Vibratory Ball Mill Research Articles

Efflux Inhibitor Bicalutamide Increases Oral Bioavailability of the Poorly Soluble Efflux Substrate Docetaxel in Co-Amorphous Anti-Cancer Combination Therapy.

Many anti-cancer drugs are difficult to formulate into an oral dosage form because they are both poorly water-soluble and show poor permeability, the latter often as a result of being an intestinal efflux pump substrate. To obtain a more water-soluble formulation, one can take advantage of the higher solubility of the amorphous form of a given drug, whereas to increase permeability, one can make use of an efflux pump inhibitor. In this study, a combination of these two strategies was investigated using the co-amorphous approach, forming an amorphous mixture of two anti-cancer drugs, docetaxel (DTX) and bicalutamide (BIC). The efflux substrate, DTX, was combined with the efflux inhibitor, BIC, and prepared as a single phase co-amorphous mixture at a 1:1 molar ratio using vibrational ball milling. The co-amorphous formulation was tested in vitro and in vivo for its dissolution kinetics, supersaturation properties and pharmacokinetics in rats. The co-amorphous formulation showed a faster in vitro dissolution of both drugs compared to the control groups, but only DTX showed supersaturation (1.9 fold) compared to its equilibrium solubility. The findings for the co-amorphous formulation were in agreement with the pharmacokinetics data, showing a quicker onset in plasma concentration as well as a higher bioavailability for both DTX (15-fold) and BIC (3-fold) compared to the crystalline drugs alone. Furthermore, the co-amorphous formulation remained physically stable over 1.5 years at 4 °C under dry conditions.

Whey proteins as stabilizers in amorphous solid dispersions

Whey proteins are extensively used as nutritional supplements but have so far not been investigated as co-formers for amorphous solid dispersions (ASD) to enhance the solubility and dissolution rate of poorly water soluble drugs. In this study, whey protein isolate (WPI) and whey protein hydrolysate (WPH) were each mixed with three poorly water soluble drugs (indomethacin: IND, carvedilol: CAR and furosemide: FUR) and prepared as ASDs at 50% (w/w) drug loading using vibrational ball milling. Subsequently, solid state characteristics, dissolution rate and physical stability of the obtained samples were analyzed. All ASDs showed a significant increase in their glass transition temperatures, as well as faster dissolution rates and higher apparent solubilities compared to both the respective pure crystalline and amorphous drugs. The saturation solubility of the drugs was increased in the presence of the whey proteins, and the investigated ASDs showed supersaturation by attaining higher drug concentrations compared to the respective saturation solubilities. Upon storage, ASDs containing IND were found to be physically stable for at least 27 months, whereas, ASDs containing CAR or FUR were stable for about 8 months and 17 months, respectively. This was a tremendous increase in physical stability compared to the pure amorphous drugs which recrystallized within less than one week. Overall, WPI and WPH proved to be promising co-formers and amorphous stabilizers in ASD formulations.

Synthesis of Ni-Ti Coatings on Different Metallic Substrates by Mechanical Alloying and Subsequent Laser Treatment

In this work, we proposed a novel mechanical alloying method to deposit Nix-Tixintermetallic coating on various metallic substrates using laser treatment. Three different substrates (Al-based alloy, Ti-based alloy, and hypoeutectoid steel) were used, and 50–70 μm thick NixTix coating was deposited during the process. For mechanical alloying, we used a self-constructed vibratory ball mill (single chamber) and for laser treatment, we used a “TrumpfTruDisk 1000” machine equipped with a four-dimensional control system “Servokon” designed specifically for experimental studies. Different laser beam intensities were used for laser operation. The cross-sectional microstructures of coatings were studied using a scanning electron microscope equipped with a Bruker energy-dispersive X-ray Spectrometer (EDS). Additional investigation of a cross-sectional area of one of the NixTix-coated samples was performed with field emission high-performance SEM and focused ion beam (FIB). Phase compositions of the obtained coatings, before and after laser treatment, were analyzed using X-Ray diffraction method. After the deposition process, the micro-hardness of the coatings was measured using a Vickers hardness tester. The structure and morphology of the obtained coatings were investigated.

