum contact area but decreases linearly as the initial charge of the particle increases. In a successive impact process, charge accumulation on a particle increases exponentially with the number of collisions and eventually reaches an equilibrium state. During these processes, larger particles gain higher steady state charge but the charge-to-mass ratio is smaller. Nevertheless, particles of different sizes have identical surface charge density and charging coefficient when the impact velocity is identical. In the case of gas fluidization, the electrostatic charge gradually accumulates on particles and eventually reaches an equilibrium state. Non-uniform charge distribution is generally induced. A higher superficial gas velocity results in a faster charge accumulation due to increased collision frequency and impact velocity. © 2013 Elsevier B.V.
Wu CY, Best SM, Bentham AC, Hancock BC, Bonfield W (2005) A simple predictive model for the tensile strength of binary tablets, EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 25 (2-3) pp. 331-336 ELSEVIER SCIENCE BV
Yang J, Wu C-Y, Adams M (2013) DEM Analysis of Effects of Particle Properties and Mixing Conditions on Particle Attachment Processes, POWDERS AND GRAINS 2013 1542 pp. 967-970 AMER INST PHYSICS
Pei C, Wu C-Y, Adams M (2015) Numerical analysis of contact electrification of non-spherical particles in a rotating drum, POWDER TECHNOLOGY 285 pp. 110-122 ELSEVIER SCIENCE BV
Wu C-Y, Thornton C, Li L-Y (2008) Rebound behaviour of spheres during elastic-plastic oblique impacts, INTERNATIONAL JOURNAL OF MODERN PHYSICS B 22 (9-11) pp. 1095-1102 WORLD SCIENTIFIC PUBL CO PTE LTD
Guo Y, Kafui KD, Wu C-Y, Thornton C, Seville JPK (2009) A Coupled DEM/CFD Analysis of the Effect of Air on Powder Flow During Die Filling, AICHE JOURNAL 55 (1) pp. 49-62 JOHN WILEY & SONS INC
Wu CY, Fan XF, Motazedian F, Seville JPK, Parker DJ, Cocks ACF (2007) An experimental study of die filling using positron emission particle tracking, Proceedings of the Euro Powder Metallurgy Congress and Exhibition, Euro PM 2007 3 pp. 335-340
Positron Emission Particle Tracking (PEPT) is a non-invasive technique which enables quantitative information on the position and 3D motion of a tracer particle during processing to be determined at high frequencies. This technique has been successfully used to investigate powder behaviour during mixing, fluidization, granulation, etc. In this study, PEPT was employed to examine the flow behaviour of powders during die filling. Time histories of displacement and velocity of traced particles were determined. It has been found that the measured displacement and velocity in the moving direction of the feed shoe corresponds very well with the specified shoe motion, demonstrating that the motion of particles during die filling can be accurately determined using PEPT. This will provide useful information to fully understand the die filling process.
Wu C-Y, Poeschel T (2013) Micro-mechanics and dynamics of cohesive particle systems, GRANULAR MATTER 15 (4) pp. 389-390 SPRINGER
Qiu L-C, Wu C-Y (2014) A hybrid DEM/CFD approach for solid-liquid flows, JOURNAL OF HYDRODYNAMICS 26 (1) pp. 19-25 ELSEVIER SCIENCE INC
Wu CY, Cocks ACF (2004) Flow behaviour of powders during die filling, POWDER METALLURGY 47 (2) pp. 127-136 MANEY PUBLISHING
Wu C-Y, Seville JPK (2009) A comparative study of compaction properties of binary and bilayer tablets, POWDER TECHNOLOGY 189 (2) pp. 285-294 ELSEVIER SCIENCE SA
Guo Y, Wu CY, Kafui KD, Thornton C (2011) 3D DEM/CFD analysis of size-induced segregation during die filling, Powder Technology 206 (1-2) pp. 177-188
The flow and segregation behaviours of the binary mixtures with different particle sizes during die filling in air and in a vacuum were investigated using a coupled discrete element method (DEM) and computational fluid dynamics (CFD) in three dimensions (3D). Two types of computational setups were considered: i) a fully 3D model with real wall boundaries and ii) a thin sliced model with a slice of the full domain using two parallel periodic boundaries. Die filling with a stationary shoe and a moving shoe were simulated. It was found that the flow and segregation results obtained using the fully 3D and thin sliced models were essentially identical, implying that the thin sliced model can be used to simulate the die filling with a reduced computational time and good accuracy. It was also observed that, for die filling with a stationary shoe, the powder flow rate was reduced by the entrapped air in the die. For the die filling in a vacuum, vertical segregation occurred with a high concentration of fine particles at the bottom of the die as the fine particles can sift through the voids between coarse particles. The presence of air reduced the extent of this segregation by suppressing the percolation of fines through the voids. For die filling with a moving shoe, the effect of air on powder flow and segregation behaviours is negligible when the process is dominated by nose flow as considered in this study, since the air can readily escape from the die cavity. Segregation was also induced during die filling with a moving shoe, due to the free surface segregation and the filtration of fines through the voids between the coarse particles. Consequently, a high overall concentration of fines in the die was obtained, while the concentration of fines at the far end of the die was much lower than that at the near end. © 2010 Elsevier B.V.
Wu CY, Ruddy OM, Bentham AC, Hancock BC, Best SM, Elliott JA (2005) Modelling the mechanical behaviour of pharmaceutical powders during compaction, POWDER TECHNOLOGY 152 (1-3) pp. 107-117 ELSEVIER SCIENCE SA
Wu C-Y, Best SM, Bentham AC, Hancock BC, Bonfield W (2006) Predicting the tensile strength of compacted multi-component mixtures of pharmaceutical powders, PHARMACEUTICAL RESEARCH 23 (8) pp. 1898-1905 SPRINGER/PLENUM PUBLISHERS
Wu CY, Pöschel T (2013) Micro-mechanics and dynamics of cohesive particle systems, Granular Matter 15 (4) pp. 389-390
Wu C-Y, Ge W (2012) Special Issue on Emerging Particle Technology, POWDER TECHNOLOGY 227 pp. 1-2 ELSEVIER SCIENCE SA
Miguelez-Moran AM, Wu C-Y, Dong H, Seville JPK (2009) Characterisation of density distributions in roller-compacted ribbons using micro-indentation and X-ray micro-computed tomography, EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 72 (1) pp. 173-182 ELSEVIER SCIENCE BV
Yang J, Wu CY, Adams M (2013) DEM analysis of particle adhesion during powder mixing for dry powder inhaler formulation development, Granular Matter 15 (4) pp. 417-426
Understanding the adhesive interactions between active pharmaceutical ingredient (API) particles and carrier particles in dry powder inhalers (DPIs) is critical for the development of formulations and process design. In the current study, a discrete element method, which accounts for particle adhesion, is employed to investigate the attachment processes in DPIs. A critical velocity criterion is proposed to determine the lowest impact velocity at which two elastic autoadhesive spherical particles will rebound from each other during impact. Furthermore, the process of fine API particles adhering to a large carrier in a vibrating container is investigated. It was found that there are optimal amplitude and frequency for the vibration velocity that can maximise the number of particles contacting with the carrier (i.e. The contact number). The impact number and detachment number during the vibration process both increase with increasing vibration amplitude and frequency while the sticking efficiency decreases as the amplitude and frequency are increased. © 2013 Springer-Verlag Berlin Heidelberg.
