Atomization Gas Flow Rate Research Articles

Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process. Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained. The products exhibited fast drug release due to preserved self-microemulsifying properties and the absence of crystalline carvedilol, which was confirmed with XRD and Raman mapping. A decrease in drug content during the stability study was observed and investigated. This was at least partially attributed to the chemical degradation of the drug. Key degradation products determined by the LC-MS method were amides formed by in situ reaction of carvedilol with fatty acids present in the oily phase of SMEDDS.

Working Mechanism and Behavior of Collison Nebulizer

The Collison nebulizer (as well as its variations) has been widely used for generating fine aerosol droplets of a few microns from liquids of viscosity up to 1000 centipoise. It was originally developed for producing medical aerosols in inhalation therapy, and now has become an important component as pneumatic atomizer in the Aerosol Jet(R) direct-write system for additive manufacturing. Qualitative descriptions of its working mechanism were given in the literature as an expanding high-speed gas jet creates a negative pressure to syphon liquid into the jet stream, where the liquid is subsequently blown into sheets, filaments, and eventually droplets. But quantitative analysis and in-depth understanding have been lacking until rather recently. In this work, we present a logical description of the working mechanism of Collison nebulizer based on OpenFOAM(R) CFD analysis of compressible jet flow in the jet expansion channel. The positive-feedback liquid aspiration mechanism becomes clear by examining the CFD results as the jet expansion channel geometry is varied. As a consequence, the output mist density can be rather insensitive to the liquid viscosity, which is illustrated by a set of experiments with the Collison-type pneumatic atomizer in an Aerosol Jet(R) direct-write system. Thus, an intrinsic self-regulation mechanism is elegantly incorporated in the Collison nebulizer design. As intuitively expected, experimental data also supports the notion of the existence of an upper limit for liquid holdup in the limited space of jet expansion channel; therefore, the output mist density cannot increase indefinitely by increasing the atomization gas flow rate.

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient.

The prospect of inhaled biologics has garnered particular interest given the benefits of the pulmonary route of administration. Pertinent considerations in producing inhalable dry powders containing biological medicines relate to aerosol performance and protein stability. Spray-freeze-drying (SFD) has emerged as an established method to generate microparticles that can potentially be deposited in the lungs. Here, the SFD conditions and formulation composition were evaluated using bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as the protein stabilizer. A factorial design analysis was performed to investigate the effects of BSA content, solute concentration of feed solution, and atomization gas flow rate on dispersibility (as an emitted fraction), respirability (as fine particle fraction), particle size, and level of protein aggregation. The atomization gas flow rate was identified as a significant factor in influencing the aerosol performance of the powder formulations and protein aggregation. Nonetheless, high atomization gas flow rate induced aggregation, highlighting the need to further optimize the formulation. Of note, all the formulations exhibited excellent dispersibility, while no fragmentation of BSA occurred, indicating the feasibility of SFD and the promise of HPβCD as an excipient.

Microencapsulation of Copper(II) Sulfate in Ionically Cross-Linked Chitosan by Spray Drying for the Development of Irreversible Moisture Indicators in Paper Packaging.

Copper(II) sulfate-loaded chitosan microparticles were herein prepared using ionic cross-linking with sodium tripolyphosphate (STPP) followed by spray drying. The microencapsulation process was optimal using an inlet temperature of 180 °C, a liquid flow-rate of 290 mL/h, an aspiration rate of 90%, and an atomizing gas flow-rate of 667 nL/h. Chitosan particles containing copper(II) sulfate of approximately 4 µm with a shrunken-type morphology were efficiently attained and, thereafter, fixated on a paper substrate either via cross-linking with STPP or using a chitosan hydrogel. The latter method led to the most promising system since it was performed at milder conditions and the original paper quality was preserved. The developed cellulose substrates were reduced and then exposed to different humidity conditions and characterized using colorimetric measurements in order to ascertain their potential as irreversible indicators for moisture detection. The results showed that the papers coated with the copper(II) sulfate-containing chitosan microparticles were successfully able to detect ambient moisture shown by the color changes of the coatings from dark brown to blue, which can be easily seen with the naked eye. Furthermore, the chitosan microparticles yielded no cytotoxicity in an in vitro cell culture experiment. Therefore, the cellulose substrates herein developed hold great promise in paper packaging as on-package colorimetric indicators for monitoring moisture in real time.