Angular oscillation model to predict the performance of a vibratory ball mill for the fine grinding of grain

The development of a mathematical model of a vibratory mill made it possible to determine the regularities for the complex movement of its operating mechanisms and obtain a graphic interpretation for the kinematic, power and energy characteristics of the vibratory system. On the basis of theoretical pre-requisites, a series of experimental studies were conducted that provided an opportunity to obtain the amplitude-frequency, velocity and energy characteristics of the machine under investigation and to determine their impact upon the kinetics of the fine grinding process of the grain. As a result, rational operating parameters of the examined machine were established with minimal energy input.

Mortars prepared with mechanochemical treated asbestos-containing waste

The paper presents the results of recycling of asbestos-containing waste (ACW). It is shown that hydraulic activity of ACW is increased using mechanochemical treatment in the vibratory ball mill in presence of anionic surfactant. Experimental results show that substitution of 10% w.t. of cement on activated asbestos-containing waste leads to increasing of the compressive strength to 20%. Finally, the effect of the activated ACW on the hardening kinetics of mortars is examined.

The efficiency analysis on assistant-grinding of lignosulfonate and its modified composites

The method of vibration ball milling is applied in this paper to make research on contents of lignosulfonate and modified composites as cementgrinding aids; and studied on the influence of regularity about grinding aids on products fluidity, particle size, specific surface area and powder particle size distribution. The study showed lignosulfonatehas had better effect on the cement grinding function; the cement’s particle size and the distribution were improved, the average diameter was decreased, distribution narrowed and ultra-fine grain size increased, of the most importance, the contents of ultra-fine grain size were increased much. Among those, the effect of calcium lignosulfonate was relatively good while its modified composites performed better.

Study and development of NiAl intermetallic coating on hypo-eutectoid steel using highly activated composite granules of the Ni–Al system

Abstract NiAl intermetallic coating thickness of about 50 μm was fabricated on hypo-eutectoid steel by mechanical alloying using pre-activated Ni–Al composite granules as coating material. First, Ni and Al powders were mixed with the composition of Ni-50 at.% Al and mechanically activated in a planetary ball mill, until the composite granules of this powder mixture, having maximum activity (9 cm sec−1), were formed after 120 min of milling at 200 rpm. The composite granules were then taken out from the planetary ball mill just before the critical time, i. e. the time at which these granules synthesize and convert to an intermetallic NiAl compound. The highly activated composite granules of Ni–Al were then put into the vial of a vibratory ball mill with the substrate on top of the chamber. After mechanical alloying for 60 min in the vibratory ball mill, the composite granules were synthesized fully and heat was produced during the synthesis which helped producing a thick and strong adhesive coating of NiAl intermetallic on the steel substrate. The main advantage of this technique is that not only is time saved but also there is no need for any post mechanical alloying process such as annealing or laser treatment etc. to get homogeneous, strongly bonded intermetallic coatings. X-ray diffraction analysis clearly indicates the formation of NiAl phase. Micro-hardness of the coating and substrate was also measured. The cross-sectional microstructure of the composite granules and the final coating were studied by scanning electron microscopy.

From Molecules to Silicon-Based Biohybrid Materials by Ball Milling

Hybrid nanoparticles with a large bridging organic group were prepared by mechanochemical-assisted sol–gel reaction. Planetary ball mill (PBM) was used for the first time to access the bis-silylated precursors, containing complex functionalities (such as hydantoins or a symmetrical urea obtained from α-amino esters). The process is based on a sequential reaction pathway involving liquid-assisted grinding (LAG) and 1,1′-carbonyldimidazole (CDI)-mediated one-pot/two-step reactions. Then hydantoins and the symmetric urea were used for the one-pot preparation of the corresponding bis-silylated compounds in a vibrational ball mill (VBM), followed by the mechanochemical sol–gel preparation of biohybrid bridged silsesquioxane nanospheres of uniform size.

