Resonant Acoustic Mixing Research Articles

Simple, scalable mechanosynthesis of metal-organic frameworks using liquid-assisted resonant acoustic mixing (LA-RAM).

We present a rapid and readily scalable methodology for the mechanosynthesis of diverse metal–organic frameworks (MOFs) in the absence of milling media typically required for other types of mechanochemical syntheses. We demonstrate the use of liquid-assisted resonant acoustic mixing (LA-RAM) methodology for the synthesis of three- and two-dimensional MOFs based on Zn(ii), Co(ii) and Cu(ii), including a mixed ligand system. Importantly, the LA-RAM approach also allowed the synthesis of the ZIF-L framework that has never been previously obtained in a mechanochemical environment, as well as its Co(ii) analogue. Straightforward scale-up from milligrams to at least 25 grams is demonstrated using the metastable framework ZIF-L as the model.

Resonant Acoustic® Mixing: Processing and Safety

AbstractNew processing technologies are allowing researchers, industry and academia to probe new materials space not previously achievable. These technologies include additive manufacturing and Resonant Acoustic® Mixing (RAM) which are being demonstrated to reduce processing times, environmental impact and of course cost. With the introduction of any new technology it is imperative that users, managers and national bodies provide the resources and time to determine, understand and provide guidance associated with the safe operating envelope. Combining the RAM with energetic materials requires numerous steps and iterations to generate the required knowledge. This paper is divided into three parts; the first provides a comparison of existing process technologies for energetic materials and how the community has approached using RAM for each of the energetic material sectors. The second part of the paper provides a summary of a review on how RAM users had provided safety assurance in using the technology with energetic materials. The third part covers how the community is using fundamental and applied research to continue in understanding the technology and where the benefits may lie. It is noted that this field is young therefore information contained herein will change in the future.

Processing Studies of Energetic Materials using Resonant Acoustic Mixing Technology

Processing Studies of Energetic Materials using Resonant Acoustic Mixing Technology

Comparison of Propellant Processing by Cast‐Cure and Resonant Acoustic Mixing

AbstractIn this comparative study, a solid composite, AN/HTPB‐based propellant was prepared by conventional processing in a mechanical mixer and by applying an advanced processing technique relying on resonant acoustic mixing (RAM). After curing of the propellants, cross‐sections were prepared and characterized by scanning electron microscopy. Also the density of the propellants was measured and finally the ballistic properties were measured using chimney burner tests. The experimental results clearly showed that the oxidizer particles, the homogeneity of the propellants, the density and the burn rate properties are hardly affected by the processing method. For the propellant studied in this research, resonant acoustic mixing is a very promising, advanced processing technique that can be applied as an alternative to the conventional mechanical mixing of this high solid load propellant composition.

소리의 공명현상을 이용한 물질혼합 기술 응용 연구

소리의 공명현상을 이용한 물질혼합 기술 응용 연구

Effective dynamic properties of random complex media with spherical particles.

The effective dynamic bulk modulus and density are presented for random media consisting of particles in a viscous host fluid, using a core-shell, self-consistent effective medium model, under the large compressional wavelength assumption. These properties are relevant to acoustic or dynamic processes in nano- and micro-particle fluids including particle density determination, resonant acoustic mixing, and acoustic characterisation. Analytical expressions are obtained for the effective bulk modulus and mass density, incorporating the viscous nature of the fluid host into the core-shell model through wave mode conversion phenomena. The effective density is derived in terms of particle concentration, particle and host densities, particle size, and the acoustic and shear wavenumbers of the liquid host. The analytical expressions obtained agree with prior known results in the limit of both static and inviscid cases; the ratio of the effective bulk modulus to that of the fluid is found to be quasi-static. Numerical calculations demonstrate the dependence of the effective mass density on frequency, particle size (from nano- to micro-regime), and concentration. Herein it is demonstrated both theoretically and numerically that the viscosity, often neglected in the literature, indeed plays a significant role in the effective properties of nanofluids.