Determination of Fe in Graphene by Inductively Coupled Plasma Optical Emission Spectrometer

The Fe in graphene was determined by inductively coupled plasma optical emission spectroscopy. The effects of digestion temperature, digestion system, analyzing spectral line, RF power, peristaltic pump flow rate, and working gas flow rate on the measurement results were investigated respectively. The results show that the best digestion effect appear when the digestion temperature is 550 °C and the digestion system is 3ml hydrochloric acid combined with 1ml nitric acid. The most stable and reliable test results obtained when the analyzing spectral line is 259.941 nm, the RF power is 1400W, the peristaltic pump flow rate is 50r/min, the atomizing gas flow rate is 0.8L/min, and the auxiliary gas flow rate is 1.0L/min. The detection limit of the measurement result is 0.029mg/L, the relative standard deviation (n=6) is between 2.5% and 3.2%, and the recovery is between 96.3% and 108.2%.

Analysis of chemical components of Huanbei Zhike Prescription based on UPLC-Q-TOF-MS/MS technology

To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 μm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 μL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.

Simultaneous determination of six kinds of components in Buyang-Huanwu decoction by UHPLC-MS/MS

Objective To develop the UHPLC-MS/MS method for the determination of amygdalin, paeoniflorin, ferulic acid, calycosin glucosidase, quercetin and formononetin in Buyang-Huanwu decoction. Methods Isocratic elution was carried out with mobile phase consisting of methanol- 2 mM ammonium formate. The separation was performed on Agilent ZORBAX SB-C18 maintained at 35 ℃. The flow rate was 200 μl/min, and the injection volume was 2 μl. The mass spectrometer was operated in the positive and negative ionization electrospray (ESI) mode using multiple monitoring (MRM) for analysis of six components. The mass spectrometric conditions were that ion source temperature 400 ℃, dry gas flow 500 L/h, atomization gas flow rate 75.8 Kpa, spray voltage 4 000 V, dry gas temperature 400 ℃. Results The amygdalin, paeoniflorin, ferulic acid, calycosin glucosidase, quercetin and formononetin were all analyzed exactly, and the linear ranges were 0.5-32, 0.2-12.8, 0.1-6.4, 0.8-51.2, 0.4-25.6, 0.08-5.12 ng, respectively. The r were 0.992 1, 0.994 5, 0.992 8, 0.995 8, 0.994 7, 0.996 6, respectively. The recoveries of six analytes ranged from 99.21% to 101.44% and the relative standard deviations were all below 2.05%. Conclusions A sensitive, accuracy and suitable UHPLC-MS/MS method has been developed, and the method could be applied for the determination of amygdalin, paeoniflorin, ferulic acid, calycosin glucosidase, quercetin and formononetin in Buyang-Huanwu decoction. Key words: Bu Yang Huan Wu Tang; UHPLC-MS/MS; Amygdalin; Paeoniflorin; Ferulic acid; Calycosin glucosidase; Quercetin; Formononetin; Quality control

Process Optimization and Upscaling of Spray-Dried Drug-Amino acid Co-Amorphous Formulations.

The feasibility of upscaling the formulation of co-amorphous indomethacin-lysine from lab-scale to pilot-scale spray drying was investigated. A 22 full factorial design of experiments (DoE) was employed at lab scale. The atomization gas flow rate (Fatom, from 0.5 to 1.4 kg/h) and outlet temperature (Tout, from 55 to 75 °C) were chosen as the critical process parameters. The obtained amorphization, glass transition temperature, bulk density, yield, and particle size distribution were chosen as the critical quality attributes. In general, the model showed low Fatom and high Tout to be beneficial for the desired product characteristics (a co-amorphous formulation with a low bulk density, high yield, and small particle size). In addition, only a low Fatom and high Tout led to the desired complete co-amorphization, while a minor residual crystallinity was observed with the other combinations of Fatom and Tout. Finally, upscaling to a pilot scale spray dryer was carried out based on the DoE results; however, the drying gas flow rate and the feed flow rate were adjusted to account for the different drying chamber geometries. An increased likelihood to achieve complete amorphization, because of the extended drying chamber, and hence an increased residence time of the droplets in the drying gas, was found in the pilot scale, confirming the feasibility of upscaling spray drying as a production technique for co-amorphous systems.

