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Tablets are the most common solid dosage form of pharmaceutical active ingredients due to their ease of use. Their dissolution behaviour depends on the particle size distribution and physicochemical properties of the formulation, and the compression process, which need to be optimised for producing consistently robust tablets, as weaker tablets are often prone to breakage during production, transport and end use. Tablet strength is typically determined by diametric compression and friability tests. The former gives rise to propagation of a crack on a plane along the compression axis, whilst the latter, carried out in a rotating drum, incurs surface damage and produces chips and debris. These tests produce different measures of strength, neither of which have been correlated with mechanical properties that are accountable for breakage, i.e. hardness, elastic modulus and fracture toughness. We propose a new method based on single tablet impact testing, following the work of Ghadiri and Zhang (2002), who analysed particle damage by propagation of sub-surface lateral cracks and identified the fundamental form accountable for impact surface damage to be a lumped parameter related to hardness and fracture toughness. Microindentation, carried out separately, to determine fracture toughness led to complete failure of the tablets, hence an unreliable measurement of fracture toughness and no correlation with the experimental trend. In addition, by assuming the fracture toughness to be proportional to the square root of Young’s modulus, the indentation measurements do not correlate well with the impact breakage. The discrepancy between the impact and indentation methods is expected to be due to mechanical property variation across the tablet surface, and with strain rate. The impact method is a more suitable test to describe tablet propensity for attrition as it directly represents the failure mode tablets may experience during processing under well-defined conditions. In contrast, the friability test subjects tablets to a similar breakage mechanism but under less well-defined conditions, whilst the compression test represents a different failure mode that is not representative of stresses incurred during processing.
The paper entitled “Analysis of the Dynamics of the FT4 Powder Rheometer” contains calculation errors that lead to an underestimate of deviatoric stresses by a factor of ten and average compressive stresses by a factor of approximately three. The trends remain unchanged from those shown in the paper, with compressive stress and deviatoric stress both increasing approximately linearly with blade penetration depth. Here, the corrected values of compressive and deviatoric stress are given.
Coating of particulate solids by a thin film layer is of interest in many industrial applications such as seed and tablet coating. In seed processing, seeds are commonly coated with a protective coating layer consisting of fertilisers and disease control agents, such as pesticides and fungicides. Batch coaters are commonly used for this purpose. A typical coater consists of a vertical axis cylindrical vessel with a rotating base and a spray disc in the centre, onto which the coating liquid is fed to atomise and spray-coat the seeds. The seeds are driven around the vessel by its rotating base, and are mixed by two baffles; one on either side of the vessel. In the present study, Distinct Element Method (DEM) simulations are used to model the seed coating process. Corn seed are used as a model material and their shape is captured using X-Ray Tomography (XRT), which is approximated in the DEM by clumped spheres. The coating uniformity of the seeds is predicted by implementing a coating model in the DEM, whereby the coating droplets are simulated as very fine spheres projecting tangentially from a ring at the edge of the spinning disk. The size and velocity of droplets leaving the spray disk are measured using high speed video imaging and implemented into DEM simulations. The coating mechanism is represented in the DEM by considering that once a droplet contacts a corn seed, it is removed from the simulation and its mass is attributed to the coating of the corn seed. The distribution of mass of sprayed spheres on the corn seeds and their coefficient of variation are evaluated for a range of process conditions, such as the base rotational speed, atomiser disc position relative to the base and baffle arrangement and designs. It is found that the atomiser disc vertical position, baffle angle and clearance to the wall are most influential, whilst the base rotational speed and baffle width and curvature have only minimal effect.
The characterisation of bulk behaviour of cohesive powders is very important in processing of particulate solids, e.g. for reliable powder flow out of storage vessels. For filling and dosing of small quantities of powders in capsules and for dispersion in dry powder inhalers, the interest is on the behaviour of loosely-compacted powders in small quantities and under very low applied loads. Furthermore at the early stages of drug development, the quantity of the powder available is often very small and the traditional bulk testing methods are neither possible nor applicable. In this work we evaluate a method to infer powder flowability by ball indentation. This technique provides a measure of flow resistance which can be related to the unconfined yield stress. It can be applied at very low loads and requires only a small sample quantity, typically a few mm3 . The operational window in the ball indentation method in terms of minimum sample size, penetration depth and indenter properties (such as size, shape, friction and Young’s modulus) has been analysed and reported here.
Poor and inconsistent flow of cohesive powders is a major issue in powder processing. A common solution is to coat the surfaces of the cohesive particles with finer particles, referred to as flow-aids. Such particles adhere to sticky surfaces and act as spacers preventing them from contacting each other and thus reducing the inter-particle forces and bulk powder cohesion. A question which naturally arises is how much flow-aid is needed to enhance the flowability to an optimum level. This work aims to establish a relationship between the degree of Surface Area Coverage (SAC) of flow-aids and the flowability, the latter as determined by a quasi-static shear cell method, as well as the angle of repose test and the FT4 powder rheometer. Glass beads of 90-150 μm sieve cut are made cohesive by silanising their surfaces with a commercial chemical reagent, Sigmacote® and are used as host particles. Two types of zeolite particles are used as flow aids. The mass fraction of the flow aids required to achieve a theoretical SAC of 1, 5, 10, 20, 50 and 100% is first estimated and then the host particles are coated in a pan mixer. The SAC is measured by Scanning Electron Microscopy, coupled with image analysis, and found to correlate well with the estimated value. The optimum surface coverage is found to be when SAC is 10-20%, as this provides the greatest flowability. An increase in SAC beyond this range leads to a gradual reduction in flowability.
