The Effects of Jet-Milling and Pulsed Electric Fields on the Preservation of Spinach Juice Lutein Contents during Storage.

This study aimed to investigate the effects of jet-milling on the lutein extraction contents of spinach powder (SP), as well as the effects of pulsed electric field (PEF), as a non-thermal pasteurization technology, on the preservation of spinach juice (SJ) lutein contents. SP particles were divided into SP-coarse (Dv50 = 315.2 µm), SP-fine (Dv50 = 125.20 µm), and SP-superfine (Dv50 = 5.59 µm) fractions, and SP-superfine was added to SJ due to its having the highest contents of lutein extract. PEFs and thermal treatment were applied to evaluate the effects of preserving the lutein content of PEF during storage (25 days). The juice was then designated as untreated (no pasteurization), PEF-1,2 (SJ treated with PEF 20 kV/cm 110 kJ/L, 150 kJ/L), or Thermal-1,2 (SJ treated with 90 °C, 10 min and 121 °C, 15 min). The sizes and surface shapes of the superfine SP particles were more homogeneous and smoother than those of the other samples. SJ made with SP-superfine and treated with PEF had the highest lutein content and antioxidant activities among the group during storage. A complex of jet-milling and PEF could have great potential as a method to improve the lutein contents of lutein-enriched juice in the food industry.

Enhanced green remediation and refinement disposal of electrolytic manganese residue using air-jet milling and horizontal-shaking leaching.

The reclamation and reuse of electrolytic manganese residue (EMR) as a bulk hazard solid waste are limited by its residual ammonia nitrogen (NH4+-N) and manganese (Mn2+). This work adopts a co-processing strategy comprising air-jet milling (AJM) and horizontal-shaking leaching (HSL) for refining and leaching disposal of NH4+-N and Mn2+ in EMR. Results indicate that the co-use of AJM and HSL could significantly enhance the leaching of NH4+-N and Mn2+ in EMR. Under optimal milling conditions (50 Hz frequency, 10 min milling time, 12 h oscillation time, 400 rpm rate, 30 â„ƒ temperature, and solid-to-liquid ratio of 1:30), NH4+-N and Mn2+ leaching efficiencies were optimized to 96.73% and 97.35%, respectively, while the fineness of EMR was refined to 1.78 µm. The leaching efficiencies of NH4+-N and Mn2+ were 58.83% and 46.96% higher than those attained without AJM processing. The AJM used strong airflow to give necessary kinetic energy to EMR particles, which then collided and sifted to become refined particles. The AJM disposal converted kinetic energy into heat energy upon particle collisions, causing EMR phase transformation, and particularly hydrated sulfate dehydration. The work provides a fire-new and high-efficiency method for significantly and simply leaching NH4+-N and Mn2+ from EMR.

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 µM and >0.5 µM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

Comparative study of encapsulated cannabidiol ternary solid dispersions prepared by different techniques: The application of a novel technique jet milling.

Jet milling is a common technique in ultrafine powder preparation field. It has never been used to design delivery systems. Cannabidiol (CBD) is an important cannabinoid of hemp but poor aqueous solubility limited its applications. In this study, solid dispersion (SD) technique was combined with cyclodextrin complexation technique, and jet milling was used for the first time to prepare SDs for improving CBD solubility. Different characterizations demonstrated that the dispersion effect and complexation structure of CBD SD3 prepared by jet milling were comparable to that of CBD SD2 prepared by spray drying (a common solution-based method), and were better than that of CBD SD1 prepared by cogrinding. The water solubility of CBD was increased to 20.902 µg/mL (909-fold) in CBD SD3. Besides, the antioxidant activity and cytotoxicity to tumor cells of CBD were enhanced by dispersion. This work indicated that jet milling, as a new technique with low cost and excellent applicability, could be further developed for the delivery of food functional factors or bioactive molecules.

A facile one-step jet-milling approach for the preparation of proliposomal dry powder for inhalation as effective delivery system for anti-TB therapeutics.

