Binary Powder Mixtures Research Articles

Understanding Excipient-Induced Crystallization of Spray-Dried Amorphous Solid Dispersion

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies—binary powder mixture, binary compact, and bilayer tablets—were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility.

Compaction Properties of Particulate Proteins in Binary Powder Mixtures with Common Excipients.

The increasing interest in protein- and peptide-based oral pharmaceuticals has culminated in the first protein-based products for oral delivery becoming commercially available. This study investigates the compaction properties of proteins in binary mixtures with common excipients up to 30% (w/w) of particulate protein. Two model proteins, lysozyme and bovine serum albumin, were compacted with either microcrystalline cellulose, spray-dried lactose monohydrate, or calcium hydrogen phosphate dihydrate at two different compaction pressures. Compared to the compacted pure materials, a significant increase in the tensile strength of the compacts was observed for the binary blends containing lysozyme together with the brittle excipients. This could be attributed to the increased bonding forces between the particles in the blend compared to the pure materials. The use of bovine serum albumin with a larger particle size resulted in a decrease in tensile strength for all the compacts. The change in the tensile strength with an increasing protein content was non-linear for both proteins. This work highlights the importance of considering the particulate properties of protein powders and that protein-based compacts can be designed with similar principles as small-molecules in terms of their mechanical tablet properties.

Handheld and benchtop vis/NIR spectrometer combined with PLS regression for fast prediction of cocoa shell in cocoa powder

The fermented and dried cocoa beans are peeled, either before or after the roasting process, as peeled nibs are used for chocolate production, and shell content in cocoa powders may result from economically motivated adulteration (EMA), cross-contamination or misfits in equipment in the peeling process. The performance of this process is carefully evaluated, as values above 5% (w/w) of cocoa shell can directly affect the sensory quality of cocoa products. In this study chemometric methods were applied to near-infrared (NIR) spectra from a handheld (900–1700 nm) and a benchtop (400–1700 nm) spectrometers to predict cocoa shell content in cocoa powders. A total of 132 binary mixtures of cocoa powders with cocoa shell were prepared at several proportions (0 to 10% w/w). Partial least squares regression (PLSR) was used to develop the calibration models and different spectral preprocessing were investigated to improve the predictive performance of the models. The ensemble Monte Carlo variable selection (EMCVS) method was used to select the most informative spectral variables. Based on the results obtained with both benchtop (R2P = 0.939, RMSEP = 0.687% and RPDP = 4.14) and handheld (R2P = 0.876, RMSEP = 1.04% and RPDP = 2.82) spectrometers, NIR spectroscopy combined with the EMCVS method proved to be a highly accurate and reliable tool for predicting cocoa shell in cocoa powder. Even with a lower predictive performance than the benchtop spectrometer, the handheld spectrometer has potential to specify whether the amount of cocoa shell present in cocoa powders is in accordance with the Codex Alimentarius specifications.

Evaluation of three non-linear packing density models on micropowder mixtures

The formulation of powders often requires an optimized packing density of the granular skeleton which takes into account the desired properties. More accurate than the conventional linear models, three non-linear packing density models are evaluated from published data on binary or ternary mixtures of alumina powders, glass microbeads, siliceous microaggregates: the Compressible Packing Model (CPM), the 3-parameter Particle Packing Model (3PPM), the Theoretical Packing Density Model (TPDM). Depending on the models, they involve a compaction index K and certain particle interactions: the loosening effect a and possibly the critical cavity size ratio x0 from which it appears, the wall effect b and the wedging effect c. The CPM (with a, b, K), by incorporating only 2 interaction functions for a and b, reduces its versatility but is efficient for siliceous. The 3PPM (with a, b, c), by incorporating 9 interaction functions, adapts well to the various micropowders with however a lower performance for the siliceous for which the packing densities predicted in “compacted” conditions are lower than in “uncompacted” conditions. The TPDM (with a, b, K, x0) is effective for all types of micropowders and generates the best statistical indicators.