Wu C-Y, Hung W-L, Miguelez-Moran AM, Gururajan B, Seville JPK (2010) Roller compaction of moist pharmaceutical powders, INTERNATIONAL JOURNAL OF PHARMACEUTICS 391 (1-2) pp. 90-97 ELSEVIER SCIENCE BV
Wu CY, Cocks ACF, Gillia OT (2003) Die filling and powder transfer, INTERNATIONAL JOURNAL OF POWDER METALLURGY 39 (4) pp. 51-64 AMER POWDER METALLURGY INST
Murray FJ, Hicks M, Colón J, Wu CY, Natoli D, Kirsch D, Salvemini D (2012) Optimizing manufacturing processes: conditions, challenges and opportunities, American Pharmaceutical Review 15 (3)
Pei C, Wu CY, Adams M, England D, Byard S, Berchtold H (2015) Contact electrification and charge distribution on elongated particles in a vibrating container, Chemical Engineering Science 125 pp. 238-247
© 2014 Elsevier Ltd.The electrostatic charge can be transferred between particles during collisions. The particle shape plays an important role and, in the current study, the charge accumulation and distribution on elongated particles in a vibrating container are investigated using a discrete element method, in which a contact electrification model is implemented. The elongated particle geometry is modelled using a multi-sphere approach. Five different shapes are considered and characterized using a shape factor, ´, which is defined as the ratio of the difference of the radii between the distal sphere and central sphere to the mean radius of the particle. It is found that the net charge on the central sphere is greater than that on the distal sphere when ´0, greater net charge is accumulated on the larger distal sphere. The maximum surface charge difference between the distal and central sphere increases as the shape factor increases. The net charge of the granular system with different particle shapes achieves an equilibrium state during the vibrating process. This accumulating process follows an exponential trend.
Yang J, Wu CY, Adams M (2014) Three-dimensional DEM-CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers., Acta pharmaceutica Sinica. B 4 (1) pp. 52-59
Air flow and particle-particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers (DPIs). Hence, an understanding of these mechanisms is critical for the development of DPIs. In this study, a coupled DEM-CFD (discrete element method-computational fluid dynamics) is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations. A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow. It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed. Furthermore, the influence of the air velocity and work of adhesion are also examined. It is shown that the dispersion number (i.e., the number of API particles detached from the carrier) increases with increasing air velocity, and decreases with increasing the work of adhesion, indicating that the DPI performance is controlled by the balance of the removal and adhesive forces. It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance, which is governed by the ratio of the fluid drag force to the pull-off force.
Wu CY, Li LY, Thornton C (2003) Rebound behaviour of spheres for plastic impacts, INTERNATIONAL JOURNAL OF IMPACT ENGINEERING 28 (9) pp. 929-946 PERGAMON-ELSEVIER SCIENCE LTD
Pei C, Wu C-Y, England D, Byard S, Berchtold H, Adams M (2015) DEM-CFD modeling of particle systems with long-range electrostatic interactions, AICHE JOURNAL 61 (6) pp. 1792-1803 WILEY-BLACKWELL
Wu CY (2006) Capping mechanisms during pharmaceutical powder compaction, AIChE Annual Meeting, Conference Proceedings
Pharmaceutical tablets are the most popular dosage form for drug delivery. The tablets are generally produced by compacting dry powders. During pharmaceutical powder compaction, the tablets produced need to sustain their integrity during the process and have to be strong enough to sustain any possible load experienced during the post-compaction processes, such as coating, packing and handling. Hence, any defects, such as chipping, capping and laminating, are not tolerable during pharmaceutical powder compaction. However, such defects are common problems during the tabletting process. Therefore, understanding the failure mechanisms of these defects has attracted considerable attention. In this paper, only the mechanisms of capping were considered. Previous studies on capping during pharmaceutical powder compaction have been reviewed. Capping mechanisms have been further explored by conducting a combined experimental and computational study on pharmaceutical powder compaction. An instrumented hydraulic press (also known as compaction simulator) has been used to investigate the powder behaviour during the compaction. In addition, an instrumented die has also been used, which enable the material properties to be extracted for some real pharmaceutical powders. Close attentions have been paid to the occurrence of capping during tabletting. An X-ray Computed Microtomography system has also used to examine the internal failure patterns of the tablets produced using the compactions simulator. Furthermore, pharmaceutical powder compaction has also been analysed using finite element (FE) methods, in which the powder was modelled as an elastic-plastic continuum medium following Drucker-Prager-Cap yield criteria and the material properties were determined from the uniaxial compaction with an instrumented die. In both experimental and numerical studies, cylindrical tablets with different surface curvatures, including Flat-face round tablets and convex tablets, were considered. From the experimental observation, it is clear that different capping patterns were obtained for different shaped tablets: cone-shaped capping for flat-faced tablets and normal capping with essentially horizontal failure surface for convex tablets. It was also observed in the experiments that capping takes place at the early stage of decompression (unloading), i.e., the top punch begins to withdraw. Close examination of FEA results reveals that the capping is associated with an intensive shear ban
Wu C-Y, Thornton C, Li L-Y (2009) A semi-analytical model for oblique impacts of elastoplastic spheres, PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES 465 (2103) pp. 937-960 ROYAL SOC
Miguelez-Moran AM, Wu C-Y, Seville JPK (2008) The effect of lubrication on density distributions of roller compacted ribbons, INTERNATIONAL JOURNAL OF PHARMACEUTICS 362 (1-2) pp. 52-59 ELSEVIER SCIENCE BV
Wu C-Y, Fan XF, Motazedian F, Seville JPK, Parker DJ, Cocks ACF (2010) Quantitative investigation of powder flow during die filling using positron emission particle tracking, PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART E-JOURNAL OF PROCESS MECHANICAL ENGINEERING 224 (E3) pp. 169-175 SAGE PUBLICATIONS LTD
Yang J, Wu C-Y, Adams M (2015) Numerical Modelling of Agglomeration and Deagglomeration in Dry Powder Inhalers: A Review, CURRENT PHARMACEUTICAL DESIGN 21 (40) pp. 5915-5922 BENTHAM SCIENCE PUBL LTD
Goey CH, Wu C-Y (2013) Cooperative Dynamics of a Group of Intruders Subsiding in Granular Media: a DEM Study, POWDERS AND GRAINS 2013 1542 pp. 437-440 AMER INST PHYSICS
Andrews J, Yu S, Gururajan B, Reynolds G, Roberts R, Wu C-Y, Adams M (2010) Analytical solutions for roll compaction of pharmaceutical powders, JOURNAL OF PHARMACY AND PHARMACOLOGY 62 (10) pp. 1403-1404 WILEY-BLACKWELL
Wu CY, Hancock BC, Elliott JA, Best SM, Bentham AC, Bonfield W (2005) Finite element analysis of capping mechanisms during pharmaceutical powder compaction, Advances in Powder Metallurgy and Particulate Materials - 2005, Proceedings of the 2005 International Conference on Powder Metallurgy and Particulate Materials, PowderMet 2005 pp. 62-73
In this paper, the compaction of lactose powder, a typical pharmaceutical excipient, is modelled using finite element methods (FEM) in which the powder is represented by an elastic-plastic continuum medium following Drucker-Prager Cap yield criteria. In a recent numerical and experimental study by the present authors [1], it was found that cone-shaped capping failure occurs during compaction of flat-faced round tablets, and that cone capping is associated with intensive shear band formation during the decompression stage. It is hence instructive to explore possible approaches that might alleviate the propensity for capping. Two approaches to alleviate capping were therefore investigated through finite element analysis: (i) altering the surfaces of the punches, i.e. to make convex tablets using the same material properties, and (ii) altering the material properties, i.e. changing the elasticity of the materials. It was found that capping still takes place even if the surface curvatures of the punches are altered. These predictions have been confirmed by physical experiments using a compaction simulator. The experiments have also demonstrated convincingly that the capping occurs during decompression. The second approach has been investigated in such a way that only the Young's modulus of the powder is changed to values twice and one-half that of lactose. Numerical results reveal that intensive shear bands are still developed during decompression even when the material properties are changed in this way. This implies that similar capping patterns are still possible for those materials. It is anticipated that the reason that some pharmaceutical excipients, such as microcrystalline cellulose (Avicel PH-102), do not cap is because of the high bonding strength of such materials (which can be generally characterised by tensile strength) [2].
