Binary Powder Mixtures Research Articles

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

Investigating the effect of shape on particle segregation using a Monte Carlo simulation

A Monte Carlo simulation has been used to investigate the segregation potential of a range of particulate systems under conditions in which the particles undergo high amplitude low frequency shaking. These systems involve a wide range of binary powder mixtures in which complex particle shapes have been investigated, including plates and rods which represent the real world materials encountered in pharmaceutical systems such as those which include crystalline components. Previous simulations on the segregation propensity of systems with different shapes were limited to spheres and spherocylinders, with relatively low vibrational amplitude drops. A commercial computer application for particle packing—called MacroPac—has been successfully employed here, as it has been able to model systems that are more complex where the shape variation is much wider. These simulations apply to the case of macroscopic particles, in the absence of air resistance and inter-particle forces. For non-spherical shapes, an ‘effective size’ which relates to the radius of gyration of the particles is determined. Our studies indicate that with high amplitude low frequency shaking, in a mixture of particles with different shapes but with equal volumes, the particles with the larger ‘effective size’, which tend to have a lower packing fraction, segregate to the top.

Promoter effect of vanadia on Co/Mo/Al2O3 catalyst for deep hydrodesulfurization via the hydrogenation reaction pathway

Vanadia containing alumina (Vx-Al2O3) was prepared by the co-precipitation method and used as a catalyst support for Co and Mo oxide (Co–Mo/Vx-Al2O3) in the hydrodesulfurization (HDS) reaction. Incorporation of vanadia in the support shifted the reaction mechanism from the direct desulfurization (DDS) pathway to the hydrogenation (HYD) pathway, and hence promoted the activity of Co and Mo oxide for the HDS reaction of the most sterically hindered compound, 4,6-dimethyldibenzothiophene. Detailed catalyst characterization and catalyst testing showed that the promoter effect of vanadia is due to the synergetic effect of the formation of V–Mo sulfide. A binary powder mixture with intimate contact of Co–Mo/γ-Al2O3 and Co–Mo/Vx-Al2O3 could facilitate a concerted reaction involving both HYD and DDS pathways. Such a binary powder mixture was shown to yield a high conversion and excellent sulfur removal efficiency for the most refractory sulfur compounds in the production of clean diesel fuels.

Binary systems of ultrafine metal powders. III. Sintering of porous strips based on binary mixtures of ultrafine nickel, copper, and cobalt powders

The paper examines the sintering kinetics of porous strips based on binary mixtures of ultrafine nickel, copper, and cobalt powders at 400-800°C under 5-20 MPa for 5-30 min. Concentration and kinetic dependences of shrinkage on sintering parameters are analyzed.

Estimating particle size effects in X-ray fluorescence spectrometry

The influence of size of particles on the X-ray fluorescence intensity for powdered substances with different sized particles is estimated, based on a simple modification of the Berry–Furuta–Rhodes formulae. Analytical expressions are obtained for the model of a powder substance consisting of particles of various sizes distributed randomly in the sample volume. The results of calculations by these expressions agree fairly well with experimental data for binary powder mixtures. The particle size effect on X-ray fluorescence for the powders presented is considerably more than one could be predicted by the models proposed earlier.

The modified outflow funnel — A device to assess the flow characteristics of powders

Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of powder mixtures. During the blending process the glidants adsorb successively at the surface of the host particles and thus lead to a reduction of attractive forces. A large variety of flow additives based on silicon dioxide is commercially available, but not all glidants are just as well suited for each technological problem or each cohesive bulk powder. To assess the improvement of the flowability parameters caused by a glidant a classification system and an adequate measuring device is needed. We would like to present a new measuring device to evaluate the flow enhancing potency of glidants. The modified outflow funnel features a stirrer that acts in the region of bulk arches obstructing the outflow process of a cohesive powder. By destruction of the bulk arches powder outflow is enabled and the time needed for emanation can be measured as a parameter of the flow properties. In addition other measuring parameters like the force needed to destroy the bulk arches are capable to evaluate the flowability of the powder mixture. Binary powder mixtures consisting of corn starch and flow regulator were blended in a Turbula® mixer for a defined period of time. The flow regulators were represented by fumed silica and a selection of various types of SIPERNAT ® precipitated silica provided by Evonik Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized with a modified outflow funnel, Hausner Ratio and a shear tester.