Deposition of the Ti-Al coatings on different metallic substrates by mechanical alloying and subsequent laser treatment

Ti-Al intermetallic coatings thickness of about 60–150 μm was fabricated on Al, Ti, and hypo-eutectoid steel substrates by mechanical alloying (MA) using a vibratory ball mill. The coatings was then laser treated to obtain homogenous and equilibrium structure. Phase composition and the cross-sectional microstructure of the coatings were investigated using X-ray diffraction and the Scanning electron microscopy respectively while chemical analysis of the coatings was carried out using Bruker energy-dispersive X-ray Spectrometer (EDS). Micro-hardness (HV) of the obtained coatings was observed to be increased more than twice after the deposition and subsequent laser treatment in comparison with microhardness of the initial substrates materials.. Surface roughness of the obtained coatings was also reduced significantly after laser treatment i.e. for Al substrate it reduced from 52 μm to 26 μm. The parameters of mechanical alloying and laser treatment used in this work provided a successful way to deposit nano-structured intermetallic coatings with homogenous and smooth surface finish and high value of micro-hardness.

Vibration Ball Milling for the Synthesis of 5'-Thioadenosine 5'-Pyrophosphate (P'→5') Adenosine (dASppA).

Using vibration ball milling, 5'-chloro-5'-deoxyadenosine (CldA) reacts cleanly with 4-methoxybenzyl mercaptan (MobSH), under basic conditions, to the corresponding thioether (MobSdA), which is isolated following precipitation and trituration. Under acidic conditions, in a one-pot, two-step process, MobSdA is transformed into 5'-deoxy-5'-(5-nitropyridyl-2-disulfanyl)-adenosine (NPySSdA). Michaelis-Arbuzov (M-A) reaction of NPySSdA with tris(trimethylsilyl) phosphite proceeds to completion within 30min as determined by 31 P NMR, and the persilylated M-A product thus formed can be stored in solution under anhydrous conditions at room temperature for several days (in contrast, the anionic phosphorothiolate monoester is labile to hydrolysis). Following evaporation, mechanochemical mixing of the crude M-A product with the nucleotide donor adenosine 5'-monophosphomorpholidate under acidic activation in the presence of additional water gives rapid hydrolytic desilylation and phosphate coupling, so that essentially complete reaction is observed after 90min and dASppA isolated following C-18 reversed phase HPLC and desalting (>99% pure as determined by monitoring at 260nm). © 2017 by John Wiley & Sons, Inc.

Strength activity and microstructure of blended ultra-fine coal bottom ash-cement mortar

Replacing Portland cement with reutilized coal combustion products can have substantial benefits to the environment as well as infrastructure. In this study, a sub-bituminous coal bottom ash is re-utilized as a cement replacement. The bottom ash was pulverized using a high energy vibratory ball mill at two different milling times to achieve a particle fineness approximately two and three-times finer, respectively, than type I cement. The workability and final setting time were found to increase by 21% and 14%, respectively, and the highest strength activity was observed to be 120% at 90days. After normalization for particle fineness, age, and binder replacement using a general linear regression model, the data suggested the bottom ash blended cement mortar had 6.8% less strength activity than a comparative fly ash blended cement mortar. Blended bottom ash-cement paste samples were observed to have densely packed CSH product composed of relatively lower Ca/Si ratio (1.37) compared to that of fly ash blended cement paste (1.43) and the control (2.27). The CH content was also observed to be significantly lower in the bottom ash blended cement paste (19.1%) when compared against the control (27.2%) and fly ash blended paste (23.3%). Within the range of experimental conditions considered here, the results suggest that a coal bottom ash can be pulverized with a high energy ball mill to produce a re-utilizable pozzolan that, depending on the powder fineness, can significantly increase the strength activity, improve the microstructure of cement mortar, and increase the cement replacement tolerances without significant reduction to compressive strength activity.