Ultra-fast fabrication of tape-cast anode supports for solid oxide fuel cells via resonant acoustic mixing technology

Abstract Herein, for the first time, we demonstrate ultra-fast fabrication of a tape casted NiO-yttria stabilized zirconia (YSZ) anode support for solid oxide fuel cells (SOFCs) using resonant acoustic mixing (RAM) technology. Due to its characteristics of non-contact and high-intensity acoustic field-assisted mixing, NiO-YSZ tape-cast slurry is prepared via a RAM process within ∼0.5 h, > 140 times faster than use of a conventional ball-milling (BM) process (∼72 h). During the RAM process, liquid binders more effectively penetrate into soft agglomerated ceramic powders and covered larger surface area than the case of BM process. The optimization of RAM procedure requires more subdivided mixing sequence and higher content of binders and plasticizers compared to that of the BM. Despite drastically reduced mixing time, the microstructures of RAM Ni-YSZ anode, quantified via a 3D reconstruction, are statistically identical to that of BM Ni-YSZ. The SOFC employing RAM Ni-YSZ anode support achieves 0.55 W/cm2 at 750 °C in peak power density and exhibits high durability for 300 h without noticeable degradation. Thus, our results demonstrate that the RAM process is a highly effective and ultra-fast mixing technology to produce high performance SOFC components.

Impact of Method of Preparation of Amorphous Solid Dispersions on Mechanical Properties: Comparison of Coprecipitation and Spray Drying

Usage of the amorphous phase of compounds has become the method of choice to overcome oral bioavailability problems related to poor solubility. Due to the unstable nature of glasses, it is clear that the method of preparation of the amorphous glass will have an impact on physical/chemical stability and in turn in vivo performance. The method of preparation can also have a profound impact on the mechanical properties of the amorphous phase. We have explored the impact of preparation method on the mechanical properties of an amorphous solid dispersion using a development compound, GDC-0810. Three methods were used to generate amorphous solid dispersions (ASDs) of 50% GDC-0810 with hydroxypropyl methylcellulose acetate succinate: (1) spray drying, (2) coprecipitation using overhead mixing, and (3) coprecipitation using resonant acoustic mixing. All 3 methods were found to generate ASDs with good phase mixing and similar glass transition temperatures. Coprecipitated ASD powders (overhead mixing and resonant acoustic mixing) demonstrated superior tabletability and flow properties when compared to the spray drying powder. Careful choice of manufacturing process can be used to tune material properties of ASDs to make them more amenable for downstream operations like tableting. Acoustic mixing has been demonstrated as a scalable new method to make ASDs through coprecipitation.

Ball-free mechanochemistry: in situ real-time monitoring of pharmaceutical co-crystal formation by resonant acoustic mixing.

Resonant acoustic mixing (RAM) is a new technology designed for intensive mixing of powders that offers the capability to process powders with minimal damage to particles. This feature is particularly important for mixing impact-sensitive materials such as explosives and propellants. While the RAM technique has been extensively employed for the mixing of powders and viscous polymers, comparatively little is known about its use for mechanosynthesis. We present here the first in situ study of RAM-induced co-crystallisation monitored using synchrotron X-ray powder diffraction. The phase profile of the reaction between nicotinamide and carbamazepine in the presence of a small amount of water was monitored at two different relative accelerations of the mixer. In marked contrast to ball-milling techniques, the lack of milling bodies in the RAM experiment does not hinder co-crystallisation of the two starting materials, which occurred readily and was independent of the frequency of oscillation. The reaction could be optimised by enhancing the number of reactive contacts through mixing and comminution. These observations provide new insight into the role of various experimental parameters in conventional mechanochemistry using liquid-assisted grinding techniques.