Yu S, Adams M, Gururajan B, Reynolds G, Roberts R, Wu C-Y (2013) The effects of lubrication on rollcompaction, ribbon milling and tabletting, CHEMICAL ENGINEERING SCIENCE 86 pp. 9-18 PERGAMON-ELSEVIER SCIENCE LTD
Yang J, Wu C-Y, Adams M (2014) DEM analysis of the effect of electrostatic interaction on particle mixing for carrier-based dry powder inhaler formulations, PARTICUOLOGY 23 pp. 25-30 ELSEVIER SCIENCE INC
Wu C-Y, Ge W (2012) Special Issue Advances in Characterization and Modeling of Particulate Processes Preface, PARTICUOLOGY 10 (2) pp. 145-145 ELSEVIER SCIENCE INC
Wu C, Pei C, Byard S (2013) A DEM model for contact electrification of irregular shaped particles, AIP Conference Proceedings 1542 pp. 101-104
Understanding the adhesive interactions between active pharmaceutical ingredient (API) particles and carrier particles in dry powder inhalers (DPIs) is critical for the development of formulations and process design. In the current study, a discrete element method, which accounts for particle adhesion, is employed to investigate the attachment processes in DPIs. A critical velocity criterion is proposed to determine the lowest impact velocity at which two elastic autoadhesive spherical particles will rebound from each other during impact. Furthermore, the process of fine API particles adhering to a large carrier in a vibrating container is investigated. It was found that there are optimal amplitude and frequency for the vibration velocity that can maximise the number of particles contacting with the carrier (i.e. the contact number). The impact number and detachment number during the vibration process both increase with increasing vibration amplitude and frequency while the sticking efficiency decreases as the amplitude and frequency are increased. © 2013 Springer-Verlag Berlin Heidelberg.
Yang J, Wu C-Y, Adams M (2015) DEM analysis of the effect of particle-wall impact on the dispersion performance in carrier-based dry powder inhalers, INTERNATIONAL JOURNAL OF PHARMACEUTICS 487 (1-2) pp. 32-38 ELSEVIER SCIENCE BV
Wu C (2012) Discrete Element Modelling of Particulate Media,
Wu CY, Fan XF, Motazedian F, Seville JPK, Parker DJ, Cocks ACF (2010) Quantitative investigation of powder flow during die filling using positron emission particle tracking, Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering 224 (3) pp. 169-175
The flow behaviour of powders during die filling was investigated using the positron emission particle tracking (PEPT) technique, from which quantitative information on the flow of individual particles was obtained. Two grades of spherical microcrystalline cellulose powders with different particle sizes were used as the model powder systems. It is shown that the trajectories of tracked particles at different initial positions are consistent with the overall flow patterns observed using a high-speed video system and linear kinematics (i.e. displacement and velocity) of the tracked particles in the moving direction of the feed shoe correspond very well with the specified shoe motion. Furthermore, a close examination of the vertical velocity component (i.e. in the gravitational direction) of the tracked particles that were deposited into the die reveals that for the system with large particles, the particles flow into the die at a higher falling velocity, compared to the system with small particles. This is primarily due to the effect of the presence of air in the die, which can significantly inhibit the flow of small particles, while its effect on the flow of large particles is small.
Pei C, Adams M, Wu C-Y, England D, Byard S, Berchtold H (2013) Numerical analysis of contact electrification using DEM-CFD, Powder Technology
Contact electrification occurs in many powder handling processes and involves electrostatic charges that are transferred between contacting particles during collisions. In the current paper, a successive condenser model was developed and implemented into a discrete element method coupled with computational fluid dynamics (DEM-CFD) to analyse the charge transfer during powder processing. The numerical results for the contact electrification between a dielectric particle and a neutral conductive surface were in excellent agreement with experimental data reported in the literature. It was also shown that, during single collisions, the transferred charge is proportional to the maximum contact area but decreases linearly as the initial charge of the particle increases. In a successive impact process, charge accumulation on a particle increases exponentially with the number of collisions and eventually reaches an equilibrium state. During these processes, larger particles gain higher steady state charge but the charge-to-mass ratio is smaller. Nevertheless, particles of different sizes have identical surface charge density and charging coefficient when the impact velocity is identical. In the case of gas fluidization, the electrostatic charge gradually accumulates on particles and eventually reaches an equilibrium state. Non-uniform charge distribution is generally induced. A higher superficial gas velocity results in a faster charge accumulation due to increased collision frequency and impact velocity. © 2013 Elsevier B.V. All rights reserved.
Milroy GE, Dutt M, Wu CY, Bentham AC, Hancock BC, Elliott JA, Cameron RE (2004) The use of desktop x-ray microtomography to characterise randomly packed and compacted pharmaceutical participate systems, Transactions - 7th World Biomaterials Congress
The use of desktop X ray microtomography (XMT) to characterize randomly packed pharmacheutical particulate systems was discussed. The XMT work was performed using a 1072 Sky Scan desktop system. Glass spheres were used for the particle packing experiment with an average particle size of 200 ¼m transferred to borosilicate glass capillary tubes of 3 mm diameter. The 2D X-ray tomography images showed clearly defined spheres contained in capillary tube.
Wu C-Y, Thornton C, Li L-Y (2009) Predicting Rebound Kinematics of Elastic and Rigid Particles Resulting from Oblique Impacts, POWDERS AND GRAINS 2009 1145 pp. 755-758 AMER INST PHYSICS
Wu C-Y, Ge W, Britain RSOCG (2011) Particulate Materials Synthesis, Characterisation, Processing and Modelling, Royal Society of Chemistry
Aimed at addressing these challenges, this book contains a selection of papers discussing the state-of-the-art research in particulate materials science that were presented at the UK China Particle Technology Forum III held at Birmingham, ...