LiBa2AlO4: A new lithium barium aluminate having an oxygen tetrahedral framework

Single-crystal grains of the new oxide LiBa2AlO4 were obtained from a sample that had been partially melted by heating a compact of a binary oxide powder mixture having a Li:Ba:Al molar ratio of 4:5:1 ​at 1173 ​K. Single-crystal X-ray diffraction analysis demonstrated that this oxide had a trigonal superstructure (hexagonal lattice with a ​= ​5.7879(2) Å and c ​= ​13.2456(6) Å, space group P3121) formed by an ordered Li and Al arrangement. The c-axis period in this structure was found to be approximately twice as long as that in BaZnO2, the space group of which is also P3121, and a three-dimensional framework constructed by sharing all vertices of Li- and Al-centered oxygen tetrahedra. This structure can be derived from the perovskite (ABO3)-type structure via the orderly replacement of BO6 octahedra with LiO4 and AlO4 tetrahedra. Polycrystalline samples of LiBa2AlO4 were synthesized by heating compacts having stoichiometric compositions at 1173 ​K. The relative dielectric constant and dielectric loss values observed for a polycrystalline sample at room temperature were 8.3 and 0.004, respectively. The second harmonic generation intensities for LiBa2AlO4 and BaZnO2 were found to be 4.4 and 19.4 times greater than the value for quartz, respectively.

Influence of the drug deformation behaviour on the predictability of compressibility and compactibility of binary mixtures

Various studies investigate the predictability of the compressibility and compactibility of tablet formulations based on the behaviour of the pure materials. However, these studies are limited to a few materials so far probably because of the complexity of the powder compaction process. One approach preventing the excessive increase in complexity is the extension of the investigations from pure materials to binary powder mixtures. The focus of this study is on the predictability of the compressibility and compactibility of binary mixtures consisting of an active pharmaceutical ingredient (API) and the excipient microcrystalline cellulose. Three APIs with markedly different deformation behaviour were used. The API concentration and type are systematically varied. For all three material combinations it is found that the in-die compressibility of the binary mixtures can be precisely predicted based on the characteristic compression parameters of the raw materials using the extended in-die compression function in combination with a volume-based linear mixing rule. Since the tablet porosity (out-of-die) also follows a linear mixing rule, the predictability can be further extended using the method of Katz et al. In contrast, the influence of the API concentration on compactibility or rather on tablet tensile strength is non-linear and strongly dependent on the deformation behaviour of the API, making the predictability more difficult. Neither the approach of Reynolds et al. nor this of Kuentz and Leuenberger are able to predict the compactibility when clear deviations from a linear mixing rule appear.

Evaluation of gravitational consolidation of binary powder mixtures by modified Heckel equation

Consolidation of powders by tapping is an important quality test but it is time and material consuming, which encourages the use of mathematical modelling. This article aims to study this gravitational consolidation dynamics by using nine binary mixtures consisting of cellets and powdered microcrystalline cellulose (MCC102), differing in size, shape, and consolidation properties. To describe the correlation between number of taps and powder bed density/ porosity, the modified Heckel equation. (MH) was newly introduced and compared to the models by Kawakita (KW) and Varthalis & Pilpel (VP). High coefficients of determination were observed by applying the traditional KW model up to 80% of cellets, while a comparable fitting adequacy was obtained with the MH equation up to 50% of cellets in the mixtures. An increased content of MCC102 increased fitting adequacy in the MH and KW model, whereas a nearly opposite mixture trend was observed for the VP model. • Three models were used to study the consolidation dynamics of binary mixtures. • A cellet concentration-dependent relationship was noted for the Hausner ratio. • The Kawakita model fitted consolidation dynamics well up to 80% ( w /w) of cellets. • The modified Heckel model fitted the data comparably up to 50% (w/w) of cellets. • The best but opposite mixture trend was noted with Varthalis & Pilpel model.

Batch versus continuous blending of binary and ternary pharmaceutical powder mixtures

The material properties of excipients and active pharmaceutical ingredients (API's) are important parameters that affect blend uniformity of pharmaceutical powder formulations. With the current shift from batch to continuous manufacturing in the pharmaceutical industry, blending of excipients and API is converted to a continuous process. The relation between material properties and blend homogeneity, however, is generally based on batch-wise blending trials. Limited information is available on how material properties affect blending performance in a continuous process. Here, blending of API and excipients is studied in both a batch and a continuous process. Homogeneity of the resulting mixtures is analyzed, which reveals that the impact of material properties is very different in a continuous process. Where parameters such as particle size, density and flowability have significant impact on blending performance in a traditional batch process, continuous blending is more robust resulting in uniform blends for a large variety of blend compositions.

