Air Jet Mill Research Articles

Effect of Magnesium Stearate and Fines on Delivery of Dry Powder for Inhalation using Sucrose as a Carrier

Typically, lactose is utilised as carrier in Dry Powder Inhaler commercially. However, with the widening scope of DPI in therapeutic categories other than COPD and asthma, a need for the alternate carrier is arising. In this study, we used sucrose, a non-reducing sugar, as an alternate carrier. Effect of addition of fines and magnesium stearate was studied on powder flow properties and aerosolization performance. The air jet milling technique was used to generate sucrose fines. DSC and XRD studies showed no change in sucrose polymorph upon micronization. Levosalbutamol sulphate was used as a model drug, powder blends were prepared by low shear tumbling type blender. Powder formulations were studied for PSD, blend homogeneity, and flow properties. The percentage of particles smaller than 5 microns rose when fines were added as indicated by PSD data. SEM study revealed that the added fines get adsorbs on the coarse carrier, thus minimizing the adhesive interactions between drug and coarse carrier. In-vitro deposition was studied using low and high resistance devices on glass Twin Stage Impinger (TSI). Addition of fines and the magnesium stearate improves aerosolization performance showing higher Fine Particle Fraction (FPF) by almost 2 folds than the formulation containing coarse carrier alone.

The Preparation of an Ultrafine Copper Powder by the Hydrogen Reduction of an Ultrafine Copper Oxide Powder and Reduction Kinetics.

Ultrafine copper powders were prepared by the air-jet milling of copper oxide (CuO) powders and a subsequent hydrogen (H2) reduction. After milling, the particle size and grain size of CuO powders decreased, while the specific surface area and structural microstrain increased, thereby improving the reaction activity. In a pure H2 atmosphere, the process of CuO reduction was conducted in one step, and followed a pseudo-first-order kinetics model. The smaller CuO powders after milling exhibited higher reduction rates and lower activation energies compared with those without milling. Based on the unreacted shrinking core model, the reduction of CuO powders via H2 was controlled by the interface reaction at the early stage, whereas the latter was limited by the diffusion of H2 through the solid product layer. Additionally, the scanning electron microscopy (SEM) indicated that copper powders after H2 reduction presented a spherical-like shape, and the sintering and agglomeration between particles occurred after 300 °C, which led to a moderate increase in particle size. The preparing parameters (at 400 °C for 180 min) were preferred to obtain ultrafine copper powders with an average particle size in the range of 5.43-6.72 μm and an oxygen content of less than 0.2 wt.%.

Solubility Enhancement of Poorly Water-Soluble Aceclofenac by Amalgamation Micronization and Solid Dispersion Techniques

Aceclofenac is a poorly aqueous soluble Biopharmaceutical Classification System (BCS) class II drug that has bioavailability problems after oral administration due to low aqueous solubility. There are numerous solubility modification approaches and they also have process limitations. Hence, the present research work aims to use two different solubility enhancement techniques (Micronization with Solid dispersion) simultaneously to counter individual limitations of techniques. The micronization technique increases the solubility of pure aceclofenac through increasing particle surface area, but it produces charged micronized material, leading to segregation and clumping of micronized material. Hence, micronized material handling during dosage form manufacturing is quite difficult. In the present research work, aceclofenac material is micronized by air jet mill to produce materials of below 25 μm size ranges. This micronized aceclofenac material is further encapsulated in a solid dispersion technique to produce amorphous aceclofenac materials. Solid dispersion of micronized aceclofenac was prepared by various techniques like physical kneading, solvent evaporation, melting and a combination thereof using different polymers (Polyox 301, HPMC, cetostearyl alcohol and glyceryl behenate). The prepared solid dispersion formulation (SD-31, SD-22, SD-23 and SD-30) exhibited an increase in the dissolution of aceclofenac as compared to pure aceclofenac. Various characterization techniques (Differential scanning calorimetry (DSC), X-ray Diffraction (XRD) and scanning electron microscope (SEM)) also reveal that aceclofenac crystallinity is significantly minimized in Solid dispersion formulation of SD-31, SD-22, SD-23 and SD-30. This selected solid dispersion (SD-31 and SD-22) also exhibited good stability (Photostability and stability at 40°C/75% RH after 3 months).

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 ℃ 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.