OBJECTIVE: Physicochemical characterization and assessment of aerosol dispersion performance of anti-TB proliposome dry powders for inhalation (DPIs) prepared using a single-step jet-milling (JM) approach. SIGNIFICANCE: Conventional tuberculosis (TB) treatment involves isoniazid and rifampicin as first-line agents in extended oral multi-drug regimes. Liposomal DPIs are emerging as promising alternatives for targeted delivery of anti-TB agents to alveolar macrophages harboring Mycobacterium tuberculosis. However, traditional approaches for liposomal DPI preparation are tedious, time consuming and require sophisticated/expensive equipment. The proposed JM technique for preparation of proliposome DPIs could obviate these limitations and facilitate use of these drugs for more effective and safer treatment. METHODS: Proliposome DPIs containing isoniazid and/or rifampicin, cholesterol and cholesterol sulfate were successfully prepared via JM (injection pressure, 7.4 bar; milling pressure, 3.68 bar). Their physicochemical, content uniformity, and in vitro aerosol dispersion performance were assessed using scanning electron microscopy/energy-dispersive X-ray spectroscopy, transmission electron microscopy, dynamic light scattering/Zeta potential, X-ray diffraction spectroscopy, thermogravimetric analysis, high-performance liquid chromatography, and the Next-Generation Impactor. RESULTS: The DPIs exhibited consistent, spherically shaped, smooth particles. Drug particles were evenly distributed with acceptable content uniformity. Drug crystallinity was not significantly affected by milling and the formulations had minimal (<2.0%) water content. After reconstitution of the DPIs, the hydrodynamic size was about 370.9-556.2 nm and charge was -12.3 to -47.3 mV. Furthermore, the proliposome DPIs presented emitted dose (69.04-89.03%), fine particle fraction, <4.4 µm (13.7 - 57.8%), and mass median aerodynamic diameter (<3.0 µm), which satisfied the requirements for deep lung delivery. CONCLUSION: The proposed approach was suitable for preparation of proliposome DPIs that could be deployed for local targeting of the lower respiratory tract for the treatment of TB.

Effects of Jet Milling on the Physicochemical Properties of Buckwheat Flour and the Quality Characteristics of Extruded Whole Buckwheat Noodles.

The effects of jet milling on the physicochemical properties of buckwheat flour and the quality characteristics of extruded whole buckwheat noodles (WBN) were investigated in this study. The results reveal that the application of jet milling significantly reduced the particle size of buckwheat flour. As a result, the damaged starch content, water solubility index, water absorption index and swelling power of buckwheat flour all increased. It was worth noting that moderately ground buckwheat flour powder (D50 = 65.86 µm) had the highest pasting viscosity and gel hardness. The breaking rate and cooking loss of extruded whole buckwheat noodles made from the above powder were reduced by 33% and 16%, respectively. Meanwhile, they possessed the highest lightness and firmest network structure. Jet milling increased the soluble dietary fiber (SDF) content from 3.45% to 4.39%, and SDF further increased to 5.28% after noodle extrusion. This study was expected to provide a reference for exploiting high-quality gluten-free noodles from the perspective of milling.

Effects of Jet Milling Pretreatment and Esterification with Octenyl Succinic Anhydride on Physicochemical Properties of Corn Starch.

(1) Background: In this study, aiming at the problems of low efficiency and high energy consumption in the esterification reaction of OSA and starch, the jet milling technology was used to pretreat corn starch and starch raw materials with different pulverization strengths were obtained by controlling the speed of the classifier. (2) Methods: The starch obtained under different classification speeds was modified by esterification with OSA. Using CLSM, FTIR, XRD, NMR, FTIR, XPS, and other technologies, the modification effect was verified, and the physical and chemical properties of J-OSA-Starch such as DSC, RVA, transparency, and emulsifying properties were determined. (3) Results: Jet milling pretreatment significantly reduced the particle size of corn starch and improved the reaction efficiency and degree of substitution during esterification with OSA. After pretreatment, the corn starch granules were broken, and the relative crystallinity was significantly reduced. CLSM, FTIR, XPS, and NMR confirmed the esterification of corn starch with OSA, which increased with increasing crushing strength. The thermodynamic properties and viscosity of J-OSA-starch decreased with the increase in the classification speed. Jet milling pretreatment enhanced the clarity, emulsifying activity, and emulsifying stability of OSA-modified corn starch. (4) Conclusions: Jet milling pretreatment can effectively increase the esterification efficiency of starch and OSA. Therefore, jet milling can be used as a pretreatment to improve the esterification of starch OSA and produce modified starch for industrial applications.