Thornton C, Ning Z, Wu CY, Nasrullah M, Li LY (2001) Contact mechanics and coefficients of restitution, GRANULAR GASES 564 pp. 184-194 SPRINGER-VERLAG BERLIN
Schiano Serena, Chen L, Wu Chuan-Yu (2017) The effect of dry granulation on flow behaviour of pharmaceutical powders during die filling, Powder Technology 337 pp. 78-83 Elsevier
Flowability that quantifies the flow behaviour of powders is an important material attribute for such applications as packing, hopper flow and powder transport. It is also one of the critical material attributes of pharmaceutical formulations for solid dosage forms. It is anticipated that size enlargement via dry/wet granulation will improve the flowability of feed powders, but it is still unclear how significant the flowability can be enhanced. Therefore, in this study, an experimental investigation was performed to explore how dry granulation affects the flowability of pharmaceutical powders, such as microcrystalline cellulose (MCCs), mannitol and lactose. Both as-received powders and binary mixtures were considered. Granules of various sizes were produced using roll compaction followed by ribbon milling, and the flowability of as-received powders and produced granules was characterised using two methods: 1) the critical filling speed measured using a model die filling system and 2) the flow index measured using a Flodex tester. It was shown that the flowability increases as the size of the granules increases for all materials considered. Furthermore, it was found that there is a strong correlation between the critical filling speed and the flow index: the critical filling speed is proportional to the flow index to a power of ? 5/2.
Wu CY, Cocks ACF (2006) Numerical and experimental investigations of the flow of powder into a confined space, MECHANICS OF MATERIALS 38 (4) pp. 304-324 ELSEVIER SCIENCE BV
Wu C-Y (2013) An Energy-based Splash Function for the Impact of Particles with Granular Beds, POWDERS AND GRAINS 2013 1542 pp. 630-633 AMER INST PHYSICS
Pei C, Wu CY, Adams M (2015) Numerical analysis of contact electrification of non-spherical particles in a rotating drum, Powder Technology 285 pp. 110-122
© 2015 Elsevier B.V..Contact electrification is generally referred to as the charge transfer process between particles during collisions. The transferred charge can be accumulated on the surface of the particles especially for insulating materials with irregular shapes, which can lead to a non-uniform charge distribution and eventually affects the charge accumulation process. In this study, in order to investigate the influence of the particle shape on contact electrification, a sphere-tree multi-sphere method and a contact electrification model are implemented into the discrete element method (DEM) to model the charging process of irregular particles in a rotating drum. Irregular particles with various Sauter mean diameters but the same maximum diameter and equivalent volume diameters are considered. The charge distribution and accumulation on the particles are investigated. It is found that the charge transfer originates from the contact between the particle and the drum due to the contact potential difference and initially takes place primarily at the region near the wall of the drum. The charge eventually propagates to the entire granular bed. The charge of the particles increases exponentially to an equilibrium value. For particles with the same maximum diameter, a larger charging coefficient is obtained for the particles with smaller Sauter mean diameters and sphericities, which leads to a faster charge accumulation, while for particles with the same equivalent volume diameter and fill ratio, similar charging coefficients are observed. A non-uniform intra-particle charge distribution is induced on each individual multi-sphere particle.
Wu C-Y (2008) DEM simulations of die filling during pharmaceutical tabletting, PARTICUOLOGY 6 (6) pp. 412-418 ELSEVIER SCIENCE INC
Wu C-Y, Michrafy A, Mendyk A, Watano S (2015) Pharmaceutical Particle Technology, POWDER TECHNOLOGY 285 pp. 1-1 ELSEVIER SCIENCE BV
Wu C-Y, Armstrong B, Vlachos N (2012) Characterization of Powder Flowability for Die Filling, PARTICULATE SCIENCE AND TECHNOLOGY 30 (4) pp. 378-389 TAYLOR & FRANCIS INC
Guo Y, Kafui KD, Thornton C, Wu CY (2007) A numerical study of die filling using a coupled discrete element method and computational fluid dynamics, Proceedings of the Euro Powder Metallurgy Congress and Exhibition, Euro PM 2007 3 pp. 317-322
In this paper, die filling from a stationary shoe in vacuum and in air was analysed using a coupled discrete element method (DEM) and computational fluid dynamics (CFD) code in which the powder is modelled using DEM while the air is analysed using CFD, and the airparticle interaction is considered. The influence of particle size and size distribution on the flow behaviour was also explored. It has been demonstrated that the coupled DEM/CFD is capable of simulating the complex interaction between the air and the powder during die filling. The numerical simulations have revealed that the presence of air during die filling has a significant impact on the powder flow behaviour, especially for the system with smaller particle sizes.
Wu C, Krok A, García-Triñanes P, Peciar, M (2016) Finite element analysis of thermomechanical behaviour of powders during tabletting., Chemical Engineering Research and Design 110 pp. 141-151 Elsevier
In the current paper, a systematic finite element (FE) analysis of the thermo-mechanical behaviour of pharmaceutical powders during die compaction is performed using the FE solver ABAQUS. The transformation of irreversible compression work to heat during compaction is considered, so is the energy dissipated by the particle-particle friction, and die-wall friction. Die compaction with various shaped punches to produce flat-face (FF), shallow convex (SC) and standard convex (STC) tablets at different compression speeds are then analysed. Evolutions of density and temperature distributions during compaction are examined. The effect of die wall friction on thermo-mechanical behaviours is also explored. It is shown that the punch shape, the compression speed and die-wall friction significantly affect the thermo-mechanical behaviour. The maximum temperature and temperature distribution of the compressed powder changes dramatically when different shaped punches are used. The maximum temperature of the tablet upon ejection can be reduced by decreasing the die-wall friction or the compression speed.
Wu C (2000) Impact behaviour of elastoplastic spheres with a rigid wall, Proc. I. Mech. E. Part C- Journal of Mechanical Engineering Science 214 (8) pp. 1107-1114
Yu S, Gururajan B, Reynolds G, Roberts R, Wu C-Y, Adams M (2010) Exploring roll compaction of two commonly used pharmaceutical powders, JOURNAL OF PHARMACY AND PHARMACOLOGY 62 (10) pp. 1434-1435 WILEY-BLACKWELL
Pei C, Wu C-Y, Byard S, England D (2010) Numerical analysis of electrostatic effects during powder deposition using DEM/CFD, JOURNAL OF PHARMACY AND PHARMACOLOGY 62 (10) pp. 1454-1455 WILEY-BLACKWELL
Wu C-Y, Guo Y (2010) Modelling of the flow of cohesive powders during pharmaceutical tabletting, JOURNAL OF PHARMACY AND PHARMACOLOGY 62 (10) pp. 1450-1451 WILEY-BLACKWELL
Lu X, Chen L, Wu C, Chan H, Freeman T (2017) Effects of relative humidity on flowability and dispersion performance of lactose mixtures, Materials 10 (6) 592 MDPI
The flowability and dispersion behavior are two important physicochemical properties of pharmaceutical formulations for dry powder inhalers (DPIs). They are usually affected by the environmental conditions, such as temperature and relative humidity (RH). However, very few studies have been focused on the relationship between the two properties and their dependence on RH during storage. In this research, model pharmaceutical formulations were prepared using mixtures of coarse and fine lactose. The fractions of fines in the mixtures were 0%, 5%, 10% and 20%, respectively. These blends were stored at four different RH, 0%, 30%, 58% and 85%, for 48 hours. The FT4 Powder Rheometer was used to evaluate the powder flowability, and the Malvern Spraytec® laser diffraction system was employed to assess the powder dispersion performance. The results indicated that both the flow and dispersion properties of lactose blends deteriorate after being stored at 85% RH, but improved after being conditioned at 58% RH. The fine particle fractions (FPFs) of the blends with 5% and 10% fine fractions and the as-received coarse lactose decreased when they were conditioned at 30% RH. For the blend with 20 % fine fraction, a high RH during storage (i.e., 85%RH) affected the dispersion property, but had a limited influence on its flowability. While, for the coarse lactose powder, the different RH conditions only affected its flowability, but not the dispersion results. A strong correlation between the powder flowability and its dispersion performance was found.