Characterization of biodegradable corn starch-based foam container incorporating kimchi cabbage (Brassica rapa L. pekinensis) by-product

The production of synthetic plastics, particularly in the food industry, contributes to an increasing number of environmental challenges. This study aimed at developing a corn-starch-based foam (CSBF) container that incorporates kimchi cabbage (Brassica rapa L. pekinensis) by-product (KCB) from the kimchi manufacturing industry. Through alkaline pretreatment (AP) and air jet milling (AJM) of high-moisture KCB, we observed improvements in cellulose content, crystallinity, water-holding capacity, and particle size reduction. The CSBF container produced using KCB powder processed with AP and AJM (KCB-3 powder) showed decreased thickness and increased density compared to the control (CSBF container without KCB-3 powder). Furthermore, the porous microstructure became more compact, enhancing the container's tensile strength and water resistance. The inclusion of KCB-3 powder resulted in a decreased L* value, accompanied by an increase in the a* and b* values of the CSBF containers. However, when the KCB-3 powder content exceeded 20 wt%, cracks formed and mechanical strength degraded. The residual mass values of the CSBF containers incorporated with KCB-3 powder were significantly higher than those of the control during the soil burial period, indicating a slower biodegradation rate. These findings indicate that discarded KCB has the potential to be a material for biodegradable starch-based packaging containers.

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.

Towards Selective Laser Melting of High-Density Tungsten

Selective laser melting (SLM) of tungsten (W) is challenging due to its high melting point and brittleness, resulting in defects including balling phenomenon, porosity and cracks. In this work, high-density crack-free SLM W was fabricated by employing cost-effective powders modified through air jet milling. The influence of the SLM processing parameters on microstructure, density, crack formation and the resulting mechanical properties of SLM W was investigated. Laser energy density and hatch distance were found to be the most important parameters in controlling porosity and crack formation of SLM W. The check-like microstructure in horizontal plane was induced by the difference in thermal gradients, which were caused by the movement of the heat source between overlapping regions and central regions of the molten pool. Combined efforts including powder modification through air jet milling, a 67° rotation scanning strategy, a hatch distance of 0.08 mm and a laser speed of 450 mm/s result in dense crack-free SLM W with relative density of 99.3%, microhardness of 403 HV50, and bending strength of 154 MPa. Additionally, the microstructure changed upon annealing at 1200 °C, accompanied by the reduced anisotropy of mechanical properties on both horizontal and vertical plane.

Enhanced wear resistance of sustainable tire materials with plasma modified pyrolysis carbon black

In this study, pyrolysis carbon black (CBp) was pre-treated by the combination of air jet milling and Ar plasma technology to obtain the reinforcing filler, MP-CBp. The modification effect was verified by XPS, Raman spectroscopy and TEM images. The increment of introduced activation groups and the augmentation of surface area conferred MP-CBp an impressive reinforcement to natural rubber (NR) matrix. The excellent reinforcement of MP-CBp was attributed to the formation of strong filler network according to the mechanical properties. Besides, the tribological studies conducted under various load conditions revealed that the NR component filled with MP-CBp presented intensively improvement on the ground traction and the wear resistance. The addition of 60 phr MP-CBp intensified 20% dry traction, 33.3% wet traction and decreased 27.7% specific wear rate of NR vulcanizates. This strategy to modify CBp with cleanliness Ar plasma technique provides novel insights into not only the surface treatment of CBp, but also the manufacture of sustainable wear-resistant tire materials, which can tremendously promote the recycled utilization of waste tires.

Breakage of a Single Particle in an Air Jet Mill

Breakage of a Single Particle in an Air Jet Mill

All-Gas-Phase Synthesis of Heterolayered Two-Dimensional Nanohybrids Decorated with Metallic Nanocatalysts for Water Splitting.

