Simulation of the effect of bond strength on the breakage pattern of agglomerates by Distinct Element Method

Chemical, pharmaceutical and food industries amongst many others use agglomerates either as intermediate or manufactured products. The mechanical strength of agglomerates under impact or shear deformation during handling and processing is of great interest to these industries for optimising product specification and functionality. The effect of surface energy on agglomerate behaviour under impact has been investigated using Distinct Element Method (DEM). Four different agglomerates were formed and impacted against a target along the direction of gravity for three different values of the surface energy (0.35, 3.5 and 35.0 J/m²). The agglomerate breakage pattern was influenced by the surface energy and a transition in the mode of failure of agglomerates was observed when the surface energy was varied. Based on the previous work, the surface energy is expressed in terms of Weber Number, We=(V-V0²)ρD/γ. Agglomerates showed extensive deformation under impact at the lowest value of surface energy (0.35 J/m²) and no evidence of fragmentation was found for any value of impact velocity. In this case the agglomerates behaved macroscopically in a ductile mode. At values of surface energy larger than 3.5 J/m² the agglomerates fragmented at the same time as local damage around the impact site occurred. This type of behaviour is typical of semi-brittle material failure. Therefore, the breakage pattern of agglomerates is influenced by the surface energy

Analysis of the flowability of cohesive powders using Distinct Element Method

Computer simulations using Distinct Element Method (DEM) have been carried out to investigate the effect of cohesion on the flowability of polydisperse particulate systems. For this purpose, two assemblies with different values of surface energy and made of 3000 spheres with the mechanical properties of glass beads were considered. The analysis of the flowability of the powders is presented in terms of the unconfined yield stress as a function of strain rate for different pre-consolidation loads. For values of the surface energy of 1.0 J/m2 and strain rates lower than 6 s− 1, the unconfined yield stress does not change significantly indicating a quasi-static behaviour of the particulate assemblies during the compression process. For larger strain rates, the unconfined yield stress varies with the power index of 1.2 of the strain rate. The influence of the pre-consolidating stress on the powder behaviour has also been investigated and a flow factor was obtained from the linear relationship between the unconfined yield stress and pre-consolidation stress. The computer simulations show qualitatively a good agreement with the experimental trends on highly cohesive powder flow behaviour

Analysis of the effect of cohesion and gravity on the bulk behaviour of powders using Discrete Element Method

Computer simulations using Distinct Element Method have been carried out to analyse the bulk behaviour of a polydisperse assembly of glass beads. For this purpose an assembly made of 3000 spheres were generated to which the mechanical properties of glass beads were assigned. The system was initially compressed isotropically at a strain rate of 1 s-1 in the absence of gravity and surface energy. Once the assembly reached a packing fraction of about 0.62, the effects of cohesion and gravity on the bulk behaviour were analysed for two different cases. In the first case only gravity was applied, whilst in the second case both gravity and surface energy were acting on the particles. The evolution of the components of the stress tensor for the case in which only gravity was applied indicated that the gravity did not appreciably affect the isotropy of the system. In contrast, the system in which surface energy was introduced became anisotropic. The concept of unconfined yield stress of bulk cohesive powders was used to analyse the effect of surface energy and strain rate. For values of surface energy of 1.0 J/m2 and of strain rate lower than 1 s-1 the unconfined yield strength did not change significantly indicating a quasi-static behaviour for the compression process. However, for values of strain rates larger than 1 s-1 the unconfined yield strength increased with the strain rate, following a power law trend with an index of 1.7

Mechanistic analysis and computer simulation of impact breakage of agglomerates: Effect of surface energy

Agglomerates are ubiquitous as intermediate or manufactured products in chemical, pharmaceutical and food industries. During handling and processing they may suffer breakage if they are weak. On the other hand, if they are too strong, their dispersion and disintegration could be difficult. The control of their mechanical strength is therefore highly desirable. However, the analysis of agglomerate strength is complex due to the large number of parameters that influence agglomerate behaviour, such as the primary particle size, density and elastic modulus, and the interparticle bond strength. A simple mechanistic model is presented here which relates the number of broken contacts in agglomerate due to impact velocity, interparticle adhesion energy and the particle properties of the particles forming the agglomerate. The model is based on the hypothesis that the energy used to break contacts during impact is proportional to the incident kinetic energy of the agglomerate. The damage ratio defined as the ratio of broken contacts to the initial number of bonds is shown to depend on the dimensionless group, Δ, in the form (ρV2D5/3E2/3)/ Γ5/3, where V is the impact velocity, E the elastic modulus, D the particle diameter, ρ the particle density and Γ the interface energy. This dimensionless group, Δ, incorporates the Weber number, (ρDV2/Γ), which was previously shown to be influential in agglomerate breakage, and may be presented in the form, Δ=WeIe2/3 , where Ie = ED/ Γ. The predicted dependency of the damage ratio on the surface energy has been tested using Distinct Element Method (DEM). Four different agglomerates have been formed and impacted against a target for three different values of the surface energy of the primary particles. The simulation results show that the effect of surface energy is better described by the above mechanistic model than by the Weber number alone, as previously used to characterise the impact strength of agglomerates