Shaken flasks by resonant acoustic mixing in the biosynthesis of alginate by Azotobacter vinelandii with non‐Newtonian rheological characteristics

AbstractBACKGROUNDOrbitally shaken flasks in polysaccharide‐producing bacterial cultures usually present oxygen limitations because of non‐Newtonian rheological characteristics of the resulting culture broth and bacterial respiration. Here, we present the production of alginate by Azotobacter vinelandii using a novel alternative mixing technology (resonant acoustic mixing, RAM) to increase oxygen transfer.RESULTSNo significant differences were observed in biomass growth (3.43 ± 0.61 g L‐1) with RAM frequencies between 5 and 20 g, but higher specific growth and sucrose consumption rates were found at higher frequencies (15 and 20 g). The highest alginate production (9.13 ± 0.63 g L‐1) was obtained in 20 g cultures, in which no oxygen limitation was detected, whereas intracellular reserve polymer poly‐β‐hydroxybutyrate (PHB) production was favored at low shaking frequencies (5 and 10 g), in which dissolved oxygen tension was zero for a long culture time. Cultures behave pseudoplastically, with an apparent viscosity that increases until the end of the exponential phase, and the alginate monomer ratio was approximately 1.0 in all cultures.CONCLUSIONRAM can maintain elevated oxygen transfer rates, even in non‐Newtonian high‐viscosity cultures, as in the case of alginate production by A. vinelandii. © 2017 Society of Chemical Industry

Controlled shear system and resonant acoustic mixing: Effects on lubrication and flow properties of pharmaceutical blends

PurposeLubrication is critical in pharmaceutical manufacturing of solid dosage forms. The purpose of this paper is to systematically compare and correlate the lubrication effect of two devices, a controlled shear system and a Resonant Acoustic Mixer, on the flow properties of pharmaceutical blends. MethodA model formulation was selected. Full factorial designs were conducted to examine the effect of the total strain (or total energy) and the shear rate (or power) on the powder blend flow properties. Analysis of variance (ANOVA) and effect size test using omega-squared statistics were performed. ResultsLubrication significantly improved the blend flowability. Mixing without magnesium stearate, or insufficient strain, resulted in more cohesive blends. The statistical analysis suggests that the shear rate had a minimal effect on the blend flow properties. The experimental results also suggest that although the two devices had comparable lubrication effects on the overall blend flowability, the changes of the interparticle forces in the lubricated blends were not identical. ConclusionThis study demonstrated a scientific approach to compare different lubrication processes in an objective and reproducible manner. The findings are useful for process design, development, and transfer between different equipment types and process scales.

Production of a recombinant phospholipase A2 in Escherichia coli using resonant acoustic mixing that improves oxygen transfer in shake flasks

BackgroundShake flasks are widely used during the development of bioprocesses for recombinant proteins. Cultures of recombinant Escherichia coli with orbital mixing (OM) have an oxygen limitation negatively affecting biomass growth and recombinant-protein production. With the aim to improve mixing and aeration in shake flask cultures, we analyzed cultures subjected to OM and the novel resonant acoustic mixing (RAM) by applying acoustic energy to E. coli BL21-Gold (DE3): a producer of recombinant phospholipase A2 (rPLA2) from Micrurus laticollaris snake venom.ResultsComparing OM with RAM (200 rpm vs. 7.5g) at the same initial volumetric oxygen transfer coefficient (kLa ≈ 80 h−1) ~69% less biomass was obtained with OM compared with RAM. We analyzed two more conditions increasing agitation until maximal speed (12.5 and 20g), and ~1.6- and ~1.4-fold greater biomass was obtained as compared with cultures at 7.5g. Moreover, the specific growth rate was statistically similar in all cultures carried out in RAM, but ~1.5-fold higher than that in cultures carried out under OM. Almost half of the glucose was consumed in OM, whereas between 80 and 100% of the glucose was consumed in RAM cultures, doubling biomass per glucose yields. Differential organic acid production was observed, but acetate production was prevented at the maximal RAM (20g). The amount of rPLA2 in both, OM and RAM cultures, represented 38 ± 5% of the insoluble protein. A smaller proportion of α-helices and β-sheet of purified inclusion bodies (IBs) were appreciated by ATR-FTIR from cultures carried out under OM, than those from RAM. At maximal agitation by RAM, internal E. coli localization patterns of protein aggregation changed, as well as, IBs proteolytic degradation, in conjunction with the formation of small external vesicles, although these changes did not significantly affect the cell survival response.ConclusionsIn moderate-cell-density recombinant E. coli BL21-Gold (DE3) cultures, the agitation increases in RAM (up to the maximum) was not enough to avoid the classical oxygen limitation that happens in OM shake flasks. However, RAM presents a decrease of oxygen limitation, resulting in a favorable effect on biomass growth and volumetric rPLA2 production. While under OM a higher recombinant protein yield was obtained.