광섬유-탐침과 근적외선(NIR) 분광기를 이용한 약제분말 유동층 혼합공정의 인라인 모니터링 연구

Since the quality of final products is significantly affected by the homogeneity of powder mixture, the powder blending process has been regarded as one of the critical pharmaceutical unit processes, especially for solid dosage forms. Accordingly, the monitoring to determine a blending process' end-point based on a faster and more accurate in-line/on-line analysis has attracted enormous attentions recently. Among various analytical tools, NIR (near-infrared) spectroscopy has been extensively studied for PAT (process analytical technology) system due to its many advantages. In this study, NIR spectroscopy was employed with an optical fiber probe for the in-line monitoring of fluid-bed blending process. The position of the probe, the ratio of binary powder mixture, the powder size differential and the back-flush period of the shaking bag were examined as principal process parameters. During the blending process of lactose and mannitol powders, NIR spectra were collected, corrected, calibrated and analyzed using MSC and PLS method, respectively. The probe position was optimized. A reasonable end-point was predicted as 1,500 seconds based on 5% RSD value. As a consequence, it was demonstrated that the blending process using a fluid-bed processor has several advantages over other methods, and the application of NIRS with an optical fiber probe as PAT system for a fluid-bed blending process could be high feasible.

Description of the dependence of intensity of x-ray fluorescence on the particle size of powder samples and pulp during x-ray fluorescent analysis

The dependence of intensity of x-ray fluorescence on particle size for powdered and pulplike media is described using a general analytical expression. The expression is obtained for a model of a powder medium consisting of particles of various sizes distributed randomly in the sample bulk. This expression involves expressions for the fluorescence intensity for homogeneous and pulplike media as limiting cases. The results of calculations by these expressions agree satisfactorily with the literature and experimental data for binary powder mixtures. The model allows one to evaluate the effect of the particle size of the powder on the fluorescence intensity for a multicomponent polydispersed powder medium.

Electrode Properties of Nanostructured and Amorphous Mg<sub>1.75</sub>Nb<sub>0.25</sub>Ni Compound Produced by Mechanical Alloying

Nb addition was found to be beneficial to the electrode properties of mechanically alloyed Mg2Ni-based product in 6M KOH solution. Formation of Mg2Ni-based nanocrystalites occurred after 15 and 5h of milling using the initial binary and ternary powder mixtures with stoichiometric compositions of Mg2Ni and Mg1.75Nb0.25Ni, respectively. Further milling of the ternary mixture resulted in the formation of an amorphous phase which became dominant after 30h. Negative electrode made from ternary product after 20h of milling exhibited the highest initial discharge capacity and the longest discharge life. This electrode showed to have a microstructure consisting of nanocrystalline Mg2Ni and an amorphous phase.

AN ELECTROCHEMICAL INVESTIGATION OF NANOCRYSTALLINE Mg2Ni0.75Nb0.25 COMPOUND SYNTHESIZED BY MECHANICAL ALLOYING

The effects of mechanical alloying on the microstructure of binary and ternary powder mixtures with stoichiometric compositions of Mg 2 Ni and Mg 2 Ni 0.75 Nb 0.25 were studied, respectively. Also, the electrode properties of the milled products were investigated in 6M KOH solution. X-ray diffraction and scanning electron microscopy of the milled products showed the formation of Mg 2 Ni -based nanocrystallites after 15 and 10h of milling using the initial binary and ternary mixtures, respectively. It was found that partial substitution of Nb for Ni has beneficial effect on the formation kinetic of nanocrystalline Mg 2 Ni . Longer milling times resulted in the formation of an amorphous phase. A relatively high discharge capacity of 350mAhg-1 was measured for the electrode made up of the ternary milled product after 20h. Also, the ternary milled product showed longer discharge life. This ternary electrode showed a microstructure consisting of Mg 2 Ni nanocrystallites and an amorphous phase. Nb substitution for Ni was found to be beneficial to electrode properties of the milled products.

Binary mixtures of ultrafine metal powders. II. Rolling of ultrafine powders into porous sheets

The paper examines the possibility of producing porous sheets by rolling binary mixtures of ultrafine powders of nickel, copper, and cobalt. The effect of the rolling rate on the thickness and porosity of sheets and on the specific surface area of powders after rolling is studied. The best rollability is shown by nickel and copper powders and by powders produced from mechanical mixtures of formates.

