A study on the sensitivity of Drucker-Prager Cap model parameters during the decompression phase of powder compaction simulations

The compaction of pharmaceutical powders can be simulated using phenomenological elasto-plastic continuum models adopted from soil mechanics. These models are typically implemented in finite element codes and have been used recently to investigate the macroscopic property distributions in powders during compaction.The present study demonstrates the importance of obtaining accurate yield surface parameters for use in such models. A commercial finite element code implementing the Drucker-Prager Cap (DPC) model was used to model the compression and decompression stages of powder compaction in a tabletting operation. The parameters used in the DPC model were obtained from the literature. Although the compression stage of the process gave expected behavior, the decompression response was unrealistic for at least one set of published data. Small values for the friction and cohesion parameters resulted in a significant elastic recovery during decompression. This study demonstrates the need to obtain accurate parameter data in order to model the decompression stage of powder compaction.     

The effect of processing parameters on pharmaceutical tablet properties

The preferred drug delivery system today is represented by tablets, which are manufactured using high speed rotary presses where the powder material is compressed in a die between rigid punches. Compression represents one of the most important unit operations because the shape, strength and other important properties of the tablets are determined at this time. These properties are dictated not only by the characteristics of the powder constituents (which are determined by the properties of the constituents, mixing and granulation), but also by the selection of process parameters imposed by production machinery. This paper focuses on the die fill and the compaction parameters.Die fill on high speed rotary tablet production presses is a complex phenomenon. On most presses the powder is deposited into the die under the effect of the gravity. Die fill is facilitated by the paddle wheels operating in the feed frame and the suction effect, whereby the lower punch is withdrawn while the die opening is exposed to powder in the feed frame. An experimental shoe-die system was developed to examine the effect of the contributing factors. High speed video observations enabled a detailed examination of the die fill process. The flowability of powders was quantified using the concept of critical velocity. It was illustrated that a detailed understanding of die fill could contribute to the design of feed frames as well as optimisation of press parameters in order to ensure consistent and efficient die fill, thus maximising the productivity of the presses.The compaction parameters are discussed with reference to tablet strength. Results generated using a compaction simulator as well as a number of rotary tablet presses are presented for a range of pharmaceutical excipients and placebo formulations.As a result of combined interactions between the material behaviour during compaction, powder-die wall friction and process parameters during die fill and compaction, the resulting tablets are in general non-homogeneous. X-ray computed tomography is employed to characterise the internal density distribution in tablets. The effect of tablet structure on friability, erosion and disintegration behaviour is examined.     

Analysis of pharmaceutical powder compaction using multiplicative hyperelasto-plastic theory

Single-ended compaction of lactose powder is investigated numerically within the framework of multiplicative hyperelasto-plastic theory. In keeping with previous work in the pharmaceutical field, a slightly modified Drucker-Prager Cap model is described and used in the simulations. Coulomb friction is included on all interfaces. Our results indicate that simulations of this type may be useful not only to determine density and stress distributions within tablets, as has been done hitherto, but also may provide indications of circumstances under which the tableting operation fails due to capping.     

A comparative study of compaction properties of binary and bilayer tablets

Bi-layer tablets have been developed to achieve controlled delivery of different drugs with pre-defined release profiles. However, the production of such tablets has been facing great difficulties as the layered tablets are prone to fracture. In this paper, the compaction behaviour of binary mixtures and bilayer tablets of two common pharmaceutical excipients, Microcrystalline cellulose and lactose, is investigated. The effects of compositions and compaction pressure on the compaction behaviour of binary matrix mixtures and bilayer tablets are also explored. The delamination phenomena during the manufacturing of bilayer tablets and fracture patterns of tablets subjected to diametrical compression are examined using X-ray computed tomography. The mechanical properties of binary and bilayer tablets of the same composition were also determined and compared. It has been shown that for binary and bilayer tablets with the same composition, the apparent crush strength of these binary and bilayer tablets measured from diametrical compression tests were generally comparable for the powders considered in this study. It was also found that, using the same compaction process, the relative densities of the tablets were generally different when different compositions were used, especially when the maximum compression pressure is relatively low.     