Ojha V, Schiano S, Wu C, Snasel V, Abraham A (2016) Predictive Modelling of Die Filling of the Pharmaceutical Granules Using the Flexible Neural Tree, Neural Computing and Applications 29 (7) pp. 467-481 Springer Verlag
In this work, a computational intelligence (CI) technique named flexible neural tree (FNT) was developed to predict die filling performance of pharmaceutical granules and to identify significant die filling process variables. FNT resembles feedforward neural network, which creates a tree-like structure by using genetic programming. To improve accuracy, FNT parameters were optimized by using differential evolution algorithm. The performance of the FNT-based CI model was evaluated and compared with other CI techniques: multilayer perceptron, Gaussian process regression, and reduced error pruning tree. The accuracy of the CI model was evaluated experimentally using die filling as a case study. The die filling experiments were performed using a model shoe system and three different grades of microcrystalline cellulose (MCC) powders (MCC PH 101, MCC PH 102, and MCC DG). The feed powders were roll-compacted and milled into granules. The granules were then sieved into samples of various size classes. The mass of granules deposited into the die at different shoe speeds was measured. From these experiments, a dataset consisting true density, mean diameter (d50), granule size, and shoe speed as the inputs and the deposited mass as the output was generated. Cross-validation (CV) methods such as 10FCV and 5x2FCV were applied to develop and to validate the predictive models. It was found that the FNT based CI model (in the cases of both CV methods) performed much better than other CI models. Additionally, it was observed that process variables such as the granule size and the shoe speed had a higher impact on the predictability than that of the powder property such as d50. Furthermore, validation of model prediction with experimental data showed that the die filling behavior of coarse granules could be better predicted than that of fine granules.
Loreti S, Wu C, Reynolds G, Mirti
A, Seville J
(2017) DEM-PBM Modelling Of Impact Dominated Ribbon Milling, AIChE Journal 63 (9) pp. 3692-3705 Wiley
Ribbon milling is a critical step in dry granulation using roll compaction as it determines the properties of granules, and subsequently the properties of final products. During ribbon milling, fragmentation of ribbons or flakes (i.e. compressed agglomerates from dry powders) are induced by either impact or abrasion. Understanding these fragmentation mechanisms is critical in optimising ribbon milling processes. In the current study, the discrete element method (DEM) was used to model fragmentation at the microscopic level, providing a detailed insight into the underlying breakage mechanism. In DEM modelling, virtual ribbons were created by introducing an appropriate interfacial energy using the cohesive particle model. A set of three-dimensional parallelepiped ribbons with solid fraction Æ=0.7422 and surface energies ranging from ³=0.03 JDm^2 and ³=2 JDm^2 were created and then fractured during impacts with a plane at various impact velocities, in order to model impact dominated milling. The fragmentation rate, and the number and size of fragments (i.e. granules) resulting from the breakage of a ribbon during the impact were determined. The DEM simulations showed that the granules size distribution had a bimodal pattern and there was a strong correlation between the size of fines generated from fragmentation during impact and the size of the feed powder (i.e. the size of the primary particles in this study), which was consistent with the observation from physical experiments. Two quantities were calculated from the DEM simulations: the number of fragments p and the fraction of fines z for each breakage event which can be used as input parameters for population balance models (PBM) to develop a DEM-PBM modelling framework.
As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely
used to deliver active drugs into the human body, satisfying patient?s therapeutic requirements.
To manufacture tablets of good quality, diluent powders are generally used in formulation
development to increase the bulk of formulations and to bind other inactive ingredients with the active
pharmaceutical ingredients (APIs). For formulations of a low API dose, the drug products generally
consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely
important and can significantly influence the final product property. Therefore, it is essential to
accurately characterise the mechanical properties of the diluents and to thoroughly understand how
their mechanical properties affect the manufacturing performance and properties of the final products,
which will build a sound scientific basis for formulation design and product development. In this
study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical
diluent powders, including microcrystalline cellulose (MCC) powders with different grades (i.e.,
Avicel PH 101, Avicel PH 102, and DG), mannitol SD 100, lactose monohydrate, and dibasic calcium
phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita
analyses. The material elastic recovery during decompression and in storage was investigated
through monitoring the change in the dimensions of the compressed tablets over time. The powder
hygroscopicity was also evaluated to examine the water absorption ability of powders from the
surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after
ejection, which is believed to be induced by (1) water absorption from the surrounding, and (2) elastic
recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed
by the material shrinkage in storage. It is anticipated that the expansion was induced by elastic
recovery to a limited extent, while the shrinkage was primarily due to the solidification during
storage. It was also found that, for all powders considered, the powder compressibility and the
elastic recovery depended significantly on the particle breakage tendency: a decrease in the particle
breakage tendency led to a slight decrease in the powder compressibility and a significant drop in
immediate elastic recovery. This implies that the particle breakage tendency is a critical material
attribute in controlling the compression behaviour of pharmaceutical powders.
Radjai F, Stavrou A, Hare C, Hassanpour A, Wu C, Nezamabadi S, Luding S, Delenne J (2017) Flowability assessment of weakly consolidated powders, EPJ Web of Conferences 140 pp. 03085-1-03085-4 EDP Sciences: EPJ Open Access
The inability of cohesive powders to flow consistently and reliably is a major cause of process downtime and reduced efficiency across a wide range of powder processing industries. Most methods to assess powder flowability fail at low consolidation pressures (
Loreti Simone, Wu Chuan-Yu, Reynolds G, Seville Jonathan (2017) DEM-PBM modelling of abrasion dominated ribbon breakage, AIChE Journal 64 (4) pp. 1191-1204 JOHN WILEY & SONS INC
In dry granulation, fine cohesive powders are compacted into large multi-particle entities, i.e., briquettes, flakes or ribbons. The powder compaction is generally followed by milling, a size reduction process, which is crucial to obtain the desired granule size or properties. Abrasion and impact are two primary mechanisms of comminution in ribbon milling, but they are not completely understood. The aim of this paper was hence to investigate numerically the fragmentation process induced by abrasion during ribbon milling. The discrete element method (DEM) was employed to simulate abrasion tests, for which three-dimensional parallelepiped ribbons were generated using auto-adhesive elastic spheres. The fragmentation rate, and the fragments size and number were determined for various surface energies and abrasive velocities. The DEM results showed that the mass-equivalent fragment size distributions were bi-modal, similar to the experimental observations and the numerical results for impact-dominated ribbon milling reported in the literature. In addition, two quantities were determined from the DEM analysis, i.e. the number of large fragments and the fraction of fines, which was then integrated into the population balance models (PBM) so that a DEM-PBM multiscale modelling framework was developed to predict the granule size distribution during ribbon milling. The DEM-PBM results were compared with the experimental results reported in the literature, and a broad agreement was obtained, implying the proposed DEM-PBM can be used to analyse the ribbon milling behaviour.