Electrical conductivity of porous binary powder mixtures

Simultaneous data of the quasi-static compaction and electrical conductivity of porous, binary powder mixtures have been collected as a function of bulk density. The powder mixtures consist of a metal conductor, either titanium or iron, an insulator, and pores filled with ambient air. The data show a dependency of the conductivity in terms of relative bulk density and metal volume fraction on conductor type and conductor particle characteristics of size and shape. Finite element models using particle domains generated by discrete element method are used to simulate the bulk conductivity near its threshold while the general effective media equation is used to model the conductivity across the compression regime.

Gravity mass powder flow through conical hoppers ‐ Part I: A mathematical model predicting the radial velocity profiles of free‐flowing granular systems as a function of cohesion and adhesion properties

AbstractIt has been demonstrated that the concentration, velocity profiles, and residence time distribution (RTD) of a binary powder mixture flowing under gravity‐driven conditions can be evaluated via near‐infrared spectroscopy (NIRS). Contrary to a classical fluid flow profile, a granular flow profile was proven to be a function of cohesion and adhesion powder mixture properties. The present work aimed to develop a semi‐empirical equation inspired by the radial flow profile equation used for classical fluids. It achieves this by introducing the effect of powder friction properties as internal (particle‐particle) and external (particle‐hopper wall) friction angles. The developed equation shows good agreement with the experimental results using various hopper angles and two types of free‐flowing granular systems. The knowledge gained from the developed equation is intended to predict flow behaviour in conical hoppers as a function of flowing powder adhesion and cohesion parameters. Combining such knowledge with residence time distribution and the radial concentration profiles would make it possible to evaluate the expected extent of segregation, which could lead to prohibitive deviations in the production of pharmaceutical solid dosage forms.

Particle size, compaction characteristic and tablet strength of spray-dried fermented jackfruit pulp - microcrystalline cellulose binary powder mixture

The tableting properties for fermented spray dried jackfruit (FJP) and microcrystalline cellulose (MCC) powders were studied. 25% FJP + 75% MCC, 50% FJP + 50% MCC and 75% FJP + 25% MCC binary powder mixtures were compacted into tablet form at various compaction pressures ranging from 15.1 to 73.8 MPa. The properties were compared to pure FJP and MCC tablets. The addition of MCC resulted in a higher particle size and the increased in the plastic work of the tablet. The best ratio of FJP-MCC binary tablet was found to be at 25% FJP + 75% MCC where the tablet showed the highest tensile strength. In conclusion, the addition of MCC to FJP improved the compaction characteristics and the tablet mechanical strength.

Influence of temperature on thermo physical properties of non-prototype material (CaO-Fe2O3, 21:79 by wt. %) for nuclear

In severe accident management, the integrity of the containment structure is a key point to focus the study related to severe accident scenarios that need knowledge of thermo-physical properties of material composition. In the present nuclear accident scenario, nuclear severe accident management is one of the challenging tasks to mitigate the phenomena occurring inside the reactor pressure vessel (RPV). Numerous studies have been done in the past to predict the severe accident phenomena and tried to explore the incidence by using different prototype and non-prototype (simulant) materials. In this context, an initial effort has been made to study the actual phenomena during an accident scenario with non-prototype material CaO-Fe 2 O 3 . Initially, the present work involved the study of the material CaO-Fe 2 O 3 powder for thermo-physical property analysis and later, the study will be carried out via melt cool ability of this material in a hypothetical nuclear reactor for analysis and mitigation of nuclear severe accident phenomena. The non-eutectic binary powder mixture of CaO and Fe 2 O 3 has prepared manually by mixing in a mortar for 40 minutes in the ratio of 21:79 by wt. % (21C79F; C refers to CaO and F refers to Fe 2 O 3 ) which has been confirmed by the phase diagram. Further, pallets were prepared of the non-eutectic binary mixture and heat-treated at 1000°C, 1100°C, and 1200°C for 3 hours in a programmable furnace. The powder form of heat-treated pellets was characterized to analyze thermo-physical properties and to validate as a simulant material (non-prototype) used for the predictive study of a nuclear severe accident. The thermal properties, phase analysis, and morphological studies of the CaO-Fe 2 O 3 (21:79 by wt. %) have been reported in the current research work and analyzed accordingly.