Using two-fluid nozzle for spray freeze drying to produce porous powder formulation of naked siRNA for inhalation

Spray freeze drying is an attractive technology to produce powder formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.

Processing Parameter Effects and Thermal Properties of Y2Si2O7 Nanostructured Environmental Barrier Coatings Synthesized by Solution Precursor Induction Plasma Spraying

The solution precursor plasma spray process, in which a solution of metal salts is axially injected into an induction thermal plasma, is suitable for deposition of nanostructured environmental barrier coatings. The effects of main processing parameters, namely the solution precursor concentration, spraying distance, reactor pressure, and atomization gas flow rate, have been analyzed using D-optimal design of experiments regarding the deposition rate and coating porosity responses. Among these four parameters, the solution precursor concentration had the greatest influent on the coating structure, followed by the spraying distance and reactor pressure, and finally the atomization gas flow rate with a small contribution. It is pointed out that the species that impact on the substrate are agglomerates of nanoparticles. The equivalent thermal conductivity of selected coatings was computed from experimental temperature evolution curves obtained by laser flash thermal diffusivity analysis, using two methods: a multilayer finite-element model with optimization, and a multilayer thermal diffusion model. The results of the two models agree, with coatings exhibiting low thermal conductivity between 0.7 and 1 W/(m K) at 800 °C.

Production of fine lactose particles from organic solvent in laboratory and commercial-scale spray dryers

ABSTRACT A laboratory spray dryer and a commercial dryer with a production rate 50 times greater, both using two-fluid nozzles, were used to dry the same formulation from organic solvent. Both dryers generated particles of similar size, with tight particle size distributions (span <2), which varied with atomization gas flow rate, liquid flow rate, and solids concentration. Small-scale results with an external mixing nozzle were fitted to a correlation based on literature recommendations. This also fitted well for the commercial dryer with external mixing, and an internal mixing nozzle gave a tighter size distribution. Hence, successful verification at scale has been achieved.

In-site characterization of bed fluidity in a large gas–solid fluidized bed via electric conductance method

In various industrial applications in which a liquid is sprayed into a gas-fluidized bed such as Fluid CokersTM, fluid catalytic crackers and gas-phase polymerization reactors, parts of the bed or even the complete bed might become defluidized due to high liquid loading, agglomeration or sintering of particles. For instance, in Fluid Cokers, operating at lower temperatures increases the yield of liquid products and reduces sulphur emissions, but local defluidization may result in some bed regions with a disastrous impact on reactor operation. This loss of bed fluidity is called “bogging”.This study examines a novel method employing electrical conductance to detect local bogging in a large scale pilot fluid bed of about 7tonnes of silica sand. Bogging is induced by increasing the liquid load as well as by changing the atomization performance of a spray nozzle. Several other experimental methods, such as differential and static pressure measurements, image processing, and temperature measurements are evaluated.When liquid is injected into a fluidized bed, a fraction forms liquid–solid agglomerates while the remainder forms free moisture, consisting of individual particles coated with a thin layer of liquid. Liquid present as free moisture can be beneficial as it increases the mass and heat transfer processes and increases yields of valuable products. The results indicated that conductance measurements could be used for detecting bogging phenomena online. Bogging is shown to be directly associated with the local free moisture rather than the total moisture level. Increasing the atomization gas flowrate and, consequently, the free moisture, increases the bogging risk. A measurable critical, local free moisture value above which localized bogging occurs is identified.

The effects of liquid properties and bed hydrodynamics on the distribution of liquid on solid fluidized particles in a cold-model fluidized bed

Uniform distribution of liquid feed on fluidized particles increases the yield of valuable products and improves operability in processes such as Fluid Coking™ and Fluid Catalytic Cracking. Contact between the injected liquid and the bed particles can be greatly affected by the liquid properties and local bed hydrodynamics. In this study, the effect of viscosity, contact angle, surface tension, fluidization velocity and atomization gas flowrate on the distribution of liquid sprayed into a fluidized bed was investigated with a reliable and fast response capacitance meter. This method was also extended to monitor the agglomerate breakup kinetics.