Krok A, Vitorino N, Zhang Jianyi, Ribeiro Frade J, Wu Chuan-Yu (2017) Thermal properties of compacted pharmaceutical excipients, International Journal of Pharmaceutics 534 (1-2) pp. 119-127 Elsevier
Thermal properties of powders are critical material attributes that control temperature rise during tableting and roll compaction. In this study, various analytical methods were used to measure the thermal properties of widely used pharmaceutical excipients including microcrystalline cellulose (MCC) of three different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and mannitol. The effect of relative density on the measured thermal properties was investigated by compressing the powders into specimen of different relative densities. Differential thermal analysis (DTA) was employed to explore endothermic or exothermic events in the temperature range endured during typical pharmaceutical manufacturing processes, such as tabletting and roll compaction. Thermogravimetric analysis (TGA) was performed to analyse the water/solvent content, either in the form as solvates or as loosely bound molecules on the particle surface. Thermal conductivity analysis (TCA) was conducted to measure thermal conductivity and volumetric heat capacity. It is shown that, for the MCC powders, almost no changes in morphology or structural changes were observed during heating to temperatures up to 200 °C. An increase in relative density or temperature leads to a high thermal conductivity and the volumetric heat capacity. Among all MCC powders considered, Avicel DG showed the highest increase in thermal conductivity and the volumetric heat capacity, but this heat capacity was not sensitive to the measurement temperature. For lactose and mannitol, some endothermic events occurred during heating. The thermal conductivity increased with the increase in temperature and relative density. A model was also developed to describe the variation of the thermal conductivity and the volumetric heat capacity with the relative density and the temperature. It was shown that the empirical model can well predict the dependency of the thermal conductivity and the volumetric heat capacity on the relative density and the temperature.
Zhang Jianyi, Wu Chuan-Yu, Storey David, Byrne Gerard (2017) The interfacial strength of bilayer pharmaceutical TABLETs, Powder Technology Elsevier
The oral drug delivery system using bilayer (or multilayer) tablets has become more commonly used in therapeutic strategies. However, one of the most common problems associated with bilayer tablets is the insufficient interfacial strength between layers, which leads to product failure during manufacturing. Therefore, it is important to better understand the interfacial strength of bilayer pharmaceutical tablets. For this purpose, in this study, the interfacial strength of bilayer tablets made of microcrystalline cellulose (MCC PH 102) at various manufacturing conditions was systematically examined. Three cases were considered: (1) the effect of interfacial curvature on the interfacial strength, for which the interfaces between two layers with different curvatures were produced using flat, convex and concave punches. (2) The effect of water content on the interfacial strength, for which the powder was conditioned at various relative humidity before being used to produce bilayer tablets. (3) The effect of the particle size of the powder used in first layer on the interfacial strength, for which the feed powder was sieved to obtain powders with specific particle sizes that were then used to produce the first layer of the bilayer tablets. For all cases considered, direct tensile tests were performed to measure the tablet interfacial strength. It is found that the interfacial curvature, the water content and the particle size in the first layer affected the interfacial strength significantly. It is also shown that the tablet interfacial strength was increased when larger particles were used in the first layer, or when curved punches (i.e. either convex or concave punches) were used to produce curved interfaces with increased interfacial areas. In addition, a higher interfacial strength can also be achieved by properly controlling water content in the powder.
Understanding the dependence of the strength of agglomerates on material properties, interfacial properties and structure of the agglomerate is critical in many processes involving agglomerates. For example, in the manufacturing of pharmaceutical tablets and pellets with dry granulation, understanding the relationship between the ribbon properties and the properties of the granules is critical in controlling the granulation behaviour, and the ribbon properties (e.g. tensile strength and density distribution) is determined by the material properties of the feed powders, interfacial properties between particles and the process condition, which determine the structure of the ribbons. This study aims to investigate the effect of the surface energy and porosity on the bending strength of pharmaceutical ribbons, for which three-dimensional discrete element modelling with a cohesive particle model based upon the JKR theory was performed. Simulations were carried out using specimens of various porosities and surface energies. The dependence of the bending strength on the surface energy and the ribbon porosity was examined. It was found that there is a strong correlation between the bending strength with porosity and surface energy. In particular, the bending strength is proportional to the surface energy and is an exponential function of the porosity.
Cai J, Wu Charley, Guo Y, Yang J, Zhao X (2018) Mechanistic Analysis of Solid-liquid Flow during Injection, Particuology Elsevier
Direct injection of retinal cells into the eyes of patients is a new and better therapeutic method for cataract, but the challenge is that the survival rate of cells during injection is very low. In order to solve this problem, in this study, the force distribution of retinal cells in the injectors with two needle shapes was analysed using coupled discrete element method with computational fluid dynamics (DEM-CFD), in which an immersed boundary method was implemented. Two injectors were considered: one with a straight needle and the other with a curved needle. It was found that the velocities of retinal cells in the injector with a straight needle were slightly higher than that with a curved needle. In addition, the injection speed greatly affected the force distribution of retinal cells, and the retinal cells near the piston were subjected to the highest forces during injection. It was also found that the forces on retinal cells increased as the concentration of the cells increase, and the forces of retinal cells increased evidently with the increasing of piston displacement.
Govender Nicolin, Wilke D, Wu Charley, Khinast J, Pizette P, Xu W (2018) Hopper flow of irregularly shaped particles (non-convex polyhedra):
GPU-based DEM simulation and experimental validation,
Chemical Engineering Science 188 pp. 34-51 Elsevier
Numerous practical applications of the Discrete Element Method (DEM) require a flexible description of particles
that can account for irregular and non-convex particle shape features. Capturing the particle non-convexity is
important since it allows to model the physical interlocking when the particles are in contact. To that end, the
most flexible approach to capture the particle shape is via a polyhedron, which provides a faceted representation of
any shape, albeit at a significant computational cost. In this study we present a decomposition approach to modeling
non-convex polyhedral particles as an extension of an existing open source convex polyhedral discrete element code,
BlazeDEM-GPU, which computes using general purpose graphical processing units (GPGPUs). Although the
principle of decomposition of non-convex particles into convex particles is not new, its application by the discrete
element modeling community has been rather limited. The non-convex extension of BlazeDEM-GPU was validated
using a hopper flow experiment with identical convex and identical non-convex 3D printed particles. The experiment
was designed around two sensitive flow points, with the convex particles following the intermittent flow and the nonconvex
particles forming stable arches. It was demonstrated that the DEM simulations can be applied to reproduce
both the convex and the non-convex flow behavior using the same parameter set. This study is a significant step
towards general computing of non-convex particles for industrial-scale applications using the GPGPUs.