High-throughput screening and scale-up of cocrystals using resonant acoustic mixing

This paper explores the effectiveness of resonant acoustic mixing RAM for screening and scale up of cocrystals. 16 cocrystal systems were selected as test cases based on previous literature precedent. A 96 well plate set up in conjunction with zirconia beads was used for cocrystal screening using RAM. A success rate of 80% was obtained in the screen for plates containing solvent or solvent plus Zirconia beads. A proof of concept production of hydrated and anhydrous cocrystals of 1:1 Theophylline Citric acid system at a 400mg scale was demonstrated using solvent and bead assisted RAM. Finally the parameters affecting the scale up of 2:1 Theophylline Oxalic acid cocrystals was explored in a systematic fashion using a Design of Experiments DOE approach. The RAM parameters of acceleration and mixing time were optimized using the DOE approach. A quantitative XRPD method was developed to determine the extent of conversion to the cocrystal when using RAM Mixing time of 2h and an acceleration of 60G were determined to be optimal. The optimized parameters were used to demonstrate scale up of 2:1 Theophylline Oxalic acid cocrystals at an 80 gram scale with a net yield of 94%. RAM is thus established as an environmentally friendly mechanochemical technique for both high throughput screening and scaled up production of cocrystals.

In-line and Real-time Monitoring of Resonant Acoustic Mixing by Near-infrared Spectroscopy Combined with Chemometric Technology for Process Analytical Technology Applications in Pharmaceutical Powder Blending Systems.

Resonant acoustic® mixing (RAM) technology is a system that performs high-speed mixing by vibration through the control of acceleration and frequency. In recent years, real-time process monitoring and prediction has become of increasing interest, and process analytical technology (PAT) systems will be increasingly introduced into actual manufacturing processes. This study examined the application of PAT with the combination of RAM, near-infrared spectroscopy, and chemometric technology as a set of PAT tools for introduction into actual pharmaceutical powder blending processes. Content uniformity was based on a robust partial least squares regression (PLSR) model constructed to manage the RAM configuration parameters and the changing concentration of the components. As a result, real-time monitoring may be possible and could be successfully demonstrated for in-line real-time prediction of active pharmaceutical ingredients and other additives using chemometric technology. This system is expected to be applicable to the RAM method for the risk management of quality.

Promising CL‐20‐Based Energetic Material by Cocrystallization

AbstractA novel cocrystal (NEX‐1) of CL‐20 and MDNT is presented herein. The CL‐20: MDNT cocrystal, obtained in high yield by resonant acoustic mixing, shows new properties versus the discrete components. This is the first example of cocrystallization of CL‐20 where the new material is less sensitive to friction than CL‐20 itself, while demonstrating similar impact and ESD sensitivity. The CL‐20: MDNT cocrystal shows promise in the production of new energetic materials of interest by the cocrystallization of well‐characterized components.

Development of Screening Methodology for the Assessment of the Agglomeration Potential of APIs

A simple screening protocol has been developed for assessing the agglomeration potential of active pharmaceutical ingredients (APIs) using resonant acoustic mixing that minimizes the quantity of API used. This methodology improves upon existing ones as it allows for multiple conditions to be screened in parallel, saving time and allowing for the study of agglomeration and optimization of the drying unit operation to take place early in development. In addition to a qualitative (visual) assessment, quantitative data can be obtained after the material has been dried therefore accounting for a measure of cake hardening. This methodology was also extended to assess the friability of the generated agglomerates and was validated using a scaled-down agitated filter dryer (AFD). The impact of particle size, particle size distribution, solvent selection, and solvent loading on the agglomeration potential for a Takeda API is also discussed which allowed for the development of an improved drying process that was suc...