Impact of powder composition on processing-relevant properties of pharmaceutical materials: An experimental study

In this work, we studied the influence of powder composition on packing density and other processing-relevant properties of binary mixtures, including powder flowability. Binary mixtures of pharmaceutical powders with different particle size ratios, α and varying fractions of large and small particles were analyzed systematically. Mixtures of three excipients and one API with different composition (2, 5, 10, 30, 50, 70, 90, 95 and 98 wt%) were prepared in a Turbula mixer. Powders with different properties and particle size distribution were chosen, in order to obtain three binary mixtures with different size ratios. Then, macroscopic powder properties including bulk (poured) and tapped density (BD and TD) were measured. A powder rheometer was used to measure the flow function coefficient (ffc), cohesion, compressibility and permeability of the binary mixtures. We considered experimentally three classes of binary mixtures, which are characterized by two critical ratios of particle diameter: the critical size ratio of entrance (αc) and the critical size ratio of replacement (αr), where αc = 0.154 and αr = 0.741. Below the critical size ratio of entrance (αc), the particle asymmetry (ratio between large and small particle diameters) is high and small particles can fill the voids between larger ones. Between αc and the critical size ratio of replacement (αr), the smaller particles are too large to fit in the voids between larger particles (packing structure changes). Above αr, the particles are more or less symmetric in size and overall packing structure does not change by mixing the particles. Our experiments show that there is a non-linear and non-monotonic dependence of all relevant properties on composition for powder mixtures that have an α < αr. This non-linear behavior is even more significant for strongly asymmetric binary mixtures with α < αc. We argue that this behavior is related to the composition dependence of random packing of particulate systems. Our results have relevance to pharmaceutical particle processing operations where constant powder mixture properties are needed to ensure quality standards are met; such operations include capsule or die filling during tableting, and the continuous feeding of powders via screw feeders. Our results suggest that for pharmaceutical particle processing operations, where constant powder mixture properties are a prerequisite for process robustness, the size ratio of API and excipient particles, α should not be smaller than αr = 0.741.

Modeling Mechanochemical and Structural Transformations in a Binary Powder Mixture

Based on the constructed mathematical model, the macrokinetics of the formation of particles of mechanocomposites in a machined powder mixture is studied. The areas of different process modes making it possible to obtain a final product with the specified characteristics are identified.

Mathematical model of gas-free combustion of a binary powder mixture with allowance Marangoni convection

A macroscopic mathematical model has been developed for the gas-free combustion of a binary reaction mixture with allowance for thermocapillary convection of a low-melting reagent. The model includes equations as follows: mass balance of reaction substances, chemical transformation, melt motion, thermal conductivity. Melt formed during the melting of one of the components is believed to move in the porous carcass of the mixture due to thermocapillary forces. The dynamics of changes in temperature, chemical conversion depth, melt fraction and porosity are numerically calculated in a gasless combustion wave. Depending on the main parameters characterizing the process, conductive, convective, and mixed modes of synthesis front propagation are revealed. Analytical relationships are derived to estimate the combustion rate for these modes. An approximate criterion that reveals the synthesis mode from the structural and physicochemical parameters of the binary mixture is found.

Experimental investigation on flow properties of biomass and pulverized coal binary powder mixtures

Co-gasification of coal with biomass is a novel way to utilize biomass energy and is a new research focus in clean coal technology. A thorough knowledge of the flow properties of biomass and coal binary mixtures is critical for proper processing of feedstocks to solve annoying flow problems which frequently occur in the equipment. In this paper, the flow properties (angle of repose, packing properties, and gravity discharge rate) of different biomass materials and pulverized coal binary powder mixtures were analyzed experimentally with a powder comprehensive characteristic tester and a gravity discharge experimental facility. The effects of the mixture ratio on the flow properties of different binary powder mixtures were investigated. Results indicate that the effects of the mixture ratio on the angle of repose for mixtures with different biomass species are different. For different biomass species, the bulk densities and tapped densities of their mixtures with coal decrease with increased mixture ratio. In the range of 0 ∼ 50% biomass mass content, as the mixture ratio increases, the discharge rates of different mixtures first increase, then decrease. When the biomass mass content is larger than 50%, arching phenomenon can be observed near the hopper outlet. A modified prediction model was proposed for the discharge rates of mixtures, with an error range from −45% to +25%.