The oral drug delivery system using bilayer tablets has become more commonly used in therapeutic strategies as it has several advantages over conventional single layer tablets such as the modified drug release, physical separation of chemically incompatible therapeutics, elongation of product patent life, etc. However, one of the common problems associated with bilayer tablets is the insufficient interfacial strength between layers, which may lead to product failure during the manufacturing process. Therefore, it is important to gain a good understanding on bilayer technology to bring bilayer design and manufacturing to similar levels of robustness as encountered in single layer tablets.
In this thesis, the attributes (e.g. compressibility, elasticity, compactibility and hygroscopicity) of the commonly used pharmaceutical powders were firstly investigated to thoroughly understand how these mechanical properties affect the manufacturing performance and product quality, which built a sound scientific basis for formulation design. Based on the material property investigation, a plastic powder (MCC PH 102) and a brittle material (mannitol SD 100) were selected to produce bilayer tablets. The interfacial strength of these tablets was evaluate using two different methods: direct tensile test and terahertz pulsed imaging system. The tablet interfacial strength was used in the analysis to investigate the impacts of the different factors on tablet integrity. For instance, the influences of both powder conditions (e.g. powder formulation, mean particle size and water content) and manufacturing process conditions (e.g. compression pressure, dwell time and punch geometry) on bilayer tablet interfacial strength were examined. In addition, the elastic contact theory was also used to model the particulate contacts at the bilayer tablet interface.
Govender Nicolin, Wilke Daniel, Wu Chuan-Yu, Rajamani Raj, Khinast Johannes, Glasser Benjamin J. (2018) Large-scale GPU based DEM modeling of mixing using irregularly shaped particles, Advanced Powder Technology 29 (10) pp. 2476-2490 Elsevier
Mixing of particulate systems is an important process to achieve uniformity, in particular pharmaceutical processes that requires the same amount of active ingredient per tablet. Several mixing processes exist, this study is concerned with mechanical mixing of crystalline particles using a four-blade mixer. Although numerical investigations of mixing using four-blades have been conducted, the simplification of particle shape to spherical or rounded superquadric particle systems is universal across these studies. Consequently. we quantify the effect of particle shape, that include round shapes and sharp edged polyhedral shapes, on the mixing kinematics (Lacey Mixing Index bounded by 0 and 1) that include radial and axial mixing as well as the inter-particle force chain network in a numerical study. We consider six 100 000 particles systems that include spheres, cubes, scaled hexagonal prism, bilunabirotunda, truncated tetrahedra, and a mixed particle system. This is in addition to two six million particle systems consisting of sphere and truncated tetrahedra particles that we can simulate within a realistic time frame due to GPU computing. We found that spherical particles mixed the fastest with Lacey mixing indices of up to 0.9, while polyhedral shaped particle systems mixing indexes varied between 0.65 and 0.87, for the same mixing times. In general, to obtain a similar mixing index (of 0.7), polyhedral shaped particle systems needed to be mixed for 50% longer than a spherical particle system which is concerning given the predominant use of spherical particles in mixing studies.
Xue Jun, Schiano Serena, Zhong Wenzhen, Chen Lan, Wu Chuan Yu (2018) Determination of the flow/no-flow transition from a flat bottom hopper, Powder Technology Elsevier
Hoppers and silos are widely used in storing powders in various industries, such as agricultural, chemical, food and pharmaceutical industries. It is of practical importance to design hoppers and silos to ensure smooth discharge of bulk solids from these devices, and to minimise the occurrence of arching, blockage and build-up of materials around the walls. However, due to the complex nature of bulk solids, arching behaviour of bulk solids in silos and hoppers is still not well understood. In this study, a combined experimental and numerical study was performed to explore the transition from non-flow to flow of bulk solids from a flat bottom hopper. Glass beads of various sizes were considered and the minimal orifice size through which these materials can be discharged was determined experimentally using a FlodexTM
Zawbaa Hossam M., Schiano Serena, Perez-Gandarillas Lucia, Grosan Crina, Michrafy A, Wu Charley (2018) Computational Intelligence Modelling of Pharmaceutical Tabletting Processes Using Bio-inspired Optimization Algorithms, Advanced Powder Technology 29 (12) pp. 2966-2977 Elsevier
In pharmaceutical development, it is very useful to exploit the knowledge
of the causal relationship between product quality and critical material at-
tributes (CMA) in developing new formulations and products, and optimizing
manufacturing processes. With the big data captured in the pharmaceutical
industry, computational intelligence (CI) models could potentially be used
to identify critical quality attributes (CQA), CMA and critical process pa-
rameters (CPP). The objective of this study was to develop computational
intelligence models for pharmaceutical tabletting processes, for which bio-
inspired feature selection algorithms were developed and implemented for
optimisation while artificial neural network (ANN) was employed to pre-dict the tablet characteristics such as porosity and tensile strength. Various
pharmaceutical excipients (MCC PH 101, MCC PH 102, MCC DG, Mannitol
Pearlitol 200SD, Lactose, and binary mixtures) were considered. Granules
were also produced with dry granulation using roll compaction. The feed
powders and granules were then compressed at various compression pres-
sures to produce tablets with different porosities, and the corresponding ten-
sile strengths were measured. For the CI modelling, the efficiency of seven
bio-inspired optimization algorithms were explored: grey wolf optimization
(GWO), bat optimization (BAT), cuckoo search (CS),
ower pollination al-
gorithm (FPA), genetic algorithm (GA), particle swarm optimization (PSO),
and social spider optimization (SSO). Two-thirds of the experimental dataset
was randomly chosen as the training set, and the remaining was used to val-
idate the model prediction. The model efficiency was evaluated in terms of
the average reduction (representing the fraction of selected input variables)
and the mean square error (MSE).It was found that the CI models can well
predict the tablet characteristics (i.e. porosity and tensile strength). It was
also shown that the GWO algorithm was the most accurate in predicting
porosity. While the most accurate prediction for the tensile strength was
achieved using the SSO algorithm. In terms of the average reduction, the GA algorithm resulted in the highest reduction of inputs (i.e. 60%) for pre-
dicting both the porosity and the tensile strength.
Zakhvatayeva A., Zhong W., Makroo H.A., Hare C., Wu C. (2018) An experimental study of die filling of pharmaceutical powders using a rotary die filling system, International Journal of Pharmaceutics 553 (1-2) pp. 84-96 Elsevier
Die filling is a critical process step in pharmaceutical tablet manufacturing. Mass and content uniformity of the tablets as well as production throughput depend upon the die filling performance of the formulations. The efficiency of the die filling process is influenced by powder properties, such as flowability, cohesion, particle size and morphology, as well as the process conditions. It is hence important to understand the influence of powder properties on the die filling performance. The purpose of the present study is to identify the critical material attributes that determine the efficiency of die filling. For this purpose, a model rotary die filling system was developed to mimic the die filling process in a typical rotary tablet press. The system consists of a round die table of 500/mm diameter, equipped with a rectangular die. The die table can rotate at an equivalent translational velocity of up to 1.5/m/s. The filling occurs when the die passes through a stationary shoe positioned above the die table. Using this system, die filling behaviours of 7 commonly used pharmaceutical excipients with various material characteristics (e.g. particle size distribution, sphericity and morphology) and flow properties were examined. The efficiency of die filling is evaluated using the concept of critical filling velocity. It was found that the critical filling velocity is strongly dependent on such properties as cohesion, flowability, average particle size and air sensitivity index. In particular, the critical filling velocity increases proportionally as the mean particle size, flow function, air permeability and air sensitivity index increase, while it decreases with the increase of specific energy and cohesion.
