Powder Compression Research Articles

Correlation between the powder characteristics and particle morphology of microcrystalline cellulose (MCC) and its tablet application performance

A quantitative approach is described to finding the correlation between the MCC application performance in tablets, which is key to pharmaceutical applications, and two kinds of powder features, 1) physical properties and 2) morphology, using multiple stepwise regression analysis to eliminate the statistically insignificant factors. The powder compressibility index was shown to be the primary factor affecting the tablet performance. However, no single powder physical property correlated with tablet performance in samples of varied particle shape. By contrast, a strong correlation was observed between the fractal dimension/shape factors and the main parameters affecting the tablet application performance. Circularity, the key shape factor, was shown to be the main indicator of tablet performance in drug delivery applications. The closer the particles to spherical shape, the shorter their disintegration time and greater the dissolution rate. These morphological effects were demonstrated across a wide range of particle sizes and shapes.

Densification behaviour of pure copper processed through cold pressing and binder jetting under different atmospheres

PurposeBinder jetting is a promising route to produce complex copper components for electronic/thermal applications. This paper aims to lay a framework for determining the effects of sintering parameters on the final microstructure of copper parts fabricated through binder jetting.Design/methodology/approachThe knowledge gained from well-established powder metallurgy processes was leveraged to study the densification behaviour of a fine high-purity copper powder (D50 of 3.4 µm) processed via binder jetting, by performing dilatometry and microstructural characterization. The effects of sintering parameters on densification of samples obtained with a commercial water-based binder were also explored.FindingsSintering started at lower temperature in cold-pressed (∼680 °C) than in binder jetted parts (∼900 °C), because the strain energy introduced by powder compression reduces the sintering activation energy. Vacuum sintering promoted pore closure, resulting in greater and more uniform densification than sintering in argon, as argon pressure stabilizes the residual porosity. About 6.9% residual porosity was obtained with air sintering in the presence of graphite, promoting solid-state diffusion by copper oxide reduction.Originality/valueThis paper reports the first systematic characterization of the thermal events occurring during solid-state sintering of high-purity copper under different atmospheres. The results can be used to optimize the sintering parameters for the manufacturing of complex copper components through binder jetting.

Air entrapment during tablet compression – Diagnosis, impact on tableting performance, and mitigation strategies

Air entrapment during powder compression, a phenomenon that can cause tablet defects upon decompression and ejection, was diagnosed for celecoxib powder by comparing its in-die elastic recovery profiles with and without precompression prior to the main compression. Without precompression, the elastic recovery of celecoxib compacts significantly increased from ∼4% at a main compaction pressure of 150 MPa to ∼14% at and above 200 MPa. The large increase in elastic recovery is eliminated when a precompression step is employed. The deaeration of powder by precompression resulted in higher tablet strength, accompanied by lower tablet porosity. Thus, precompression is an effective strategy to mitigate the deleterious effects of air entrapment in tablet manufacturing. We also found that, although entrapped air caused significantly higher elastic recovery, it does not affect the plasticity parameter derived from an in-die Heckel analysis.

Formulation and Optimization of Rifampicin and Quercetin Laden Liquisolid Compact: In-Vitro and In-Vivo Study

The major objective of this study is to create rifampicin and quercetin-containing liquisolid compacts with improved gastrointestinal absorption and dissolving properties. Propylene glycol, PEG 200, and Tween 20 were chosen as ideal non-volatile liquid carriers to create the required formulations because of their increased drug solubility. In an attempt to create a free-flowing, compressible powder, the liquisolid formulations were then combined with a carrier and coating material. In order to c

Effects of Powder Particle Size on Fatigue Performance of Laser Powder-Bed Fused Ti-6Al-4V

In powder-based metal additive manufacturing, one key specification that needs to be precisely optimized is the particle shape and size distribution of metallic powders. Particle shape and size distribution influences the flowability of the powder and the uniformity of powder bed density (i.e. packing state of the powder). These eventually affect the porosity, which ultimately influences the fatigue performance of the fabricated parts. Therefore, it is essential to understand the effect of powder characteristics on the fatigue behavior before additively manufactured parts can be used in load-bearing, safety-critical applications. The current study aims at assessing the effects of powder particle size and morphology on mechanical properties and fatigue response of laser beam powder bed fused (LB-PBF) Ti-6Al-4V; an alpha-beta workhorse alloy of the titanium family. Several Ti-6Al-4V powder batches with different size distributions are used to fabricate the parts employing an EOS M290 machine. Powder characteristics, including flowability, compressibility, cohesion, size, and shape morphology, are investigated to reveal the differences between the two tested powder batches. Porosity levels and mechanical testing results are compared among specimens fabricated from different powder batches and the differences are explained based on variations in powder characteristics.