Remdesivir powders manufactured by jet milling for potential pulmonary treatment of COVID-19.

Remdesivir is one of the effective drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, the study on inhalable regimen is currently limited though COVID-19 is respiratory diseases and infects lung area. This work aims to prepare inhalable remdesivir formulations and verify their effectiveness through in vitro evaluations. Formulations containing different ratios of jet-milled inhalable remdesivir (5, 10, 20,40, and 70%) with excipients were produced and characterized in terms of the particle size distribution, particle morphology, flowability, water content, crystallinity, the water sorption and desorption capabilities, and the aerodynamic performance. Results indicating that drug loading are a vital factor in facilitating the dispersion of remdesivir dry powder, and the ternary excipient plays a negligible role in improving aerosol performance. Besides, the 70% remdesivir with lactose carrier (70% RD-Lac) was physically stable and retain high aerosol performance after conditioned at 40 °C and 75% RH for a month. Therefore, formulation 70% RD-Lac might be recommended as a candidate product for the potential treatment of COVID-19.

W-Cu Composite with High W Content Prepared by Grading Rounded W Powder with Narrow Particle Size Distribution.

In this study, the W (10-20%)-Cu composites were simultaneously fabricated using commercial, graded commercial, and graded jet-milled W powder. The results show that the W-Cu composites prepared with the graded jet-milled W powders have the highest density and best comprehensive performance due to the combined effect of the particle gradation and jet-milling treatment. Particle gradation is employed to increase the packing density of powders, thereby increasing the relative density of the compressed W skeleton, and the rounded powder with narrow particle size distribution after jet-milling treatment is used to reduce the enclosed pores formed during the process of compacting and infiltration. W-Cu composites with a high density of 16.25 g/cm3 can be directly obtained by conventional compacting at a low pressure of 300 MPa and following infiltration.

Novel Colloidal Dispersing Concept in Aqueous Media for Preparation by Wet-Jet Milling Dispersing Method.

Dispersing particles in a liquid phase is significant for producing various functional nano/bio applications. The wet-jet milling method has been gaining attention as an attractive dispersing method in the preparation of soft material suspensions. This is because the main driving force of dispersion by the wet-jet milling method is the shear force, which is weaker than that it is in the ultrasonication dispersing method. In the wet-jet milling method, the pressure of the narrow channel which the liquid is passes through and the number of passes are used as the control parameters for dispersing the particles. However, the values of the pressure depend on the size (diameter and length) of the narrow channel, thus, it is not a commonly used dispersing parameter in dispersing by wet-jet milling to set the dispersing condition by various wet-jet milling instruments. In addition, wet-jet milling users must optimize the dispersing conditions such as the pressure and number of passes in the narrow channel, therefore, a simple prediction/optimization method of the dispersing size by the wet-jet milling method is desired. In this study, we established a novel colloidal dispersing concept, the dispersing energy input based on a calorimetric idea, for particle suspension preparation using the wet-jet milling method. The dispersing energy input by wet-jet milling was quantitatively calculated under various conditions during the dispersing by wet-jet milling, and then, the dispersing size of the particles was easily predicted/optimized. We demonstrated the usability of the concept by preparing aqueous suspensions of calcium carbonate (CaCO3) particles with various surfactants using the wet-jet milling method. Based on the established concept, in a case study on dispersing CaCO3, we found that changes in the micelle sizes of the surfactants played a role in wet-jet milling. The novel idea of the representation of energy input makes it possible to estimate the appropriate condition of the dispersing process by wet-jet milling to control the size of particles.

Fluidized Bed Jet Milling Process Optimized for Mass and Particle Size with a Fuzzy Logic Approach.