Mori Yuki, Wu Chuan-Yu, Sakai Mikio (2019) Validation study on a scaling law model of the DEM in industrial gas-solid flows, Powder Technology 343 pp. 101-112 Elsevier
Large-scale gas-solid flow systems, e.g., fluidized beds, cyclone separators and pneumatic conveyors, are often encountered in chemical engineering. Numerical modeling technologies are widely applied for design and understanding of complex phenomena in these gas-solid flow systems, for which the coupled model of the discrete element method (DEM) and computational fluid dynamics is generally employed. However, application of the numerical simulations for these systems is still limited because the number of the particles that can be modeled (about several hundreds of thousand) is quite small comparing with the immeasurable number of particles used in the industrial processes, and not sufficient to fully understand the complex behavior in these processes. The coarse graining DEM is then developed to provide an alternative approach for modeling the real industrial processes. Accuracy of the coarse graining DEM has been proven for simple systems so far. In the present study, applicability of the coarse graining DEM for complex shaped domains is explored, for which typical industrial processes, such as fluidization with inserted tubes, and powder flow into a confined space, are considered. In these calculations, signed distance functions (SDF) and immersed boundary method (IBM) are used to model an arbitrary shape wall boundary in a gas-solid flow. Both numerical modeling using the coarse graining DEM and experimental investigation are performed with a thorough comparison between the experimental and numerical results. It is demonstrated that the coarse graining DEM is capable of accurately modeling of industrial gas-solid two-phase systems. Besides, this numerical approach is shown to provide valuable information such as pressure profile during powder injection and interaction between bubbles and structures in a fluidized bed.
Govender Nicolin, Wilke Daniel N., Wu Chuan-Yu, Tuzun Ugur, Kureck Hermann (2019) A numerical investigation on the effect of angular particle shapes on blast furnace burden formation using a GPU enhanced discrete element method, Chemical Engineering Science Elsevier
In blast furnaces, burden topography and packing density affect the stability of the burden, permeability of
gas flow as well as the heat transfer efficiency. A fundamental understanding of the influence and interaction
of coke and ore particles on the burden topography and packing density is therefore essential, in particular the
influence of particle shape polydispersity and particle size polydispersity. In this paper we analyze the effect
of particle shape and size polydispersity on the coke and ore charge distribution inside a bell-less blast furnace
using the discrete element method (DEM). We first validate experimentally the polyhedral particle model with a
simplified lab-scale charging experiment. A comparative study between spheres, with rolling friction to account
for shape, and polyhedra is conducted for shape and size polydisperse particle systems. It was found that
shape polydispersity mainly influenced the topography of the burden, whereas the size polydispersity mainly
influenced the inter-layer percolation, i.e. localized particle diffusion, hence the local spatial packing density.
The differences between the spherical particle models and polyhedral particle models on the burden topography
are also quantitatively and qualitatively presented, especially on the role of particle shape on the push-up of coke
in the centre. This study demonstrates that modelling particle shape effects using spheres with rolling friction is
insufficient to fully describe the complex behaviour of shaped particles in a blast furnace, as the particle shape
has a noteworthy influence on the burden characteristics.
In this study a hybrid numerical framework for modelling solid-liquid multiphase flow is established with a single-relaxation-time lattice Boltzmann method and the discrete element method implemented with the Hertz contact theory. The numerical framework is then employed to systematically explore the effect of particle concentration on the inertial migration of neutrally buoyant particle suspensions in planar Poiseuille flow. The results show that the influence of particle concentration on the migration is primarily determined by the characteristic channel Reynolds number Re0. For relatively low Re0 (Re0Â20), the migration behaviour can only be observed at a very low particle concentration (d5%). However, when Re0Ã20 the migration behaviour can be observed at a high concentration (e20%). Furthermore, a focusing number Fc is proposed to characterise the degree of inertial migration. It was found that the inertial migration can be classified into three regimes depending on two critical values of the focusing number, Fc+ and Fc-: i) when FcÃFc+, a full inertial migration occurs; ii) when FcÂFc-, particles are laterally unfocused; iii) when Fc-ÂFcÂFc+, a partially inertial migration takes place.
El Hebieshy Joesry Fouad (2019) Die filling of aerated powders.,

Die filling is a critical process step in many industries. The majority of powders or powder mixtures utilised in these industries are fine powders. Powder properties dictate the die filling rate. Die filling may cause segregation in a powder blend, which can, for example, have the detrimental effect of changing the concentration of an API in a medicinal tablet.

Using a wide range of powders, the effect of die size and die orifice shape, were investigated, as well as die orientation and aspect ratio of non-axis symmetrical dies. Passive and active die filling were compared, and the effect of varying shoe length during active die filling was also studied. Hopper flow and die filling were modelled using physical equations. The predictions of these equations were compared to the Beverloo Equations. Furthermore, size and density induced segregation of binary powder mixtures during die filling was studied.

The mass flow rate of the small die was lower than the large die even when normalised by die orifice surface area due to the trapped air dampening the flow rate more for orifices with small surface area. Higher critical filling speeds were achieved with all powders when using broad non-axis symmetrical dies in the parallel orientation. For die filling in a rotary die filling system, an empirical correlation for the prediction of the weight in the die at a given shoe speed and the critical filling speeds of any powder was developed. For hopper flow and passive die filling, physical equations were developed that were able to predict the mass flow rate of a wide range of powder more accurately than the Beverloo Equation. Finally, two segregation mechanisms were identified (sieving segregation and fluidization segregation) to occur during die filling and the speed of the shoe affected the balance between the two mechanisms.

Zakhvatayeva Anastasiya, Hare Colin, Wu Chuan-Yu (2019) Suction filling of pharmaceutical powders, Powder Technology Elsevier
Die filling is an important process step in manufacturing of
tablets. An important mechanism in the die filling process is suction
that is developed with the downward motion of the bottom punch once the
die is covered by powder. However, the contribution of suction to the die
filling performance is still poorly understood. Hence, the present study
aimed to experimentally investigate the flow behaviour of powders during
suction filling. Four different types of pharmaceutical powders were used
and a model suction filling system was developed. Effects of filling and
suction velocities, as well as powder properties, on the efficiency of
die filling were systematically investigated. Cohesive and free-flowing
powders behaved differently at various filling-to-suction velocity
ratios. The filling behaviour of cohesive powders was improved at high
filling-to-suction ratios due to acceleration-induced densification.
Free-flowing powders performed better at low filling-to suction ratios.