Resonant Acoustic Mixing Research Articles

Verification of the mixing processes of the active pharmaceutical ingredient, excipient and lubricant in a pharmaceutical formulation using a resonant acoustic mixing technology

Mixing processes are important for making high-quality pharmaceutical formulations and are related to dissolution and chemical stability in pharmaceutical manufacturing.

Shaken flasks by resonant acoustic mixing versus orbital mixing: Mass transfer coefficient kLa characterization and Escherichia coli cultures comparison

Shaken flasks are widely applied in bioprocesses due to their flexibility and ease of operation. Resonant acoustic mixing (RAM) enables non-contact mixing by the application of low frequency acoustic energy, and is proposed as an alternative to solve oxygen limitations in orbital mixing (OM). The aim of this study is to experimentally determine empirical kLa correlations for RAM and compare it with OM by its measurement at different shaking frequencies, nominal flask volumes, and filling volumes. The maximum kLa here obtained were 131.3±5.1h−1 for OM and 435.4±11.7h−1 for RAM. Empirical correlations were validated for kLa as a function of shaking frequency and superficial area/filling volume ratio and rendered adequate values for the adjusted R2 with an accuracy of ±30%. Further, we compared the Escherichia coli kinetics of growth, glucose uptake, dissolved oxygen tension (DOT), and organic acids production in RAM and OM at two equivalent initial kLa. Similar E. coli kinetics were observed at an initial kLa of 46h−1, but not at 92h−1 where differences in DOT and culture parameters were found, mainly in growth rate and biomass yield on glucose, which is the result of different oxygen transfer rates due to the increased gas pressures in RAM.

Integration of ResonantAcoustic® mixing into thermal processing of foods: A comparison study against other in-container sterilization technologies

A comparison study was carried out for thermal processing times and final product quality in three different modes of retort operation. Still retort simulation, processing with horizontal reciprocating agitation, and ResonantAcoustic® Mixing (RAM) integrated processing were used to process banana puree samples at different °Bx (degree Brix) values (ranging from 16.6 to 41.5). Thermal processing times ranged from 76.6min to 90.7min for still retort simulation, from 6.8min to 76.5min for processing with horizontal reciprocating agitation, and from 4.3min to 15.4min for RAM integrated processing. While a significant amount of reduction in thermal process times (up to 91%) was observed for processing with horizontal reciprocating agitation for banana puree samples with a °Bx value between 16.6 and 29.1, this effectiveness dropped sharply (down to 16%) for samples with higher °Bx values (33.2–41.5). For the RAM integrated processing, the applied mixing technology was found to be effective in reducing the thermal process times and provide high quality post-process products throughout the tested range of product viscosities.

Evaluation of resonant acoustic mixing performance

An experimental investigation was carried out to study the mixing performance of a laboratory-scale ResonantAcoustic® Mixer (LabRAM). The first part of the study summarizes the results of a fractional factorial design of experiments used to determine the main effects of process parameters (fill level, acceleration, and blending time) on blend homogeneity. Studies were carried out for several blends having various values of particle size, cohesion and concentration of the active pharmaceutical ingredient. The second part of the study describes the LabRAM mixing performance as a function of process parameters (fill level and acceleration) and total blending time. The blend homogeneity was quantified by estimating the relative standard deviation (RSD) for low concentration of active pharmaceutical ingredient (acetaminophen, 3% w/w) and lubricant (magnesium stearate, 1% w/w) blend. Overall, the LabRAM reached the minimum blend homogeneity in as low as 30s depending on process parameters. The temperature of the final blend increased with fill level, time and acceleration. Resonant acoustic mixing can significantly reduce blending time, making it a good candidate for improving the efficiency of powder mixing processes.

Preparation of an Energetic‐Energetic Cocrystal using Resonant Acoustic Mixing

AbstractResonant acoustic mixing (RAM) was applied to the preparation of an energetic‐energetic cocrystal comprised of CL‐20 and HMX in a 2 : 1 mol ratio. We have prepared the cocrystal using the RAM technology in a resource‐efficient manner providing near quantitative yield. The cocrystalline product from the RAM preparation is consistent with the product from solution crystallization.

Development and Scale-Up of Cocrystals Using Resonant Acoustic Mixing

In the present work resonance acoustic mixing was applied to afford a practical and environmentally friendly approach to produce and scale up cocrystals. Scale-up options for producing cocrystals are limited. Solution-phase cocrystallizations, although amenable to scale-up in stirred tanks, may be limited due to multiple solubility constraints on both coformers and the product cocrystals, resulting in challenges to find feasible processing conditions. While mechanochemical methods such as liquid-assisted grinding (LAG), solid drop grinding (SDG), and ball-milling have been shown to be more general than solution-phase methods, they are also more difficult and impractical to scale up. In the present work a resonant acoustic mixer was used to intimately mix active pharmaceutical ingredient (API) compound and coformer at high frequency, in the presence of a small amount of solvent, to induce conversion to cocrystals with no grinding media required. Carbamazepine (CBZ) and nicotinamide (NCT) were used as a mod...

Pultruded glass fiber- and pultruded carbon fiber-reinforced chemically bonded phosphate ceramics

The main goal of this article is to present the pultrusion process for glass fiber- and carbon fiber-reinforced chemically bonded phosphate ceramics (CBPCs). Samples were fabricated with 15% of fibers by volume. An improvement (with respect to the matrix) of 29 times for the bending strength of CBPCs pultruded graphite fibers composites and 17 times for CBPCs pultruded glass fiber composites is shown. Bending strength was obtained with the three-point bending test. The CBPCs were fabricated by mixing special formulations of both wollastonite powder and phosphoric acid, through resonant acoustic mixing. The microstructure was analyzed with optical and scanning electron microscopes. X-ray compositional maps were obtained for the cross-section of pultruded samples with SEM-EDS. Pultruded sample response at high temperature and thermal shock were also analyzed. The structural characterization of samples was conducted by using X-ray micro tomography.

Chemically bonded phosphate ceramics composites reinforced with graphite nanoplatelets

Chemically bonded phosphate ceramic (CBPCs) composites with 1.0wt.% graphite nanoplatelets (GNPs) reinforcement have been manufactured. The GNPs were functionalized by different procedures, a nitric acid oxidation and a dried oxidation in open air.Two different mixing techniques were used, Thinky and Resonant Acoustic Mixing (RAM). Results showed both techniques are effective to remove most of the air bubbles and a homogeneous distribution of phases was observed with different microscopy techniques.The microstructure was identified by using optical and scanning electron microscopes, X-ray microtomography, and X-ray diffraction (XRD). The bending strength was increased from less than 10MPa (literature) to more than 23MPa. The thermo gravimetric analysis (TGA) technique was used to analyze the thermal stability at high temperature.The main goal in this paper is to enhance the bending strength of the CBPCs reinforced with GNPs, as a substitute composite material for ceramics and cements in structural applications.