The milling process is a complex phenomenon dependent on various technological and material parameters. The development of a fluidized bed jet milling model is of high practical significance, since milling is utilized in many industries, and its complexity is still not sufficiently recognized. Therefore, this research aims to optimize fluidized bed jet milling with the use of fuzzy logic (FL) based approach as one of the primary artificial intelligence (AI) methods. The developed fuzzy logic model (FLMill) of the investigated process allows it to be described as a non-iterative procedure, over a wide range of operating conditions. Working air pressure, rotational speed of the classifier rotor, and time of conducting the test are considered as inputs, while mass and mean Sauter diameter of the product are defined as outputs. Several triangular and constant linguistic terms are used in the developed FLMill model, which was validated against the experimental data. The optimum working air pressure and the test's conducting time are 500 kPa and 3000 s, respectively. The optimum rotational speed of the classifier is equal to 50 s-1, considering the mass of the grinding product, and 250 s-1 for the mean Sauter diameter of the product. Such operating parameters allow obtaining 243.3 g of grinding product with the mean Sauter diameter of 11 µm. The research proved that the use of fuzzy logic modeling as a computer-based technique of solving mechanical engineering problems allows effective optimization of the fluidized bed jet milling process.

Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants.

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.

Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.

Homogeneous mixing of 2 cohesive jet-milled drug powders is a challenge for pharmaceutical manufacturing on account of their cohesive nature resulting in the formation of strong and random agglomerates. In this study, colistin and ciprofloxacin were co-jet milled to develop combinational antibiotic dry powder formulations for inhalation. The properties of particle size, morphology, content uniformity, and in vitro aerosolization were evaluated. The distribution of 2 drugs in the co-jet milled powders was assessed using time-of-flight-secondary ion mass spectrometry. The co-jet milled powders demonstrated an acceptable content uniformity indicating homogeneity. In general, time-of-flight-secondary ion mass spectrometry images showed relatively homogeneous distributions of ciprofloxacin and colistin in the co-milled formulations. Importantly, the 2 drugs generally had the similar fine particle fraction and deposition behavior in each combinational formulation supporting that the particle mixtures were relatively homogenous and could maximize the antimicrobial synergy. In conclusion, co-jet milling could be a viable technique to produce the combination powders for inhalation.

Jet milling industrialization of sticky active pharmaceutical ingredient using quality-by-design approach.

Jet milling is frequently used in pharmaceutical industry to achieve different objectives. It can be used as enabling technology to overcome poor water solubility linked to hydrophobic active of pharmaceutical ingredient (API) by reducing the particle size and therefore increasing the dissolution rate. Alternatively, jet milling can be used either to enhance blending efficiency of API with excipient in case of formulation at low dosage strength or to achieve the required particle size for inhalation therapy. In this study, development of commercial manufacturing process of sticky API and its industrialization are described. The methodology used is based on quality-by-design approach to deliver safe, effective and robust manufacturing process. The study showed that the specific energy is a key factor that drives particle size during jet milling and the scale-up from lab to industrial scale. After understanding the process, a design space was built where different zones such as operating point, operating space (where the product is compliant to specification despite variability of process parameters), and the knowledge space were outlined. Finally, an industrial installation was proposed to deliver product with high productivity yield, compliant with safety regulation, and cleanable in place.

Effect of jet milling on the physicochemical properties, pasting properties, and in vitro starch digestibility of germinated brown rice flour.

Germinated brown rice (GBR) flours were prepared by hammer milling and jet milling. The effect of the milling on the physicochemical and pasting properties of the resultant flours were investigated. The jet milling of GBR resulted in flour with different particle sizes, which were air-classified into coarse and fine size fractions. As the particle size decreased, the amount of damaged starch increased. The WAI, WSI, and oil absorption of the jet-milled GBR flour was slightly lower than that of the hammer-milled flour. Increased α- and ß-amylase activities were observed in the coarse fraction of the jet-milled GBR flour compared with the hammer-milled and jet-milled fine fractions. The RVA viscosity profiles of the fine fraction of the jet-milled GBR flour were significantly higher than those of the hammer-milled or the coarse fraction of the jet-milled GBR flour. Compared with the hammer-milled flour, jet milling increased in vitro starch hydrolysis.