Upotreba simulatora kompaktiranja za karakterizaciju kompresije praškova - prednosti i ograničenja

Compaction simulators are designed as machines which can provide an in-depth analysis of the powder compaction process. Characterization of the powder compression and compaction process, as well as material characterization, play an important role in the formulation and manufacturing process design and development, as well as in creating a strong knowledge basis for the scale-up of the tablet compression and troubleshooting in further stages of the product lifecycle. Although compaction simulators are designed to simulate the compression process on high-speed tablet-presses, with the advantages of a small quantity of material needed and highly sophisticated instrumentation, there are certain limitations in the extrapolation of the process parameters from these machines to high-speed rotary tablet presses. However, the advantage of the use of compaction simulators for studying basic compression and compaction mechanisms, identification of critical material attributes and critical process parameters ranges, and their relations with tablet characteristics and critical quality attributes of pharmaceutical products is clear, compared to the use of small excentre tablet presses, and complementary to the use of small rotary tablet presses. This scientific paper provides an overview and examples of the different advantages provided by the instrumentation of compaction simulators, including certain limitations in their exploitation.

New methods for theranostic radioisotope production with solid targets at the Bern medical cyclotron

The production of theranostic radionuclides using solid targets is challenging and requires an accurate knowledge of the production crosssections as well as the energy, positioning and focusing of the beam. A research program is ongoing at the 18 MeV Bern medical cyclotron, equipped with a Solid Target Station (STS) and a 6 m Beam Transfer Line (BTL) ending in a separate bunker with independent access. A novel target coin was designed and built to irradiate compressed powder pellets, together with a compact focalization system to optimize the irradiation procedure. Furthermore, methods were developed to measure the beam energy, the production cross-sections and the EoB-activity.

Streamlining tablet lubrication design via model-based design of experiments

In oral solid dosage production through direct compression powder lubrication must be carefully selected to facilitate the manufacturing of tablets without degrading product manufacturability and quality (e.g. dissolution). To do so, several semi-empirical models relating compression performance to process operating conditions have been developed. Among them, we consider an extension of the Kushner and Moore model (Kushner and Moore, 2010, International Journal Pharmaceutics, 399:19) that is useful for the purpose, but requires an extensive experimental campaign for parameters identification. This implies the preparation and compression of multiple powder blends, each one with a different lubrication extent. In turn, this translates into a considerable consumption of Active Pharmaceutical Ingredient (API), and into time-consuming experiments. We tackled this issue by proposing a novel model-based design of experiments (MBDoE) approach, which minimizes the number of optimal blends for model calibration, while obtaining statistically sound parameters estimates and model predictions. Both sequential and parallel MBDoE configurations were compared. Experimental results involving two placebo blends with different lubrication sensitivity showed that this methodology is able to reduce the experimental effort by 60–70% with respect to the standard industrial practice independently of the formulation considered and configuration (i.e. parallel vs. sequential) adopted.

Orally Disintegrating Tablet Manufacture via Direct Powder Compression Using Cellulose Nanofiber as a Functional Additive.

In recent years, orally disintegrating (OD) tablets have been continuously improved to increase efficacy. Herein, we focused on the benefits of cellulose nanofiber (CNF), a highly functional material, in OD tablet manufacturing. We studied its effects on the physical properties of tablets during manufacture. The analyzed tablet formulations included different content CNF (0-50%; 6 preparations), lactose hydrate, acetaminophen, and magnesium stearate (Mg-St). We measured the angles of repose and evaluated the flowability of the powder. Tablets were prepared on a tabletop and rotary tableting presses, whereafter their weight, drug content, hardness, friability, and disintegration time were evaluated. Although CNF addition slightly reduced powder flowability, continuous tableting was feasible via direct powder compression. Tablet hardness (~40 N) was comparable between CNF-containing (20%) tablets and those prepared with crystalline cellulose under 10 kN compression force. Disintegration time (~30 s) was similar between CNF-supplemented tablets and those supplemented with low-substituted hydroxypropyl cellulose, crospovidone, or croscarmellose sodium. At higher CNF fractions, tablet hardness increased, while friability decreased. Adding ≥30% CNF prolonged the tablet disintegration time. To set the optimized manufacturing condition for ensuring the desired tablet physical properties, we created contour plots for evaluating the effects of CNF concentration and compression force on hardness and disintegration time. A CNF concentration of 10-20% and a compression force of 12-13 kN would allow for the preparation of tablets with a hardness ≥30 N and a disintegration time ≤60 s. Altogether, addition of CNF to the OD tablet formulation for direct powder compression enhanced hardness and disintegration.