Uniaxial compaction behaviour and elasticity of cohesive powders

The compression and compaction behaviour of bentonite, limestone and microcrystalline cellulose (MCC) — three cohesive powders widely used in industry were studied. Uniaxial compression was performed in a cylindrical die, 40 mm in diameter and 70 mm high, for three selected cohesive powder samples. The initial density, instantaneous density and tablet density were determined. The influence of maximum pressure and deformation rate was examined. The secant modulus of elasticity E_sec was calculated as a function of deformation rate v, maximum pressure p and powder sample. After compaction experiments in hydraulic press at three pressures - p = 30, 45 and 60 MPa - and two different deformation rates, the strength of the produced tablets was examined in a material strength testing machine.From uniaxial compression tests performed on the universal testing machine for loading and unloading, the modulus of elasticity E was calculated on the basis of the first linear phase of unloading. The total elastic recovery of tablets was also obtained.     

Wall friction in the compaction of pharmaceutical powders: measurement and effect on the density distribution

In this paper, the axial density profile of tablets of microcrystalline cellulose (MCC) powder compacted in nonlubricated die is investigated by finite element modelling (FEM). The Drucker-Prager/Cap model was adopted for the compaction behavior of powder. The material parameters of the model, including the die wall friction coefficient, were estimated from experimental data of die compaction where the initial density of powder is taken uniform. Changes of Young's modulus with density was measured with a four-point beam bending test. The results of the simulation of the compression and the decompression steps were used to calculate the axial density distribution. Comparison with the measured data presented in [A. Michrafy, M.S. Kadiri, J.A.D. Dodds, Wall friction and its effects on the density distri-bution in the compaction of pharmaceutical excipients, Chem. Eng. Research and Design, Vol. 81, Part A, September (2003)] is discussed.     

Experimental calibration of density-dependent modified Drucker-Prager/Cap model using an instrumented cubic die for powder compact

Theory and experimental calibration of density dependent modified Drucker-Prager/Cap (DPC) model are presented by using a novel instrumented cubic die in powder compaction tests. The cubic die is designed for directly determining the loading and unloading forces and displacements of powder compact inside the die in compaction and transverse directions without any additional calibration. The cap surface parameters and elastic properties are characterized by fitting stress and strain curves recorded during loading and unloading at different green density values and the plastic material parameters for failure surface are obtained by additional radial and axial compressive tests. The experimental data is subsequently used in the simulation of cubic die compaction to verify the results from the density dependent modified DPC model.     

The intrinsic nature and the coherence of compacted pure pharmaceutical tablets

The paper describes methods to define the intrinsic mechanical nature, and the coherence of various pure compacted tablets using both the nanoscopic indentation and the confined die compaction results. Data for seven different kinds of pharmaceutical drugs and excipients, composing alpha lactose, microcrystalline cellulose (Avicel PH 102), acetylsalicylic acid (Aspirin), dicalcium phosphate, magnesium carbonate, acetaminophen (Paracetamol) and pre-gelatinized starch are reported. The powders were compacted to various ultimate normal stresses ranging between 25 and 246 MPa in instrumented (force/displacement) singled ended axial compression in a cylindrical die with planar punch. The planar surfaces of these compacted tablets were nano-indented. The results clearly show that the coherence and the intrinsic nature of the tablets may be defined in a more comprehensive manner using interpretations of the nano-indentation rather than the uniaxial compaction data. The various data are consistent with the magnitude of the tensile strength of the compacts.     

Influence of feedstock preparation on ceramic injection molding and microstructural features of zirconia toughened alumina

Feedstocks for ceramic injection molding of ZTA containing 90 vol.% of sub-μm alumina and 10 vol.% of zirconia nanopowder were prepared by different processing techniques. Feedstocks were prepared by mixing in a sigma-blade kneader and subsequent homogenizing by twin-screw extrusion or shear roll compaction. Two other feedstocks were previously bead milled and subsequently processed by the same procedure. Compounding technology strongly influences the injection molding behavior and microstructures of the final product. Despite higher energy input of the shear roll compactor, powder agglomerates cannot be completely avoided. Pre-milling is effective to disperse and deagglomerate ceramic powders. Injection pressures of feedstocks from pre-milled powders were about 200 bar lower compared to pressures needed for non-milled feedstocks. Present feedstock preparation methods are feasible to produce homogeneous feedstocks, which strongly influence microstructures. In order to produce high solid loaded sub-μm/nm feedstocks, processing methods, pre-treatment and solid content have to be carefully chosen.     

Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

This paper discusses how the hydrophobicity of lubricated pharmaceutical formulations is affected by process variables such as shear rate and strain. Hydrophobicity is a critical property that affects the dissolution of powder formulations, tablets and capsules as well as the performance of tablet coating and granulation operations. In this paper, hydrophobicity is measured using a modified Washburn method. Results show that, in the absence of lubricant, the hydrophobicity of powders does not change substantially as a function of shear rate or strain. However, when magnesium stearate is present (concentrations studied here range between 0.5% and 2%), hydrophobicity increases as a function of strain, shear rate and lubricant concentration. Observed changes range over several orders of magnitude, readily explaining common “overlubrication” observations of delayed drug dissolution.     