Fine cohesive powders are often dry granulated to improve their flowability. Roller compaction is commonly used to produce dense ribbons which are then milled. The material properties of the powder and the conditions in the roller compactor affect the strength of the ribbons, however there is no method in the literature to predict the size distribution of the product of ribbon milling. Here we introduce a method, by using the Distinct Element Method (DEM) to determine the prevailing impact velocities and stresses in the mill, with bonded spheres representing the ribbons. The bond strength is calibrated by matching experimental results of three point bend measurements and predictions from numerical simulations. The ribbons are then exposed to the dynamic conditions predicted by the DEM, by dropping them from a controlled height to cause fragmentation, and subsequently stressing them in a shear cell under the conditions again predicted by the DEM. The fragments are sheared under these conditions to represent repeated passage of bars over the fragments at the mill base. Sieve analysis is used here to determine the particle size distribution under given mill conditions. The predicted size distribution of the mill product compares well with the plant data. It is found that the mill speed and length of ribbons fed to the mill have no significant influence on the product size distribution for the range tested.
Auto-granulation is the growth of particle clusters within a dry, fine powder bed due to the bulk powder cohesion. This clustering occurs without the addition of any binder to the system due to simple agitation of a powder, such as during storage or handling. For this reason, it is important in powder processing to be able to characterize this behavior. In this study, a sub-micron titania powder is mechanically vibrated under controlled conditions to induce clustering and promote auto-granulation. The amplitude and frequency of the vibration is varied to view the effect on the equilibrium granule size. A statistical model of the effect is also developed to determine that the granule size increases linearly with vibrational energy. Furthermore, imaging of cross-sections of the granules is conducted to provide insight into to the internal microstructure and measure the packing fraction of the constituent particles. It is found that under all vibrational conditions investigated the particles exhibit a core-rim microstructure.
In the seed processing industry, rotary batch seed coaters are widely used for providing a protective coating layer (consisting of various ingredients including fertilisers and crop protection chemicals) on the seeds. Seed motion and mixing are important in ensuring uniform coating. In the batch seed coater, the base of a cylindrical vessel rotates, whilst the cylindrical wall is stationary and two baffles turn the bed over for mixing. In the present study, the Discrete Element Method (DEM) is used to simulate the effect of particle shape on motion and mixing in this device. Corn seed is used as a model material and the effect of its shape on motion is analysed by considering two approaches: (1) manipulation of rolling friction to account for shape as it is commonly used in the field; (2) approximation of the actual shape by a number of overlapping spheres of various sizes. The geometry of corn seeds is captured using X-Ray micro tomography and then the ASG2013 software (Cogency, South Africa) is used to generate and optimise the arrangement of the overlapping spheres. A comparison is made of the predicted tangential and radial velocity distributions of the particles from DEM and those measured experimentally. It is concluded that for rapid shearing systems with short collisional contacts a small number of clumped spheres suffices to provide a reasonable agreement with experimental results. Equally well, manipulating the rolling friction coefficient can provide results that match experiments but its most suitable value is unknown a priori, hence the approach is empirical rather than predictive.
Particles are frequently exposed to shear stresses during manufacturing, which leads to breakage. This is particularly relevant to weak active pharmaceutical ingredients and is prevalent in pharmaceutical and food industries. The attrition of Paracetamol and Aspirin caused by shear deformation at very low stresses is investigated here. The extent of breakage of these particles is related to the prevailing shear stresses and strains. In contrast to the expected trend, smaller particles exhibited increased breakage rates. At the onset of shearing at low stresses Aspirin particles experienced slightly more breakage than the Paracetamol, however prolonged shearing resulted in greater breakage of Paracetamol. Breakage occurred initially through chipping with some fragmentation, particularly more noticeable for Aspirin, with an increase in abrasion after extensive shear strain for Paracetamol. Empirical breakage relationships are proposed and when combined with process stresses and strain analyses the extent of breakage occurring in process equipment can be estimated.