Ball milling pretreatment affects the content of fixed ammonium in soils in response to the content of exchangeable ammonium

ABSTRACTAnalysis of fixed ammonium (NH4+) in soils by the most common method requires the subsample to be ground to pass through a 100-mesh sieve. We tested a hypothesis that the ball milling pretreatment for the analysis of fixed NH4+ may influence the analytical results depending on the content of exchangeable NH4+. Five paddy soils collected from the surface layer in Japan were treated with 15N-labeled ammonium sulfate at 0, 100, 500, or 1000 mg N kg−1, incubated aerobically at 30°C for 7 days, and air-dried. Part of each soil was then ground in a vibration ball mill at 1200 rpm for 10 min as a pretreatment (BMP treatment). The samples with and without the BMP treatment were analyzed for exchangeable NH4+ and total fixed NH4+. The samples that received 0 or 1000 mg N kg−1 were also analyzed for nonexchangeable 15N (total fixed 15NH4+ plus organic 15N) and hot KCl-extractable organic N. At 0 mg N kg−1, the BMP treatment significantly decreased total fixed NH4+ in all soils and significantly increased exchangeable NH4+ in two of the five soils. The fixation of exchangeable NH4+ started to occur when its content is greater than around 300 mg N kg−1, and its ratio to total fixed NH4+ is greater than around 1.0. At 1000 mg N kg−1, the BMP treatment significantly decreased exchangeable NH4+ and significantly increased total fixed NH4+ in all soils especially two clayey, vermiculitic soils. On the average of all soils applied 1000 mg N kg−1, the increase in total fixed NH4+ explained 55% of the decrease in exchangeable NH4+, and the decrease in exchangeable NH4+ was almost equal to the increase in nonexchangeable 15N. The rest of the NH4+ unaccounted by the fixation was partly due to the transformation of exchangeable NH4+ to hot KCl-extractable organic N, because the content of hot KCl-extractable organic N was significantly increased by the BMP treatment. In conclusion, the milling treatment prior to the analysis of fixed NH4+ in soils might cause either underestimation or overestimation depending on the content of exchangeable NH4+.

Optimization of solvent-free mechanochemical synthesis of Co/Al2O3 catalysts using low- and high-energy processes

In this work, alumina-supported cobalt (Co/Al2O3) catalysts were prepared using new solvent-free mechanochemical synthesis methods: low-energy vibratory ball milling (Fritsch, Pulverisette 0) and high-energy planetary ball milling (Retsch, PM 100). γ-Al2O3 supports and Co/Al2O3 catalysts after mechanochemical treatments were characterized using a combination of techniques. The study of solid particles revealed the abrasion and fragmentation phenomena of porous γ-Al2O3 particles and pore filling under milling. Functional cobalt particles introduced by the mechanochemical synthesis were observed to be preferentially localized on the outer surface of the alumina supports. High Fischer–Tropsch reaction rates were obtained with the catalysts prepared by optimized mechanochemical synthesis conditions. The enhanced catalytic performance can be attributed to the relatively high dispersion of cobalt and the absence of inert cobalt aluminates which are usually present in the catalysts synthesized by the conventional impregnation.

Regularity and mechanism of wheat straw properties change in ball milling process at cellular scale

To investigate the change of structure and physicochemical properties of wheat straw in ball milling process at cellular scale, a series of wheat straws samples with different milling time were produced using an ultrafine vibration ball mill. A multitechnique approach was used to analyze the variation of wheat straw properties. The results showed that the characteristics of wheat straw powder displayed regular changes as a function of the milling time, i.e., the powder underwent the inversion of breakage to agglomerative regime during wheat straw ball milling process. The crystallinity index, bulk density and water retention capacity of wheat straw were exponential relation with ball milling time. Moreover, ball milling continually converted macromolecules of wheat straw cell wall into water-soluble substances resulting in the water extractives proportional to milling time.

N-Acyl Benzotriazole Derivatives for the Synthesis of Dipeptides and Tripeptides and Peptide Biotinylation by Mechanochemistry

An eco-friendly methodology for preparing Fmoc-, Z-, and Boc-N-protected dipeptides and tripeptides is described, from the corresponding N-protected-α-aminoacyl benzotriazoles and α-amino acid derivatives, with different C-terminal functionalities such as esters or amides, using vibrational ball-mill (VBM). The reactivity of a β-amino ester was also investigated. In some cases, the coupling was achieved by liquid-assisted grinding (LAG). α,α- and one α,β-dipeptide were obtained in good to excellent yields mainly by precipitation in water, resulting in an improved environmental impact compared to classical peptide synthesis in solution, as shown by green metric calculations. The method was extended to the biotinylation, via an aminohexanoyl spacer, of the pentapeptide RGDfV, which contains the well-known integrins recognition site arginine–glycine–aspartic acid (RGD) motif.