Ambient temperature compaction of polycarbonate powder

Solid-state processing of polymer powders through compaction and sintering has potential advantages over conventional polymer processing methods; however, pressureless sintering of compacted polymer powders has often been unsuccessful. Room temperature compaction of polycarbonate (PC) powder was studied in an effort to better understand the fundamental mechanisms that control polymer compaction and sintering. It was found that differences in the degree of physical aging affect the compaction behavior of PC powder. The results presented in this paper show that the degree of physical aging of thermoplastic polymer powders, which can be influenced by commonly used powder handling operations such as drying and long term storage, can ultimately affect the ability of the powder to be successfully compacted at room temperature.     

Study of the effects of feed frames on powder blend properties during the filling of tablet press dies

This paper studies systematically the effect of a feed frames, a device used in rotary tablet presses to drive the powders into compression dies, on the properties of the powders entering the tablet press dies. The work focused on the effect of blend composition, feed frame parameters (blade speed, residence time), and rotary die disc parameters (die disc speed, die diameter) on the flow pattern, uniformity of die filling, applied shear, and the flow properties of pharmaceutical blends. The flow pattern suggests a stratified filling of the dies and therefore, non-uniform properties of the tablets. The amount of powder entering the dies depended on blend flow properties, feed frame speed, and dies disc speed. In addition, blend properties changed significantly as the powder flowed through the feed frame. The flowability of lubricated blends improved significantly as the number of feed frame blade passes increased, decreasing in turn the RSD of the die filling weight.     

Pressureless sintering of polycarbonate powder compacted at ambient temperature

Solid-state processing of polymer powders through compaction and sintering has potential advantages over conventional polymer processing methods. However, pressureless sintering of compacted polymer powders has been unsuccessful. In a previous paper (2), room temperature compaction of polycarbonate powder was studied to better understand the fundamental mechanisms that control polymer compaction. This paper focuses on the pressureless sintering of room temperature compacted polycarbonate powder. Thermomechanical analysis was used to characterize the dependence of dimensional recovery on time, temperature, and compaction pressure for compacts formed from both aged and unaged polycarbonate. It was found that all polycarbonate compacts exhibited irreversible expansion when heated to relatively low temperatures (～ 50°C), with large-scale expansion occurring near its glass transition temperature. It was concluded that irreversible expansion of polymer compacts is driven by entropic factors. Therefore, parameters that affect the degree of particle deformation during compaction also affect the degree of dimensional recovery that occurs during pressureless sintering.     

Compaction of ceramic powders

A review is given of the mechanical quantities of interest in die compaction, in relation to a number of experiments on the bulk and wall stresses, displacements, deformation and density changes that occur during the compaction of powders, illustrated by results on iron oxide and ferrite samples. Single particle and bulk deformation both show a pronounced failure. Below failure a density increase of up to 20% may be obtained by applying shear stress. This accounts for the considerable density variation near the walls or discontinuous plungers.     

Localized particle fracture during compression of materials expected to undergo plastic deformation

When powders are compressed in a die during tablet making, various stages of compaction occur, starting with rearrangement of the powder to its closest packing, followed by eventual plastic deformation or brittle fracture. Here, scanning electron microscopy has been utilized to further characterize all stages of compression. It is shown that materials, such as sodium chloride, which undergo some eventual plastic deformation undergo some form of fracture during the earlier stages of compaction due to the creation of high localized stresses acting on individual particles.     

Applying dry powder coatings to pharmaceutical powders using a comil for improving powder flow and bulk density

A method for applying nano-sized silicon dioxide guest particles onto host pharmaceutical particles (a.k.a. “dry-coating” or “nanocoating”) has been developed using conventional pharmaceutical processing equipment. It has been demonstrated that under selected conditions, a comil can be used to induce sufficient shear to disperse silicon dioxide particles onto the surfaces of host particles such as active pharmaceutical ingredients (API) without significant host particle attrition. In accordance with previous studies on dry coating, the dispersed silicon dioxide adheres to the host particle surface through van der Waals attractions, and reduces bulk powder cohesion. In this work, laboratory and pilot scale comils were used to dry coat pharmaceutical API and excipient powders with 1% w/w silicon dioxide by passing them through the mill with an appropriate combination of screen and impeller. In general, the uncoated powders exhibited poor flow and/or low bulk density. After dry coating with a comil, the powders exhibited a considerable and in some cases outstanding improvement in flow performance and bulk density. This coating process was successful at both the laboratory and pilot scale with similar improvements in flow. The superior performance of the coated powders translated to subsequent formulated blends, demonstrating the benefit of using nanocoated powders over uncoated powders. This particle engineering work describes the first successful demonstration of using a traditional pharmaceutical unit operation that can be run continuously to produce uniform nanocoating and highlights the substantial improvements to powder flow properties when this approach is used.     