Evaluation of ablation plume temperature for laser intensity and alumina powder particle density in alumina reduction

We considered the application of lunar regolith for the construction of a lunar base. To obtain aluminum as building materials, alumina powder reduction was performed using 1-kW-class continuous-wave diode laser ablation. The possibility of reduction, and the temperature dependences of the ablation plume on the laser intensity, ambient pressure, and particle density were investigated, and surface analysis was conducted using SEM and XPS. The laser intensity, ambient pressure, and particle density were set as 0.32–1.3 GW m−2, 10–100 kPa, and 16%–56%, respectively. Alumina reduction was verified by observing the 394- and 396 nm spectra of Al(I). The plume temperature increased with laser intensity in the range of 2700–4500 K. We achieved temperatures of 5200 K and 1000 K higher than with the CO2 laser by powder compression. Spheres that appeared to be aluminum were observed on the irradiated surfaces. However, this could not be proved because of the aluminum oxide layer.

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Powder Compaction Dies and Compressibility of Various Materials

Powder Compaction Dies and Compressibility of Various Materials

Liquisolid Compacts Technique of Poor Water Soluble Drugs: An Overview

Liquisolid technique is new and promising method that can use to enhance the dissolution rate of poorly water soluble drugs. Liquisolid compact technique is based upon the dissolving the drug in a suitable non-volatile solvent by using carrier and coating material for the conversion of acceptable flowing and compressible powders. By applying the mathematical models the carrier and coating materials optimized. In this case the drug is almost solubilised in the solvent or molecularly dispersed state which contributes the enhanced drug dissolution.

Poly-ε-Caprolactone/Halloysite Nanotube Composites for Resorbable Scaffolds: Effect of Processing Technology on Homogeneity and Electrospinning.

Polycaprolactone (PCL)/halloysite composites were prepared to compare the effect of homogenization technology on the structure and properties of the composites. Halloysite content changed from 0 to 10 vol% in six steps and homogeneity was characterized by various direct and indirect methods. The results showed that the extent of aggregation depends on technology and on halloysite content; the size and number of aggregates increase with increasing halloysite content. Melt mixing results in more homogeneous composites than the simple compression of the component powders or homogenization in solution and film casting. Homogeneity and the extent of aggregation determines all properties, including functionality. The mechanical properties of the polymer deteriorate with increasing aggregation; even stiffness depends on homogeneity. Strength and deformability decreases drastically as the number and size of aggregates increase. Not only dispersed structure, but also the physical state and crystalline structure of the polymer influence homogeneity and properties. The presence of the filler affects the preparation of electrospun fiber scaffolds as well. A part of the filler is excluded from the fibers while another part forms aggregates that complicates fiber spinning and deteriorates properties. The results indicate that spinning is easier and the quality of the fibers is better if a material homogenized previously by melt mixing is used for the production of the fibers.

Ionic Transportation Characteristics in All Solid-State Battery Electrode with Sulfide and Halide Solid Electrolytes