Herein, a sequential gas-phase process involving air jet milling followed by chemical vapor deposition (CVD), is demonstrated to be an efficient strategy for the fabrication of heterolayered 2D nanohybrids (2DNHs) decorated with nanocatalysts. Tens of grams of the nanohybrids, which is a substantial quantity at the laboratory scale, are produced in the absence of solvents and water, and without the need for an extra purification procedure. Air jet milling enables the development of binary/ternary heterolayered structures consisting of graphene, WSe2 , and/or MoS2 via the gas-phase co-exfoliation of their bulk counterparts. Based on the X-ray photoelectron and Raman spectroscopy data, the heterolayers of the 2DNHs exert chemical and electronic effects on each other, while diminishing the interactions between same-component layers. Moreover, the electrochemically active surface area increases by >190% and the charge transfer resistance decreases by >35%. CVD is performed to introduce Pt and Ru nanoparticles with diameters of a few nanometers as additional electrocatalysts into the 2DNHs. The nanocatalyst-decorated 2DNHs show excellent performance for the production of hydrogen and oxygen gases in water-splitting cells. Notably, the proposed all-gas-phase processes allow for the large-scale production of functional 2DNHs with minimal negative environmental impact, which is crucial for the commercialization of nanomaterials.

Correlation between milling-induced strain, microstructure, and magnetic properties in anisotropic SrFe12O19 powders

Strontium hexaferrite (SrFe12O19) powders synthesized via conventional solid-state route are mechanically milled using air jet-mill and ball-mill techniques to produce anisotropic SrFe12O19 powders. Jet-milled and dry ball-milled powders showed higher strain (0.13%) compared to wet ball-milled powders (0.05%). On annealing, jet-milled powder exhibited better recovery of strain compared to the ball-milled powders. Enhancement in coercivity after annealing is maximum in jet-milled samples (1.7 kOe to 5.2 kOe). Angle-dependent magnetic hysteresis measurements suggest a difference in the nature of strain induced in jet-mill and ball-mill methods. Maximum remanence (0.81) is observed in both jet-milled and dry ball-milled powders, however, jet-milled powders showed a better retention of remanence (0.74) after annealing than the ball-milled powders (0.64). A stark contrast in the microstructure of jet-milled and ball-milled powders is revealed from SEM images. Particle size distribution curves confirm a considerable re-agglomeration in the ball-milled samples. The role of milling-induced strain and microstructure in obtaining anisotropic SrFe12O19 powders with optimum remanence and coercivity is discussed.

Analysis of grinding in a spiral jet mill. Part 2: Semi-batch grinding

The breakage and classification of particles in a spiral air jet mill, operated in a semi-batch mode, is studied for varying operating conditions. The particle size distributions of the product leaving the mill and the material inside the mill are measured, along with the mass in the mill. The median particle size of the product is found to be unchanged with inlet jet pressure at about 5 μm but increases with holdup to about 7.5 μm. At low pressures and high holdups, the classification is imperfect and a significant fraction of large particles, in the size range 150–350 μm, exit in the product. The mass flux from the mill increases with both pressure and holdup and an empirical expression is given to calculate it. A population balance model is presented, which predicts size distributions, mean sizes and mass flux from the mill, in agreement with the measurements.

Understanding Poor Milling Behavior of Voriconazole from Crystal Structure and Intermolecular Interactions

The study investigated the milling behavior of voriconazole (VRZ) subjected to particle size reduction using air jet mill at differential air pressures of 5, 6, 7, and 8 bar for five cycles at each pressure. The crystal structure of VRZ was probed for understanding the fracture behavior from crystal packing and intermolecular interactions using molecular modeling tools of attachment energy (Eatt), density functional theory, and energy framework analysis. Upon milling for different cycles, VRZ showed that size reduction from (D90) 20 to 9 μm and 100% particles could not be milled to sizes below 9 μm, with the increase in either the milling intensity or cycle. The milled samples retained the original crystal lattice as evident from consistent melting endotherm (Tm = 130.75 °C); heat of fusion (ΔHf = 96.52 J/g) values; and the plate-shaped morphology. The powder X-ray diffraction pattern of milled samples consistently showed characteristic peaks of stable form B of VRZ. The crystallographic plane (001) was found to be the most prominent slip and the cleavage plane due to least Eatt and weak noncovalent interactions (6.996 kJ/mol) between 3'H and 4'F functional groups of the neighboring planes. The predicted indentation hardness value of 228.67 MPa further indicated toward the plastic nature of VRZ crystals. Corroborating outcomes from the different molecular modeling tools for VRZ, cleavage along the plane (001) was determined to be energetically favorable, whereas cleavage of isotropic 2D molecular sheets was energetically unfavorable. As milling proceeds and crystal reduces in size, contact surface area and overall interaction energy decrease contributing to plastic behavior of the crystal. It was concluded that crystal plasticity and isotropic 2D molecular sheets along with the orientation of particles to the direction of stress and attrition energy during air jet milling are contributing factors for nonuniform size reduction of VRZ particles.