Experimental Study of Spray Drying and Atomization with a Two-Fluid Nozzle to Produce Inhalable Particles

A series of 50 experiments was performed to investigate particle size and yield from three laboratory spray dryers with two-fluid nozzles, using an aqueous solution of egg albumin as the feed. First principles theory suggests that the main parameters affecting final particle size should be atomization gas flowrate and velocity, feed solution flowrate, solution concentration, and inlet and outlet gas temperature. The experiments demonstrated that atomization gas velocity at the nozzle correlated better than volumetric gas flowrate to the final particle size obtained. Increasing atomization gas flow gave a decrease in particle size, levelling off at high nozzle gas velocities approaching sonic values. Liquid flowrate had little effect, and hybrid ratios such as the ALM (atomization gas to liquid flow ratio) did not correlate well to measured final particle size for this system. This seems likely to apply to aqueous systems with temperature limitations, where liquid flowrates will be relatively low compared to gas flowrates (both atomization and main gas flow). Particle size generally increased with solution concentration, and in some cases scaled exactly, assuming a constant initial droplet size and final particle density. All experiments were performed below the boiling point and therefore temperature had little effect. Particles of 2–3 microns were obtained at high atomization gas flows, indicating initial droplet sizes of 4–7 microns at most, while lower flowrates gave substantially larger particles and a wider size distribution.

Spray drying for preservation of erythrocytes: effect of atomization on hemolysis.

Spray drying has the potential to enable storage of erythrocytes at room temperature in the dry state. The spray drying process involves atomization of a liquid into small droplets and drying of the droplets in a gas stream. In this short report, we focus on the atomization process. To decouple atomization from drying, erythrocyte suspensions were sprayed with a two-fluid atomizer nozzle using humid nitrogen as the atomizing gas. The median droplet size was less than 100 μm for all of the spray conditions investigated, indicating that the suspensions were successfully atomized. Hemolysis was significantly affected by the hematocrit of the erythrocyte suspension, the suspension flow rate, and the atomizing gas flow rate (p<0.01 in all cases). Under appropriate conditions, it was possible to achieve less than 2% hemolysis, suggesting that spray drying may be a feasible option for erythrocyte biopreservation.

Advancement of In-Flight Alumina Powder Spheroidization Process with Water Droplet Injection Using a Small Power DC-RF Hybrid Plasma Flow System

The correlation between plasma thermofluid characteristics and alumina powder spheroidization processes with water droplet injection using a small power DC-RF hybrid plasma flow system was experimentally clarified. Micro-sized water droplets with a low water flow rate were injected into the tail of thermal plasma flow so as not to disturb the plasma flow directly. Injected water droplets were vaporized in the thermal plasma flow and were transported upstream in the plasma flow to the torch by the backflow. After dissociation of water, the production of hydrogen was detected by the optical emission spectroscopy in the downstream RF plasma flow. The emission area of the DC plasma jet expanded and elongated in the vicinity of the RF coils. Additionally, the emission area of RF plasma flow enlarged and was visible as red emission in the downstream RF plasma flow in the vicinity below the RF coils due to hydrogen production. Therefore, the plasma flow mixed with produced hydrogen increased the plasma enthalpy and the highest spheroidization rate of 97% was obtained at a water flow rate of 15 Sml/min and an atomizing gas flow rate of 8 Sl/min using a small power DC-RF hybrid plasma flow system.

Experimental modeling of polymer latex spray coating for producing controlled-release urea

Spray coating of polymer latex onto fertilizer particles in a fluidized bed for producing controlled-release urea is an environment friendly technology as it does not need any toxic organic solvent. Since the spray coating process in a fluidized bed occurs in the presence of particle collisions, the coating of the particles is random, intermittent and multiple, thus making it difficult to investigate the film formation process. In this paper, an experimental model apparatus was designed and used to investigate the effects of the key factors in the spray coating process. This apparatus reasonably simplified the complex process to avoid particle collisions and randomness in the coating. The intermittent coating in the fluidized bed was modeled by periodic coating and dewatering in the experimental apparatus. A large area film was obtained, and the film permeability was measured. The effects of atomizing gas flow rate, spray rate of latex, solid content of latex and gas temperature on film structure and film permeability were investigated. It was found that water transfer played a dominant role in the spray coating process.