Bulk-type all solid-state lithium-ion battery electrodes are manufactured by compressing composite powder of active material and solid electrolyte powder. This compression increases contact area between the powder particles and reduces ion transportation resistance in the electrode. In many cases, mechanical characteristics of the solid electrolyte and active material are different, and complex stress distribution is generated in the compressed composite powder. In authors previous studies, ion transportation characteristics of electrode with soft active material and hard active material are studied experimentally and numerically. The electrode with soft active material has high ionic conductivity due to high stress is applied to the solid electrolyte in the electrode and high contact area between solid electrolyte powder is achieved. As showed from this study, Young’s modulus of active material is an important factor of ionic transportation in electrode of all solid-state battery. Based on this result, solid electrolyte the Young's modulus of the solid electrolyte is also an important factor of ionic transportation in electrode. Therefore, in this study, we conducted experiments and numerical simulation of ionic conductivity of the electrode with changing the Young’s modulus of the solid electrolyte to elucidate the influence of Young’s modulus of the solid electrolyte on ionic transportation characteristics of the electrode.Two solid electrolytes are employed in this study. One is sulfide solid electrolyte of Li5.5PS4.5Br1.5. This solid electrolyte is made by mechanical milling with vibration mill and heat treatment. The other is halide solid electrolyte of Li3InCl6. This halide solid electrolyte is made with wet process from LiCl and InCl3. These solid electrolytes are mixed with dummy active material of ZrO2 and nylon. The dummy active materials used to simulate only ionic transportation by a solid electrolyte and mechanical conditions. Young’s modulus of ZrO2 is about 200 GPa and is almost same as Young’s modulus of hard active materials such as LCO and NCM. Young’s modulus of nylon is about 6 GPa and is almost same as Young’s modulus of soft active materials such as graphite. From these two solid electrolytes and two dummy active materials, four dummy electrodes.Fig.1 illustrates effective Young’s modulus of Li5.5PS4.5Br1.5 powder and Li3InCl6 powder measured with changing the applied pressure from 0MPa to 100MPa. From this figure, the Young’s modulus of Li5.5PS4.5Br1.5 is from 100MPa to 700MPa and that of Li3InCl6 is about half of Li5.5PS4.5Br1.5. Therefore, it can be said that, compared to sulfide solid electrolyte, halide solid electrolyte is relatively soft solid electrolyte.Fig.2 illustrates relative ionic conductivity as a function of the volumetric fraction of dummy active material. Here, the ionic conductivity is normalized by the ionic conductivity of pure solid electrolyte (= 0% volumetric fraction of dummy active material). As shown in fig.2 (a), the relative ionic conductivity of sulfide solid electrolyte and halide solid electrolyte are almost same when the dummy active material is soft (nylon). However, in the case with hard dummy active material (ZrO2), as shown in fig.2 (b), the relative ionic conductivity with halide solid electrolyte is lower than that with sulfide solid electrolyte at high dummy active material volumetric fraction. With hard active material, mechanical pillar is generated by active material in the electrode and strain of the solid electrolyte is low. In the case with sulfide solid electrolyte, relatively high stress can be generated with the low strain, but in the case with halide solid electrolyte, stress is relatively low with the low strain. This is because, as shown in fig.1, Young’s modulus of sulfide solid electrolyte is higher than that of the halide solid electrolyte, and high stress for high ionic conductivity can be generated even with low strain in the case with sulfide solid electrolyteThis Study is supported by JKA foundation (2021M-188) Figure 1

Enteric-coated bacteriophage tablets for oral administration against gastrointestinal infections

Intestinal Pseudomonas aeruginosa is highly problematic in immunocompromised patients such as those in intensive care units in hospitals. Phage therapy is an attractive alternative or supplementary therapy to antibiotics as it not only kills multidrug-resistant bacteria, but also minimises the disruption of gut microflora. Solid oral dosage forms (i.e., tablets) have the potential to effectively deliver viable phages to the gastrointestinal tract, but formulation studies have been scarce. In this study, Pseudomonas-targeting phage PEV20 was used as a model to produce tablets suitable for oral delivery by utilising industry-scale tablet compression and tablet coating machines. Phage tablets were produced by (i) spray drying of phages, (ii) direct compression of the phage powders into tablets, and then (iii) tablet coating. The resulting phage tablets had negligible phage titre reduction throughout the process and passed the British Pharmacopeia tests, including friability, weight variation, disintegration and dissolution of the tablets as well as weight gain and disintegration (in 0.1 M HCl and pH 7.4 phosphate buffer) of coated tablets. The developed formulation method can be utilised to produce tablets containing other phages and phage cocktails that are effective against enteric bacterial infections.

Calculation of Spectral Optical Constants Using Combined Ellipsometric and Reflectance Methods for Smooth and Rough Bulk Samples.

Spectra of the optical constants n and k of a substance are often deduced from spectroscopic measurements, performed on a thick and homogeneous sample, and from a model used to simulate these measurements. Spectra obtained for n and k using the ellipsometric method generally produce polarized reflectance simulations in strong agreement with the experimental measurements, but they sometimes introduce significant discrepancies over limited spectral ranges, whereas spectra of n and k obtained with the single-angle reflectance method require a perfectly smooth sample surface to be viable. This paper presents an alternative method to calculate n and k. The method exploits both ellipsometric measurements and s-polarized specular reflectance measurements, and compensates for potential surface scattering effects with the introduction of a specularity factor. It is applicable to bulk samples having either a smooth or a rough surface. It provides spectral optical constants that are consistent with s-polarized reflectance measurements. Demonstrations are performed in the infrared region using a glass slide (smooth surface) and a pellet of compressed ammonium sulfate powder (rough surface).