Investigation of particle packing in model pharmaceutical powders using X-ray microtomography and discrete element method

This paper outlines a novel technique, based on combination of modern desktop X-ray microtomography, quantitative image processing and computer simulation using the discrete element method (DEM), to investigate randomly packed particles in an attempt to model the process of pharmaceutical tablet manufacture by powder compaction. The systems studied include glass ballotini and spheroidal micronised cellulose (Celphere), all with typical particle sizes between 180 and 300 μm. We demonstrate that X-ray microtomography (XMT) and DEM can reproduce the structure of real packing systems in three-dimensions and have the potential for further investigation of pharmaceutical processes by both modelling and experimental study. This was achieved by generating packing systems using DEM simulations that are consistent with the structural measurements made by XMT on real packed powders via the comparison of their radial distribution functions (RDFs). These results have been validated by direct volume measurements, and scanning electron microscopy (SEM) observations in terms of particle morphologies and size distribution. The result is a significant step forward for the quantitative analysis of model systems for pharmaceutical powders.     

An application for zirconia as a pharmaceutical die set

The main objective of this study was to investigate the possible use of zirconia as a material for the manufacture of punches and dies for use in tableting machines and to study its effect on ejection of tablets made from different formulations. In order to achieve this objective, the compaction properties of three commercially available direct compression excipients were examined with the help of a compaction simulator, over a range of compaction pressures using steel and zirconia tooling. The data obtained for all materials indicated that, for a particular compression speed, the work required to eject the tablet from the die, i.e., the work needed to overcome die wall friction during ejection, was lower in zirconia tooling than steel tooling. Scanning electron microscopy (SEM) was employed to investigate the excipients powders and compact surfaces for contrasting particle morphology before and after compaction. Electron probe microanalysis (EPMA) was also carried out on the representative tablets compacted at high speed using zirconia tooling and no shedding of zirconia into the tablets was detected.     

Heterogeneities and defects in powder compacts and sintered alumina bodies visualized by using the synchrotron X-ray CT

The uniaxial die compaction and sintering is an important industrial production method for metal and ceramic components. While submicron- and nano-sized powders are finding increasing use for making dense materials with finest grain sizes, the uniformity of microstructure, and then, the reliability of the products depend on the heterogeneity in powder packing structure. Here we applied the synchrotron X-ray multiscale-CT to characterize the complex domain structures, i.e., agglomerates, in powder compacts, and revealed how heterogeneous distribution of fine residual pores is formed by the differential sintering of agglomerates by using a submicron alumina powder as a model. A crack-like defect was identified as the largest defect. This defect was formed along the boundary between a plate-shaped agglomerate and its surroundings. A technique was also proposed to visualize the heterogeneous distribution of residual pores by using SEM. These characterization methods will open up new possibilities for the optimization of ceramic processing.     

Discrimination limit between mean gray values for the prediction of powder concentrations

Powder mixing is one of the most impacting steps in the handling of pharmaceutical powders for tablet production due to its strong effect in the properties and potency of the tablets. The monitoring of this process to detect the required mixing end point so that adequate properties and potency on the tablets are achieved requires continuous analysis of the powder concentration. However, its complex dynamics requires fast and accurate methods to determine the concentrations.Image analysis has already been shown to be suitable for this application. The objectives of this work were to further demonstrate its applicability to bright as well as dark powders, to determine the discrimination limit of the used vision system between powder's Mean Gray Values (MGV) in mixtures, and to develop a mathematical model to accurately predict calibration curves with minimum adjustable parameters. The study was emphasized for bright powders in the region of MGV between 255 and 140 and for dark powders in the region between 139 and 0. Mixtures of powders with difference in density greater than 0.3 g/cm³ showed considerably deviation in the prediction of concentrations. The discrimination limit between MGV attained was between 21 and 17 for both bright and dark powders. Below this range, unacceptable residuals larger than 8% w/w were obtained.