In the shear deformation of powder beds beyond the quasi-static regime the shear stress is dependent on the strain rate. Extensive work has been reported on the rapid chute flow of large granules but the intermediate regime has not been widely addressed particularly in the case of cohesive powders. However in industrial powder processes the powder flow is often in the intermediate regime. In the present work an attempt is made to investigate the sensitivity of the stresses in an assembly of cohesive spherical particles to the strain rate in ball indentation using the Distinct Element Method. This technique has recently been proposed as a quick and easy way to assess the flowability of cohesive powders. It is shown that the hardness, deviatoric and hydrostatic stresses within a bed, subjected to ball indentation on its free surface, are dependent on the indentation strain rate. These stresses are almost constant up to a dimensionless strain rate of unity, consistent with trends from traditional methods of shear cell testing, though fluctuations begin to increase from a dimensionless strain rate of 0.5. For dimensionless strain rates greater than unity, these stresses increase, with the increase in hardness being the most substantial. These trends correlate well with those established in the literature for the Couette device. However quantitative value of the strain rate boundaries of the regimes differ, due to differences in the geometry of shear deformation band. Nevertheless, this shows the capability of the indentation technique in capturing the dynamics of cohesive powder flow.
Measurement of the adhesive force is of great interest in a large number of applications, such as powder coating and processing of cohesive powders. Established measurement methods such as Atomic Force Microscopy (AFM) and the centrifugal method are costly and time consuming. For engineering applications there is a need to develop a quick test method. The drop test method has been designed and developed for this purpose. In this test method particles that are adhered to a substrate are mounted on and are subjected to a tensile force by impacting the stub against a stopper ring by dropping it from a set height. From the balance of the detachment force and adhesive force for a critical particles size, above which particles are detached and below which they remain on the substrate, the interfacial specific energy is calculated. A model of adhesion is required to estimate the adhesive force between the particles and the surface, and in this work we use the JKR theory. The detachment force is estimated by Newton’s second law of motion, using an estimated particle mass, based on its size and density and calculated particle acceleration. A number of materials such as silanised glass beads, Avicel, α-lactose monohydrate and starch have been tested and the adhesive force and energy between the particle and the substrate surface have been quantified. Consistent values of the interface energy with a narrow error band are obtained, independent of the impact velocity. As the latter is varied, different particle sizes detach; nevertheless similar values of the interface energy are obtained, an indication that the technique is robust, as it is in fact based on microscopic observations of many particles. The trends of the results obtained with the drop test method are similar to those shown in studies by other researchers using established methods like the AFM and the centrifuge method.
During agitated drying and mixing processes, particle beds are exposed to shear deformation. This leads to particle attrition, the extent of which is dependent on the prevailing stresses and strains in the bed. The distributions of shear stresses and strain rates within the bed are highly non-uniform, requiring attention to localised conditions. Therefore a narrow angular sector of the bed is divided radially and vertically into a number of measurement cells, within which the stresses and strain rates are calculated throughout one rotation by the Distinct Element Method. These are then used in an empirical relationship of material breakage to predict the extent of attrition due to agitation. Here we investigate the influence of the measurement cell size on the estimated stresses and strain rates, and the subsequent effect on the predicted attrition. The measurement cell size is altered by varying the measurement sector size and the number of radial and vertical divisions within it. The median particle size is also varied to establish its influence on the predicted attrition. An increase in the average number of particles in a given cell, by varying the particle size or measurement cell dimensions, leads to a reduction in the estimated stresses and strain rates, and therefore a reduction in the predicted attrition. Comparison of the predicted attrition with the experimental breakage in the agitated vessel shows that the prediction method is accurate when the cell dimensions are comparable to the width of a naturally occurring shear band.
The Freeman FT4 Powder Rheometer has been reported to describe well the powder flow behaviour in instances where other techniques fail. We use DEM to simulate the FT4 operation for slightly cohesive large glass beads at a range of strain rates. The curved impeller is shown to be beneficial in comparison to a flat blade as the variation of shear stress across the blade is reduced. The shear stress in front of the blade correlates well with flow energy (which the device measures) for a range of tip speeds and is shown to increase approximately linearly with tip speed when operating beyond the quasi-static regime.
Spiral jet milling is a size reduction process driven by the fluid energy of high velocity gas jets. Inter-particle and particle-wall interactions are responsible for size reduction. The process is energy intensive, but inefficient. The underlying mechanisms for size reduction in the mill are also not very well understood. The optimum grinding conditions are still currently found by trial and error experimentation. In this work, the Discrete Element Method coupled with Computational Fluid Dynamics is used to investigate the effects of different parameters on the particle collisional behaviour in a spiral jet mill. These include the particle concentration in the grinding chamber, the particle size, and the fluid power input. We report on our work analysing the efficiency of energy transfer and how it can be improved by changing the milling conditions and particle properties.
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 (<1 kPa). In this paper, the ball indentation technique is used to assess the flow behaviour of two powders at low stresses by determining the bed hardness. In parallel, the powders are subjected to shear testing in a range of high stresses, with the derived unconfined yield strength used, along with the indentation hardness to define the constraint factor (C). By using the latter, which is considered independent of the preconsolidation stress applied, the unconfined yield strength of the powders at low stresses are inferred from the penetration hardness measurements.
Page Owner: ch0051
Page Created: Friday 26 February 2016 14:45:54 by mex058
Last Modified: Thursday 22 September 2016 16:57:19 by ch0051
Expiry Date: Friday 26 May 2017 14:42:51
Assembly date: Thu Jan 18 00:48:29 GMT 2018
Content ID: 160917