Study on effect of SuperTab 40LL on compression characteristics of musk sustained-release mini-tablets based on mathematical models

In this paper, co-processed lactose SuperTab 40 LL was selected as fillers to study the preparation of musk sustained-release mini-tablets in the Xihuang multiple-unit drug release system. Musk sustained-release tablets containing different proportions of SuperTab 40 LL and MCC were prepared under various pressures, and then the compressibility and compactibility of these prescriptions were evaluated by Walker, Heckel and Ryshkewitch-Duckworth equations. In addition, the fluidity of the prescriptions was evaluated by parameters of Kawakita equation. There was a comprehensive analysis of the effect of SuperTab 40 LL on musk sustained-release mini-tablets combined with the appearance of SuperTab 40 LL and their tensile strength. The results shown that SuperTab 40 LL had better compression process through the Heckel equation, and the direct compression process of drug powders with excipients can be analyzed by the Kawakita and Ryshkewitch-Duckworth equations. As a new type of co-processed lactose, SuperTab 40 LL had a good fluidity and compactibility. SuperTab 40 LL may undergo particle crushing and plastic deformation during the compression process, which increased the contact area and bonding sites between the particles, and aggregated and shaped the mixed powder easy. Moreover, MCC showed a synergistic effect, and the combined application with SuperTab 40 ll could effectively improve the fluidity and compressibility of the musk sustained-release powder. When the ratio of SuperTab 40 LL and MCC was 2∶1, musk sustained-release mini-tablets had a high drug loading capacity and good compactibility in line with the design objectives.

Properties of Orthopaedic Cements Biomechanically Little Affected by Exceptional Use of Liquid Antibiotics.

ObjectivesTo specify the concentration of the liquid antibiotics to be added to polymethylmethacrylate (PMMA) and its impact on the quality of the spacer is the purpose of this study with liquid clindamycin added to different cements.MethodsIn the present study, eight different cement mixtures were prepared and investigated. In the following, number 1 indicates the references, 2 all cements after liquid clindamycin was added to the liquid cement compound, 3 all cements after liquid clindamycin was added to the cement powder, and 4 all cements after liquid clindamycin was added to the cement dough. After curing, cements were filled into metal moulds and a pressure of 3 bar was maintained for 30 min. Mechanical investigations were carried out according to ISO 5833 (2002) and DIN 53435 (2007). For microbiological tests, standardized cylindrical mouldings (diameter: 25 mm, height: 10 mm) were produced and incubated in 10 ml buffer solution at room temperature for 24 h. All eluates were generated by spreading previously established suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes and methicillin‐resistant Staphylococcus aureus (MRSA) with a 0.5 McFarland turbidity standard.ResultsApparently, we found that in all investigated cases, the admixture of liquid antibiotic negatively affected the mechanical characteristics of the cement mould. Among the various test groups, the influence on the ISO compression strength and ISO flexural modulus of the investigated test groups was only minimal when liquid clindamycin was added to cement liquid. Compared to admixing of liquid clindamycin into cement powder or dough ISO compression strength and ISO flexural modulus and flexural strength showed the maximum reduction. The efficacy against chosen germs was reduced as well when liquid antibiotic was admixed instead of powder. This admixture of liquid anti‐infective agents resulted in a 234% enhanced elution after 10 days 29 a negative effect on the inhibition zones were detected during the previous period.ConclusionThe admixture of powdery antibiotic is preferable to liquid antibiotics. If no powdery antibiotic is available, we can recommend the admixture of liquid antibiotic to liquid cement prior to dough production in case powdery antibiotics cannot be used. However, we discourage the admixture of liquid antibiotic to cement powder or cement dough during early low viscose phase.

Effect of the Ag addition on the compressibility, sintering and properties of Ti6Al4V/xAg composites processed by powder metallurgy

This work investigates the fabrication of Ti6Al4V/xAg composites processed by powder metallurgy. An atomized Ti6Al4V powder was blended with 0, 5, 10, 15 and 20 vol% of Ag particles, compacted in a die, and sintered above Ag melting point. The compressibility of the mixtures was analyzed, and the sintering kinetics was evaluated by dilatometry tests. The characterization of sintered samples by microtomography, SEM and diffraction analysis allowed determining the effect of Ag amount on the sintering process and on microstructural changes arising during sintering. The mechanical properties of sintered materials were investigated by microhardness. The compressibility of Ti6Al4V powder was found to be improved by adding soft Ag particles, which resulted in denser packing and larger plastic deformation. The densification during compaction can be predicted by Heckel model and the rule of mixture. It was next found that sintering was driven by volume diffusion in the solid state for Ag content lower than 10 vol% and involved a liquid phase for Ag content higher than 15 vol%. In the latter case, the liquid fills the interconnected pores under the action of capillary forces as the quantity of liquid increased. The microstructure was composed mainly of α-Ti, Ti2Ag, and Ag, which filled the pores between Ti6Al4V particles. Microhardness data showed a maximum value with 20 vol% of Ag. This value is similar to those reported for highly dense Ti6Al4V. It has thus proved that close to full-dense Ti6Al4V/20Ag composites can be processed by powder metallurgy.