Flexible Graphene/Carbon Nanotube Electrochemical Double-Layer Capacitors with Ultrahigh Areal Performance.

The fabrication of electrochemical double-layer capacitors (EDLCs) with high areal capacitance relies on the use of elevated mass loadings of highly porous active materials. Herein, we demonstrate a high-throughput manufacturing of graphene/carbon nanotubes hybrid EDLCs. The wet-jet milling (WJM) method is exploited to exfoliate the graphite into single-few-layer graphene flakes (WJM-G) in industrial volumes (production rate ca. 0.5 kg/day). Commercial single-/double-walled carbon nanotubes (SDWCNTs) are mixed with graphene flakes in order to act as spacers between the flakes during their film formation. The WJM-G/SDWCNTs films are obtained by one-step vacuum filtration of the material dispersions, resulting in self-standing, metal- and binder-free flexible EDLC electrodes with high active material mass loadings up to around 30 mg cm-2 . The corresponding symmetric WJM-G/SDWCNTs EDLCs exhibit electrode energy densities of 539 µWh cm-2 at 1.3 mW cm-2 and operating power densities up to 532 mW cm-2 (outperforming most of the reported EDLC technologies). The EDCLs show excellent cycling stability and outstanding flexibility even in highly folded states (up to 180°).

Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration.

Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy.

WS2-Graphite Dual-Ion Batteries.

A novel WS2-graphite dual-ion battery (DIB) is developed by combining a conventional graphite cathode and a high-capacity few-layer WS2-flake anode. The WS2 flakes are produced by exploiting wet-jet milling (WJM) exfoliation, which allows large-scale and free-material loss production (i.e., volume up to 8 L h-1 at concentration of 10 g L-1 and exfoliation yield of 100%) of few-layer WS2 flakes in dispersion. The WS2 anodes enable DIBs, based on hexafluorophosphate (PF6-) and lithium (Li+) ions, to achieve charge-specific capacities of 457, 438, 421, 403, 295, and 169 mAh g-1 at current rates of 0.1, 0.2, 0.3, 0.4, 0.8, and 1.0 A g-1, respectively, outperforming conventional DIBs. The WS2-based DIBs operate in the 0 to 4 V cell voltage range, thus extending the operating voltage window of conventional WS2-based Li-ion batteries (LIBs). These results demonstrate a new route toward the exploitation of WS2, and possibly other transition-metal dichalcogenides, for the development of next-generation energy-storage devices.

Process optimization and particle engineering of micronized drug powders via milling.

Process control and optimization is a critical aspect of process analytical technology (PAT), quality by design (QbD), and the implementation of continuous manufacturing procedures. While process control and optimization techniques have been utilized in other manufacturing industries for decades, the pharmaceutical industry has only recently begun to adopt these procedures. Micronization, particularly milling, is a generally low-yield, high-energy consumption process that is well suited for a process optimization mindset. This review discusses optimization of the pharmaceutical milling process through design space development, theoretical and empirical modeling, and monitoring of critical quality attributes.

Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air Jet Micronization.

Clofazimine (CFZ) is highly active against mycobacterium, including resistant Mycobacterium tuberculosis, but its therapeutic efficacy via the oral route is limited by severe adverse effects, poor aqueous solubility, and slow onset of action. Pulmonary delivery of CFZ is an attractive alternative to target mycobacterium-harboring alveolar macrophages. This study explores the use of air jet milling to develop a respirable, cost-effective CFZ formulation. Jet milled CFZ was readily dispersed from an off-the-shelf dry powder inhaler without the need for additional excipients or carrier particles. Additionally, milled CFZ was internalized by J774.A1 alveolar macrophages within 8 h, with evidence of intracellular biotransformation of the CFZ crystals and macrophage sequestration by 24 h. Less macrophage toxicity was noted in comparison to solubilized drug. Compared to macrophage uptake rate, dissolution of milled CFZ was limited, thereby potentially reducing systemic absorption and subsequent side effects. These results suggest that jet milling is an effective manufacturing method in the development of a CFZ formulation for pulmonary delivery and alveolar macrophage targeting.