Influence of nozzle angle and classifier height on the performance of a spiral air jet mill

We study the effect of varying air jet mill design parameters, the nozzle angle and the classifier tube height, on the performance of the mill, operated in the semi-batch mode, using quartz and limestone particles as feed. Particle size distributions of the product and the material in the mill are measured along with the mass in the mill. The product size distribution and the specific mass flux are found to be constant with time. The breakage rate is found to increase with nozzle angle. The efficiency of classification, characterized by the fraction of coarse particles larger than the cut size, increases with nozzle angle and classifier tube height. The energy for grinding per unit mass of the product decreases with nozzle angle and increases with classifier tube height and optimal values of the parameters, at which the specific energy is minimized, are obtained.

The Influence of Relative Humidity and Storage Conditions on the Physico-chemical Properties of Inhalation Grade Fine Lactose.

Dry powder inhalers (DPIs) are favorable devices for the delivery of dry formulations to the lungs; still, they largely fail to deliver higher doses of active pharmaceutical ingredient (API) to the lower airways. Addition of fine particles of excipient (fines) to the blend of API and carrier was shown to improve aerosolization performance. Lactose monohydrate is ubiquitous excipient used for this purpose. Lactose exists in a thermodynamically stable crystalline form; however, processes like milling, sieving, or even mixing may induce alteration of crystalline structure and introduce amorphous domains, which could further affect the physico-chemical properties of the material. Therefore, the aim of this work is a detailed characterization of two commercially available types of inhalation grade fine lactose powders (Inhalac 400 and Inhalac 500) prepared using different air-jet milling parameters, with a focus on impact of storage conditions on material properties. We found that the different milling parameters resulted in variable particle size distribution (PSD), and thus surface areas, variable initial amorphous content, cohesivity, flowability, and moisture sorption of materials. In addition, exposure of fine powders to higher humidity reduced the amorphous content present in the materials, but also affected agglomeration tendency and dispersion behavior of both powders. We believe the obtained findings to be important for the aerosolization performance of carrier-based DPIs containing fines and thus need to be duly considered during formulation development.

Utilizing Solid-State Techniques and Accelerated Conditions to Understand Particle Size Instability in Inhaled Drug Substances.

Micronization by air jet milling is often used to produce drug substance particles of acceptable respirable size for use in dry powder inhaler formulations. The energy from this process often induces surface disordered sites on the micronized particles with potential consequences for the long-term stability of the drug substance. In this study, two lots of the same drug substance were qualitatively determined to have different extents of disordered surface using dynamic vapor sorption and scanning electron microscopy. These differences led to observable divergences in particle size and morphology between lots of drug substances on long-term and accelerated stability. The studies investigate the contribution of temperature and humidity, morphology prior to milling, and stability behavior post-micronization. The results highlight the importance of controlling the crystallization solvents upstream of micronization and their contribution to a material's susceptibility to milling-induced disorder on long-term physical stability. Furthermore, this work proposes an accelerated technique useful in predicting stability behavior of micronized drug substances in days rather than months, especially in cases where small differences cannot be detected by standard solid-state techniques.

Role of surface molecular environment and amorphous content in moisture sorption behavior of milled Terbutaline Sulphate

Milling may cause undesired changes in crystal topology, due to exposure of new facets, their corresponding functional groups and surface amorphization. This study investigated effect of milling induced surface amorphous content and chemical environment on moisture sorption behavior of a model hydrophilic drug, Terbutaline Sulphate (TBS). A Dynamic Vapor Sorption (DVS) based analytical method was developed to detect amorphous content, with LOD and LOQ of 0.41% and 1.24%w/w, respectively. The calibration curve gave a linear regression of 0.999 in a concentration range of 0-16.36%w/w amorphous content plotted against surface area normalized % weight change, due to moisture sorption. TBS was milled using air jet mill at 8 Bars for 3 cycles (D90- 3.46µm) and analyzed using the validated DVS method prior to and post conditioning. The moisture sorption was higher in case of milled unconditioned TBS.Molecular Dynamics Simulation (MDS) was performed to identify the cause for increased moisture sorption due to altered surface environment or amorphous content. The results implied that the new planes and functional groups exposed on milling had negligible contribution to moisture sorption and the higher moisture sorption in milled unconditioned TBS was due to surface amorphization. Conditioning under elevated humidity recrystallized the milling-induced surface amorphous content and led to decreased moisture sorption in milled conditioned TBS.