Multi-Material Additive Manufacturing – Recycling of binary Metal Powder Mixtures by Screening

Multi-material additive manufacturing by laser powder bed fusion enables arbitrary material composition in components and thus opens new design possibilities. During the manufacturing process utilized powders are mixed and arising cross-contaminations are a hindrance for powder reuse. This paper investigates the possibility to process binary metal powder mixtures of different particle size distributions, which can be sorted and recycled by screening. Two different material combinations are processed over three multi-material manufacturing cycles and powder purities in the range of parts per thousand foreign particles can be achieved. Furthermore, material flow is calculated and general applicability of the recycling process is evaluated.

Biomachining properties of various metals by microorganisms

Abstract The biomachining properties of five pure metals (Cu, Co, Fe, Sn, and W) and four sintered components made from binary powder mixtures (Cu-Co, Cu-Fe, Cu-Sn, and Cu-W) were synthetically studied under the same conditions. The material removal rate (MRR) in the machining process was recorded. The surface roughness (Sa), topography, and element distribution of the surface were compared before and after machining. The cross-sections of machined surfaces from nine samples were also observed. The electrochemical corrosion resistance of the five pure metals was evaluated by potentiodynamic polarization curves. The experimental results showed that the MRR of all samples presented good linear behavior in the machining process with different slopes. Sa of all samples increased from below 0.1 μm to 0.3–5.4 μm after machining. Material removal mechanisms involved in the biomachining process were also explored. The MRR of pure metals was mainly affected by the electrochemical corrosion resistance of the material. However, the generation of a reaction layer could reduce the MRR for the pure Co. The MRR of sintered components was affected by the reaction processes between the binary powder mixtures in the sintering process. Three material removal mechanisms were proposed for the sintered components corresponding to the different reaction processes.

Tuneable Magneto-Resistance by Severe Plastic Deformation

Bulk metallic samples were synthesized from different binary powder mixtures consisting of elemental Cu, Co, and Fe using severe plastic deformation. Small particles of the ferromagnetic phase originate in the conductive Cu phase, either by incomplete dissolution or by segregation phenomena during the deformation process. These small particles are known to give rise to granular giant magneto-resistance. Taking advantage of the simple production process, it is possible to perform a systematic study on the influence of processing parameters and material compositions on the magneto-resistance. Furthermore, it is feasible to tune the magneto-resistive behavior as a function of the specimens’ chemical composition. It was found that specimens of low ferromagnetic content show an almost isotropic drop in resistance in a magnetic field. With increasing ferromagnetic content, percolating ferromagnetic phases cause an anisotropy of the magneto-resistance. By changing the parameters of the high pressure torsion process, i.e., sample size, deformation temperature, and strain rate, it is possible to tailor the magnitude of giant magneto-resistance. A decrease in room temperature resistivity of ~3.5% was found for a bulk specimen containing an approximately equiatomic fraction of Co and Cu.

Wetting of binary powder mixtures.

The wetting process involved when a liquid droplet comes into contact with a mixture of particles is a complex phenomenon which is often understood by reference to Cassie-Baxter theory. However, various authors have applied the Cassie-Baxter theory for the prediction of contact angles on two-component mixtures without success. We hypothesise that the main difficulty in applying the Cassie-Baxter theory to mixtures is that if the particles differ in size, it is possible for the small particles to coat the large particles, so reducing the available surface area of the large particles. This leads to the view that bulk volume fractions are not good estimates of surface fractions of the components within the mixture. We argue that the Cassie-Baxter theory over represents the influence of large particles and that below a certain critical volume fraction they exert no influence. We present a simple geometrical model that relates the critical surface coverage volume fraction to the Sauter mean particle size of the binary mixture components. As a consequence, the wetting behaviour can be determined from the bulk volume fractions and the calculated critical surface coverage volume fraction, by means of a simple geometric model. We show that the simple model describes the five two-components systems reported here and a further four systems reported in the literature, irrespective of whether the larger or small particles are hydrophobic/hydrophilic. With this model, it is possible to predict the wetting behaviour of mixtures of particles that coat each other using very simple characterisation methods, so reducing the development time in the creation of formulations in the pharmaceutical industry.