Precipitated silica as flow regulator

Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of the powder mixtures. The primary particles of the flow regulators exist in the form of huge agglomerates which are broken down into smaller aggregates during the blending process. These smaller aggregates adsorb at the surface of the solid's grains and thus diminish attractive Van-der-Waals-forces by increasing the roughness of the host's surface. In most cases amorphous silica is used as flow additive but material properties like particle size or bond strength influence the desagglomeration tendency of the agglomerates and thus the flow regulating potency of each silica. For some silica types we will show that the differences in their flow regulating potency are due to the rate and extent by which they are able to cover the surface of the host particles. Binary powder mixtures consisting of a pharmaceutical excipient and an added flow regulator were blended in a Turbula ® mixer for a defined period of time. As pharmaceutical excipient corn starch was used. The flow regulators were represented by a selection of amorphous silicon dioxide types like a commercial fumed silica and various types of SIPERNAT ® precipitated silica provided by Evonik-Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized by means of a tensile strength tester. The reduction of tensile strength with the blending time can be correlated with an increase in fragmentation of the flow regulator.

Development of new Al-based nanocomposites by mechanical alloying

Al-based binary (Al–Mg) and ternary (Al–Mg–Zr) elemental powder mixtures were mechanically alloyed to develop new Al–Mg–Zr nanocomposite materials. The phase evolution was studied in the as-milled and heat-treated powders by XRD and TEM/EDS analyses. For the binary Al–Mg alloy, the predominant phase was an Al(Mg) solid solution (SS) and an amorphous phase was not possible to be synthesized. Upon adding 5 at.% Zr to the Al–10Mg blended powder, some free Mg was present in addition to the formation of an Al(Zr,Mg)SS, which transformed to the Al 3Zr intermetallic after annealing. When the Zr content was increased a nanocomposite of a solid solution and an intermetallic was obtained with considerable improvement in terms of structural stability and hardness. The presence of an oxide phase at 35% Zr might be responsible for the increased hardness in this particular alloy.

On-line tools for microscopic and macroscopic monitoring of microwave processing

Direct monitoring of temperature, chemistry and microstructure is required to understand microwave heating in more detail, in order to fully exploit the unique features this non-equilibrium processing method can offer. In this paper, we show first that microwave radiometry can be used to follow volumetrically the thermal trajectory of microwave-heated aluminium powder. In-situ Raman spectroscopy is then shown to evidence thermal gradients between diamond and silicon grains in a binary powder mixture. Finally, perspectives and preliminary results of microstructural analysis obtained from X-ray microtomography are presented.

Effect of SiC Powder Characteristic on the Rheological Properties of Feedstock

In this study, the effect of SiC powder characteristic on the rheological properties of the feedstock was investigated. It was found that the viscosity of the feedstock decreased with the increase of the particle size. For the binary powder mixtures, the viscosity of the feedstock decreased with the increase of the particle size ratio of the larger particle to finer particle, which is attributed to the increase of the tap density of the powder.

Development of directly compressible powders via co-spray drying

Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility, powder hygroscopicity, flowability, and compactability. The influence of process parameters during spray drying on the compaction behaviour of drug/excipient mixtures was investigated via Heckel analysis. Erythritol, lactose, maltodextrin, and mannitol were efficient in co-spray drying with acetaminophen. However, lactose mixtures showed poor flowability. Spray dried mixtures containing mannitol and erythritol were characterised as non-hygroscopic, highly dense, and good flowing powders. Mannitol increased tablet tensile strength in contrast with the poor compactability of erythritol. Maltodextrin was selected for further experiments because it provided excellent tablet tensile strength. The use of erythritol, maltodextrin and mannitol in binary drug/excipient mixtures resulted in high process yields. Compacts of erythritol, mannitol, and maltodextrin were characterised by higher tablet tensile strength at higher spray drying temperatures due to the increased particle fragmentation of erythritol and mannitol mixtures and to the increased plastic deformation of maltodextrin formulations. A combination of erythritol, maltodextrin, and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression.