Formation of Additive-Containing Nanothermites and Modifications to their Friction Sensitivity

ABSTRACTNanothermites can provide high energy densities and reaction rates but can also display extreme friction sensitivities. Additives that provide friction modification offer the potential to reduce the friction sensitivity of nanothermites. In the present work, MoS2, graphene, and hexadecane additives were dispersed in MoO3 prior to nanothermite formation with the aim of reducing friction sensitivity. Nanothermites were subsequently prepared using a palmitic acid–passivated nano-aluminum (L-Al) and additive-containing nano-MoO3 by the resonant acoustic mixing of dry powders. In general, the incorporation of additives results in a reduction in friction sensitivity with the baseline minimum ignition friction rising from 10 to 120 N using 0.5% wt/wt micrometer-sized MoS2 or 5% wt/wt hexadecane. However, the relationships between loading and performance are complex and vary by additive; for example, the friction sensitivity dependence using micrometer-diameter MoS2 displays a maximum at 0.5% wt/wt and declines to 7 N using 5% MoS2.

Characterization of resonant acoustic mixing using near-infrared chemical imaging

This study presents the first investigations on the micro-mixing properties of pharmaceutical powder blends from a resonant acoustic mixer using near-infrared chemical imaging. All experiments were done in a laboratory resonant acoustic mixer (RAM). The powder blends were studied using near-infrared chemical imaging (NIR-CI). Qualitative (i.e. chemical images) and quantitative (e.g. mean diameter of aggregates) results were obtained using this analytical method. The quantitative results were correlated to the acceleration (mixing intensity) and total mixing time. Overall, the resonant acoustic mixing performance increased with increasing acceleration and mixing time. Therefore, larger aggregates of the active pharmaceutical ingredient (API) were found at lower accelerations (mixing intensity) and shorter mixing times. Mixing in the RAM efficiently reduced the overall aggregate size of the cohesive API (semi-fine APAP, ~45μm) used in a common blend of filler (microcrystalline cellulose, ~110μm) and lubricant (magnesium stearate, ~10μm).

Effect of resonant acoustic mixing on pharmaceutical powder blends and tablets

Blending in a resonant acoustic mixer (RAM) was shown to be highly effective for low concentrations of cohesive active pharmaceutical ingredients (APIs) and lubricant (Osorio and Muzzio, 2015). However, changes in material properties of the final blend were observed. Those changes, and their effects on tablet characteristics, are discussed in this paper. Variations in particle size, powder flow properties and hydrophobicity of the blend were examined. The final blend was compressed into tablets. The tableting compression force, and tablet hardness, weight and dissolution were investigated. Overall, powder blend and tablet properties were significantly affected by acceleration, blending time and total energy input. The total energy input to the blend can be efficiently calculated within error in the RAM; this is not true for most mixers. Trends between total energy input and the material properties of the blends and tablets were obtained. Resonant acoustic mixing is a good choice for blending low concentrations of cohesive APIs. Care must be taken when blending hydrophobic lubricants in the RAM; the high energy input can adversely affect critical tablet properties such as hardness and dissolution. The known energy input can be used to predict the performance of blends and final products processed in a RAM.

Time for pairing: cocrystals as advanced energetic materials

Energetic materials that can store and rapidly release large amounts of chemical energy on demand play a vital role in both military and civilian fields. Modern energetic materials should have high density, high heat of formation and possess molecular stability that allow them to be manufactured, stored and handled safely. Recently, cocrystallization technology offers a promising platform for energetic materials to achieve a desired balance between high detonation performance and low sensitivity. This paper highlights recent developments of energetic cocrystals and details intermolecular interactions, physical parameters and detonation properties. The major part of the discussion relates to the different types of energetic cocrystals including cocrystals composed of energetic molecules and solvents, 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20)-based cocrystals and azole-based cocrystals, et al. In addition, resonant acoustic mixing (RAM) technique, bead milling and spray flash evaporation technique are also introduced as means for large-scale production of nanosized energetic cocrystals.