Assessment of the parameter identifiability of population balance models for air jet mills

Air jet mills are ubiquitous breakage devices not only in the pharmaceutical industry, but also in food and the toner manufacturing industry. The popularity of air jet mills arises due to its self-classifying, non-contaminating, and non-degrading operation while also maintaining a narrow particle size distribution. A popular approach towards mathematically modelling comminution devices like the jet mill is the population balance model framework. Population balance model for breakage is a semi-empirical framework in which several parameters are estimated from the experimental data. In many cases the experimental data available is insufficient, or of bad quality to guarantee the estimation of unique parameters. Thus it is imperative to assess the identifiability of such models to ensure that the chosen model structure is identifiable, both structurally and practically. In this study, we analyse the identifiability of the population balance model developed for the air jet mill. The identifiability analysis is carried out on basis of in-silico data generated by assuming certain parameter values to represent the true process. Based on several scenarios tested with data containing variety of information, it is shown that the model is practically non-identifiable for the situations in which the particle size measurement is available only at the end of the milling. The model becomes identifiable once continuous time measurements are available. The same holds for a reduced model with only the five breakage parameters.

Development and demonstration of a semi-automatic system for the bulk production of lithium titanate (Li2TiO3) pebbles by solid state reaction process (SSRP)

Abstract Lithium titanate ( L i 2 T i O 3 ) has been selected as ceramic solid tritium breeding materials for the ITER Test Blanket Module (TBM) and also for DEMO reactor. Looking towards its future demand in large quantities, it is necessary to develop a system for bulk production of the lithium titanate pebbles. A semi-automatic system for the bulk production of lithium titanate (Li2TiO3) pebbles by Solid-State Reaction Process (SSRP) has been designed, developed and successfully demonstrated. Raw materials; viz. lithium carbonate ( L i 2 C O 3 ) and titanium dioxide ( T i O 2 ) were mixed in required stoichiometry and fed into the continuous rotary synthesizer. L i 2 T i O 3 powder was synthesized in a continuous rotary synthesizer at 10 kg/h production capacity. This synthesized powder was milled in air jet mill. Milled powder was fed into the extrusion-spheronization based automated granulation system and green, spherical L i 2 T i O 3 pebbles of were produced at the production rate of 25 kg/h. Green spherical pebbles were dried, classified and sintered It was found that the synthesized L i 2 T i O 3 was in monoclinic β- L i 2 T i O 3 phase according to JCPDS No. 33-0831 and the properties of the sintered Li2TiO3 pebbles were well within the desired values. The process and various process parameters are discussed in details in this paper.

Development of an Excipient-Free Peptide Dry Powder Inhalation for the Treatment of Pulmonary Fibrosis.

The caveolin scaffolding domain peptide (CSP) is being developed for the therapeutic intervention of a lethal lung disease, idiopathic pulmonary fibrosis. While direct respiratory delivery of CSP7 (a 7-mer fragment of CSP) is considered an effective route, proper formulation and processing of the peptide are required. First, air-jet milling technology was performed in order to micronize the neat peptide powder. Next, the fine particles were subjected to a stability study with physical and chemical characterizations. In addition, the in vivo efficacy of processed CSP7 powder was evaluated in an animal model of lung fibrosis. The results revealed that, with jet milling, the particle size of CSP7 was reduced to a mass median aerodynamic diameter of 1.58 ± 0.1 μm and 93.3 ± 3.3% fine particle fraction, optimal for deep lung delivery. A statistically significant reduction of collagen was observed in diseased lung tissues of mice that received CSP7 powder for inhalation. The particles remained chemically and physically stable after micronization and during storage. This work demonstrated that jet milling is effective in the manufacturing of a stable, excipient-free CSP7 inhalation powder for the treatment of pulmonary fibrosis.