Nucleophilic displacement reactions of 5'-derivatised nucleosides in a vibration ball mill.

Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the corresponding 5′-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts.

The first example of mechanochemical synthesis of organometallic pincer complexes

The synthesis of an organometallic PdII pincer complex is realized for the first time via CH bond activation of the bis(thiocarbamate) ligand with PdCl2(NCPh)2 under mechanochemical conditions either by grinding of the reactants in a mortar or in a vibration ball mill at gram scale.

Impact of pre-treatments on properties of lignocelluloses and their accessibility for a subsequent carboxymethylation

In this issue, different chemical (alkaline and sulfite pulping, ozonolysis) and mechanical (vibratory ball milling) pre-treatments were utilized for activating wheat straw and beech sawdust prior to carboxymethylation. Detailed analysis by a range of methods, including Klason-lignin, cellulose and hemicellulose quantification, Powder-X-ray diffraction (PXRD) and attenuated total reflection (ATR) IR spectroscopy, enabled the investigation of material alterations. Subsequently, carboxymethylation was carried out with both untreated and activated materials, allowing the evaluation of activation steps by determining degrees of substitution with carboxymethyl groups (DSCM). Moreover, carboxymethylation conditions were optimized, realizing high DSCM of up to 1.05. Results further revealed that ball milling enhanced the subsequent conversion; whereas chemical pre-treatments did not effectively increase material accessibilities. Further studies on chemically untreated materials emphasized that a highly reactive surface was already generated in the course of the carboxymethylation, inter alia through the concomitant dissolution of matrix components.

Synthesis of the Ni-Al coatings on different metallic substrates by mechanical alloying and subsequent laser treatment

Abstract Ti-Al intermetallic coatings thickness of about 60–150 μm was fabricated on Al, Ti, and hypo-eutectoid steel substrates by mechanical alloying (MA) using a vibratory ball mill. The coatings was then laser treated to obtain homogenous and equilibrium structure. Phase composition and the cross-sectional microstructure of the coatings were investigated using X-ray diffraction and the Scanning electron microscopy respectively while chemical analysis of the coatings was carried out using Bruker energy-dispersive X-ray Spectrometer (EDS). Micro-hardness (HV) of the obtained coatings was observed to be increased more than twice after the deposition and subsequent laser treatment in comparison with microhardness of the initial substrates materials.. Surface roughness of the obtained coatings was also reduced significantly after laser treatment i.e. for Al substrate it reduced from 52 μm to 26 μm. The parameters of mechanical alloying and laser treatment used in this work provided a successful way to deposit nano-structured intermetallic coatings with homogenous and smooth surface finish and high value of micro-hardness.

Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers

Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this study, the feasibility of hot melt extrusion for continuous manufacturing of co-amorphous drug-amino acid formulations was examined, challenging the fact that amino acids melt with degradation at high temperatures. Furthermore, the need for an addition of a polymer in this process was evaluated. After a polymer screening via the solvent evaporation method, co-amorphous indomethacin-arginine was prepared by a melting-solvent extrusion process without and with copovidone. The obtained products were characterized with respect to their solid-state properties, non-sink dissolution behavior, and stability. Results were compared to those of spray-dried formulations with the same compositions and to spray-dried indomethacin-copovidone. Overall, stable co-amorphous systems could be prepared by extrusion without or with copovidone, which exhibited comparable molecular interaction properties to the respective spray-dried products, while phase separation was detected by differential scanning calorimetry in several cases. The formulations containing indomethacin in combination with arginine and copovidone showed enhanced dissolution behavior over the formulations with only copovidone or arginine.