3D printed agglomerates for granule breakage tests

In the research into agglomeration, a long term barrier is the lack of a universally accepted method to evaluate the breakage propensity of agglomerates. Computer simulation is often used but is limited by the lack of identical, controlled agglomerates to test and validate simple models, let alone replicate the complex structure of real industrial agglomerates. This paper presents work on the characterisation of strength of model test agglomerates prepared by a 3D printing production method enabling fully reproducible structures. Agglomerates were designed using Solidworks 2014 software and printed by an Objet500 Connex 3D printer. Materials with different mechanical properties were used to print the particles and the inter particle bonds, allowing a series of combinations of bond strength, particle strength and agglomerate structure to be tested. Compression and impact tests were performed to investigate the breakage behaviour of the printed agglomerates in terms of agglomerate orientations, bond properties and strain rates. This method will allow more rigorous testing of agglomerate breakage models

A computational drug repositioning method applied to rare diseases : adrenocortical carcinoma

Rare or orphan diseases affect only small populations, thereby limiting the economic incentive for the drug development process, often resulting in a lack of progress towards treatment. Drug repositioning is a promising approach in these cases, due to its low cost. In this approach, one attempts to identify new purposes for existing drugs that have already been developed and approved for use. By applying the process of drug repositioning to identify novel treatments for rare diseases, we can overcome the lack of economic incentives and make concrete progress towards new therapies. Adrenocortical Carcinoma (ACC) is a rare disease with no practical and definitive therapeutic approach. We apply Heter-LP, a new method of drug repositioning, to suggest novel therapeutic avenues for ACC. Our analysis identifies innovative putative drug-disease, drug-target, and disease-target relationships for ACC, which include Cosyntropin (drug) and DHCR7, IGF1R, MC1R, MAP3K3, TOP2A (protein targets). When results are analyzed using all available information, a number of novel predicted associations related to ACC appear to be valid according to current knowledge. We expect the predicted relations will be useful for drug repositioning in ACC since the resulting ranked lists of drugs and protein targets can be used to expedite the necessary clinical processes

The Effects of Ibuprofen Cytoxic Dose on caspase-3, -8 and -9 Activity level in cervical cancer (Hela) cells

BACKGROUND AND OBJECTIVE: Studies have shown that ibuprofen can have an anti-cancer effect on cervical cells, although the mechanism of this effect is not well known in cellular and molecular terms. Accordingly, the aim of this study was to investigate the effect of cytotoxic concentration of ibuprofen on the activity of caspases -3, -8 and -9 in cervical cancer (Hela) cells. METHODS: In this experimental-laboratory study, Hela cells were prepared from Pasteur Institute cell Bank and were divided into the control group and groups exposed to 0.01, 0.1, 1 and 10 mg/ml of Ibuprofen. Viability of cells was measured by MTT assay. The activity level of caspases-3, -8 and -9 was assessed by colorimetric method. The data were statistically analyzed using ANOVA. FINDINGS: The viability decreased significantly in cervical cancer cells exposed to 0.1 (76%), 1(64%) and 10(15%) mg/ml of ibuprofen compared to control group (100%)(p<0.05, p<0.001 and p<0.001 respectively). The caspases-3، -8 and -9 activity level increased significantly in cervical cancer cells exposed to IC50 dose of ibuprofen compared with control group (p<0.001, p<0.001 and p<0.01 respectively). CONCLUSION: The results of present study showed that ibuprofen is able to reduce the viability of cervical cancer cells in a dose-dependent pathway, and this pathway is induced by activating of caspases-3, -8 and -9

Analysis of screw feeding of faceted particles by discrete element method

Reliable and consistent powder flow in screw feeders is of great interest to a wide range of industries, particularly for continuous manufacturing of pharmaceutical powders. However, analysis of flow of cohesive powders with sharp corners and edges, as commonly found in the case of crystalline solids, presents a great challenge due to complexity of shape and its influence on flow. In the present work, the influence of particle shape and cohesion on phenomena such as cohesive arching in hoppers and screw feeder pitches is analysed by numerical simulations using the Discrete Element Method, and their impact on the outlet mass flow rate is evaluated. Faceted and spherical particles with different cohesion levels are generated and allowed to settle in a hopper on top of a screw feeder. The screw is then rotated, thus feeding the particles through the barrel. Particle interactions are analysed numerically for the hopper region, a predominantly slow-flow regime, and for the pitches of the screw feeder, where a speed-dependent regime prevails. Paracetamol crystal shape is taken as a model faceted shape. Its parameters such as the coefficients of restitution and friction, needed for the simulations, are calibrated by experimental work. Transient arching occurs as the level of cohesion is increased. The frequency of formation and collapse of arches within the hopper region increases, and eventually, permanent arching is observed. Analysis of stress and strain rate in the screw barrel region shows that the shear stress is a weak function of the shear rate with a power index of around 0.3, which is independent of particle shape. The flow rate is influenced considerably by particle shape, whilst increased cohesion causes an increase in void fraction and affects transient arching

DEM analysis of the effect of particle shape, cohesion and strain rate on powder rheometry

Discrete Element Method (DEM) is used to simulate the flow of particles addressing the influence of shear strain rate, particle shape and cohesion on the flow characteristics. For this purpose, the dynamics of particle motion in the Freeman Technology FT4 rheometer is analysed. The simulations are first validated by comparison with experiments with cohesive particles, i.e. silanised glass beads, from the literature. Particles with faceted shapes, sharp corners and edges are then simulated and found to require significantly higher energy to flow compared to spherical particles. The presence of truncated vertices, typical of active pharmaceutical ingredients, influences the flow behaviour drastically. The results of this analysis therefore reveal the importance of considering the actual particle shape in DEM simulations when faceted particles are considered. Finally, a rheological model describing the relationship between the dimensionless shear stress and the inertial number for several particle shapes, cohesion values and blade tip speeds is proposed. The outcome of this study may lead to a unified rheological description of powder flow, which incorporates the effect of cohesion, shape and shear strain rate