The Effect of Binary Mixture Composition and Magnesium Stearate Concentration on the Hiestand Tableting Indices and Other Related Mechanical Properties

Maltodextrins were chosen as model excipients because maltodextrins possess a series of molecular weights that showed systematically changing consolidation mechanisms. As maltodextrin molecular weight increases, the plasticity of the material increases. Three commercial grades of Maltrin® (M040, M100, and M150) were used to prepare binary powder mixtures (M040-M150 and M040-M100). For each mixture, magnesium stearate was added at concentrations of 0%, 0.16%, 0.32%, 0.48%, and 0.64%. The Hiestand Tableting Indices and other related mechanical properties were used to quantify the effects of magnesium stearate addition on the compaction properties of the binary mixtures. Linear relationships were observed between the Hiestand Bonding Indices and the compositions of the compacts in the absence of magnesium stearate. However, the Hiestand Bonding Indices were related to compact compositions in polynomial fashion when magnesium stearate was present in the binary mixtures. The Hiestand Brittle Fracture Indices varied with compact compositions in polynomial fashion with and without magnesium stearate.

Predictions of tensile strength of binary tablets using linear and power law mixing rules

There has recently been an increased interest in predicting the tensile strength of binary tablets from the properties of the individual components. In this paper, measurements are reported for tensile strength of tablets compressed from single-component and binary powder mixtures of lactose with microcrystalline cellulose (MCC), and lactose with two types of silicified microcrystalline cellulose (SMCC and SMCC-HD), which are different in compressibility. Measurements show the tensile strength increases with the relative density for single powders, and both with the relative density and the mass fraction of cellulose in the mixtures. It was also observed, for binary mixtures compacted at 50 and 150 MPa, that there was a slight variation in porosity with the mass fraction of celluloses. The predictions of the tensile strength of binary tablets from the characteristics of the single-components was analysed with the extended Ryshkewitch–Duckworth model by assuming both linear and power law mixing rules for the determination of the parameters “tensile strength at zero porosity and bonding capacity constant”. As consequence, four models were analysed and compared with measurements using criteria based on the standard deviation from the mean values. Results showed a good prediction using a linear mixing rule combined with the power law. However, as the predictions of these models depend on the powders and the porosity range for the characterization of single-components, none of them can be systematically considered as being the best to predict binary behaviour from data for individual powders.

Considerations about the theoretically expected crushing strength of tablets from binary powder mixtures: Double layer tablets versus arithmetic additivity rule

The theoretically expected breaking strength of tablets from powder mixtures is often calculated by the weighted arithmetic mean from the breaking strength of the single components, which corresponds to a linear interpolation. The validity of this additivity of fracture strength shall be evaluated by the underlying model of parallel couplings. It assumes the components linked in parallel with respect to the direction of loading during diametrical strength testing. Parallel couplings were experimentally realised by the preparation of double layer tablets from crystalline and spray-dried lactose on the one hand and from maltitol and metamizol-sodium on the other. Constant total true volumes of the single substances and of layered powders in varying ratios of true volume were compressed on an eccentric tabletting machine to constant geometric mean punch force. Simulated crushing profiles of parallel couplings were derived from force–displacement profiles measured during diametrical compression of the one-component tablets. At given finely graded deformation levels, the forces exerted by the components during loading were added in the proportion of the true volume fractions of the components in the coupling. The results from the experiments and from the simulations are in good accordance. They demonstrate that a linear change of the crushing strength in dependence on the true volume fraction of the components can only be assumed if the single components deform to the same extent up to the point of fracture. This behaviour was approximately found with the parallel lactose system. In all other cases it must be expected that the crushing strength of parallel systems will be lowered beneath the weighted arithmetic mean values or even below the crushing strength of the single components. The latter was observed with the maltitol–metamizol combinations. Thus, if tablets from binary powder mixtures exhibit a crushing strength depression, this is not necessarily an indication of weak bonding between the components or of structural defects.

Preparation of Ni paste using binary powder mixture for thick film electrodes

To achieve high dispersed Ni paste/thick film for BME-MLCC (base metal electrode multilayered ceramic capacitor) internal electrode, dispersion properties of paste/thick film using binary Ni powder mixtures were investigated. The viscosity of Ni paste containing binary powders is higher than that of Ni paste containing mono-sized powders regardless of mixing ratio of different sized Ni powders. On the other hand, the Ni paste containing 75 wt.% 500 nm powders and 25 wt.% 200 nm powders had the smallest surface roughness (Ra = 0.07 μm and Rmax = 0.61 μm). After drying at 100 °C in an air atmosphere, the microstructure of dried thick film exhibited an overall flatness on the cross-section and few voids on the top surface. These effects may be explained by the filling of grooves and voids among large powders during three-roller milling process.