Comparison of the performance of liquid–gas injection nozzles in a gas–solid fluidized bed

It is often necessary to inject a liquid in fluidized bed reactors, such as fluid cokers, fluid catalytic crackers and gas-phase polymerization reactors. A more uniform dispersion of the injected liquid over the bed solids minimizes agglomeration, and prevents mass and heat transfer limitations, resulting in improved reactor operability and increased yields of desired products. The quality of the injection can be significantly affected by nozzle design and by several operating parameters. The goal of the current study was to compare several gas-assisted liquid injection nozzles under a variety of operating conditions. The nozzles sprayed water atomized with air into a bed of silica sand particles fluidized with air. The quality of the jet-bed interaction associated with each experiment was characterized using a conductive probe method, which uses the measured electrical conductance of the bed. It has been found that the bed conductance increases as the liquid becomes more uniformly dispersed throughout the fluidized bed. The droplet size of the injected spray was also measured in open air using a laser scattering system. In all tests, the liquid flowrate was held constant, while the atomization gas flowrate was varied. It was found that different nozzles displayed their best performance at different gas flowrates. Large droplets tended to negatively impact the spread of liquid throughout the bed, especially when they were larger than the fluidized particles. Large fluctuations in the water flowrate tended to decrease the performance of the nozzles. Multi-linear regression was used to correlate the nozzle performance to various nozzle parameters.

Droplet Size Measurements for Spray Dryer Scale-Up

This study was dedicated to facilitate scale-up in spray drying from an atomization standpoint. The purpose was to investigate differences in operating conditions between a pilot and a production scale nozzle. The intension was to identify the operating ranges in which the two nozzles produced similar droplet size distributions. Furthermore, method optimization and validation were also covered. Externally mixing two-fluid nozzles of similar designs were used in this study. Both nozzles are typically used in commercially available spray dryers, and they have been characterized with respect to droplet size distributions as a function of liquid type, liquid flow rate, atomization gas flow rate, liquid orifice diameter, and atomization gas orifice diameter. All droplet size measurements were carried out by using the Malvern Spraytec with nozzle operating conditions corresponding to typical settings for spray drying. This gave droplets with Sauter Mean Diameters less than 40 μm and typically 5–20 μm. A model previously proposed by Mansour and Chigier was used to correlate the droplet size to the operating parameters. It was possible to make a correlation for water incorporating the droplet sizes for both the pilot scale and the production scale nozzle. However, a single correlation was not able to account properly for the physical properties of the liquid to be atomized. Therefore, the droplet size distributions of ethanol could not be adequately predicted on the basis of the water data. This study has shown that it was possible to scale up from a pilot to production scale nozzle in a systematic fashion. However, a prerequisite was that the nozzles were geometrically similar. When externally mixing two-fluid nozzles are used as atomizers, the results obtained from this study could be a useful guideline for selecting appropriate operating conditions when scaling up the spray-drying process.

Characterization of SiC and Si3N4 coatings synthesized by means of inductive thermal plasma from disilane precursors

AbstractThe synthesis of SiC (and/or Si3N4) in an inductive thermal plasma from liquid disilane precursor is described in this paper. One goal of the process presented hereafter is the valorization of a liquid disilane fraction, which is a by‐product of the silicone industry. The liquid precursor is atomized in the core of the thermal inductive plasma and decomposed in the high‐temperature zone. The coating grows on the substrate according to the thermal plasma chemical vapor deposition (CVD) process. The resulting synthesized materials are investigated by means of X‐ray diffraction, scanning and transmission electron microscopy, and nuclear magnetic resonance. The composition of the material synthesized is studied as a function of process parameters, such as the plasma gas nature and its composition, the atomization gas flow rate and the plasma reactor pressure. Control over the composition of the synthesized material composition, as well as the coating microstructure, can be achieved by an appropriate adjustment of the experimental parameters. Nanostructured α/β‐SiC and α/β‐Si3N4 can be synthesized successfully with such a thermal plasma process. The deposition rate reached with such a technology is more than 20 μm min−1, which is two to three orders of magnitude higher than that of the conventional CVD method. Copyright © 2001 John Wiley &amp; Sons, Ltd.