On the Fabrication of Microparticles Using Electrohydrodynamic Atomization Method

A new approach for the control of the size of particles fabricated using the Electrohydrodynamic Atomization (EHDA) method is being developed. In short, the EHDA process produces solution droplets in a controlled manner, and as the solvent evaporates from the surface of the droplets, polymeric particles are formed. By varying the voltage applied, the size of the droplets can be changed, and consequently, the size of the particles can also be controlled. By using both a nozzle electrode and a ring electrode placed axisymmetrically and slightly above the nozzle electrode, we are able to produce a Single Taylor Cone Single Jet for a wide range of voltages, contrary to just using a single nozzle electrode where the range of permissible voltage for the creation of the Single Taylor Cone Single Jet is usually very small. Phase Doppler Particle Analyzer (PDPA) test results have shown that the droplet size increases with increasing voltage applied. This trend is predicted by the electrohydrodynamic theory of the Single Taylor Cone Single Jet based on a perfect dielectric fluid model. Particles fabricated using different voltages do not show much change in the particles size, and this may be attributed to the solvent evaporation process. Nevertheless, these preliminary results do show that this method has the potential of providing us with a way of fine controlling the particles size using relatively simple method with trends predictable by existing theories.

Electrohydrodynamic Atomization for Improved Macromolecular Drug Delivery

With advances in drug research, the use of biological therapeutics is becoming a reality. Unfortunately, methods for processing and delivering these fragile macromolecules often limit their therapeutic potential. For this dissertation, we explore the aerosolization of macromolecules by way of electrohydrodynamic atomization (EHDA) and how this method can be used to process and deliver therapeutics. EHDA employs a high voltage to break a column of liquid into drops. It was unknown if or how the residual charge left of the resulting droplets would affect lung cells. An in vitro experiment was conducted to spray aerosolized DNA, by way of EHDA, onto human derived lungs cells to test for immunogenic and toxic effects. The lung cells displayed no immunogenic or toxic response to the DNA or high voltage. Previous researchers have used EHDA to aerosolize proteins with mixed results. This work sets forth a simplified thermodynamic theory and provides recommendations to pharmaceutical companies on how to design more stable protein formulations for aerosol processing or delivery. Finally, a new method of producing liposomes was created. It constructs the liposome one layer at a time. The inside of the liposome is sprayed by EHDA, with the lipid and drug in solution together. As the sprayed monolayer passes through a pool containing a solution of lipid in water, the second part of the bilayer attaches to the inner layer creating a complete bilayer liposome.

Periodic emission of droplets from an oscillating electrified meniscus of a low-viscosity, highly conductive liquid

The generation of identical droplets of controllable size in the micrometer range is a problem of much interest owing to the numerous technological applications of such droplets. This work reports an investigation of the regime of periodic emission of droplets from an electrified oscillating meniscus of a liquid of low viscosity and high electrical conductivity attached to the end of a capillary tube, which may be used to produce droplets more than ten times smaller than the diameter of the tube. To attain this periodic microdripping regime, termed axial spray mode II by Juraschek and Röllgen [R. Juraschek and F. W. Röllgen, Int. J. Mass Spectrom. 177, 1 (1998)], liquid is continuously supplied through the tube at a given constant flow rate, while a dc voltage is applied between the tube and a nearby counter electrode. The resulting electric field induces a stress at the surface of the liquid that stretches the meniscus until, in certain ranges of voltage and flow rate, it develops a ligament that eventually detaches, forming a single droplet, in a process that repeats itself periodically. While it is being stretched, the ligament develops a conical tip that emits ultrafine droplets, but the total mass emitted is practically contained in the main droplet. In the parametrical domain studied, we find that the process depends on two main dimensionless parameters, the flow rate nondimensionalized with the diameter of the tube and the capillary time, q, and the electric Bond number BE, which is a nondimensional measure of the square of the applied voltage. The meniscus oscillation frequency made nondimensional with the capillary time, f, is of order unity for very small flow rates and tends to decrease as the inverse of the square root of q for larger values of this parameter. The product of the meniscus mean volume times the oscillation frequency is nearly constant. The characteristic length and width of the liquid ligament immediately before its detachment approximately scale as powers of the flow rate and depend only weakly on the applied voltage. The diameter of the main droplets nondimensionalized with the diameter of the tube satisfies dd≈(6/π)1/3(q/f)1/3, from mass conservation, while the electric charge of these droplets is about 1/4 of the Rayleigh charge. At the minimum flow rate compatible with the periodic regimen, the dimensionless diameter of the droplets is smaller than one-tenth, which presents a way to use electrohydrodynamic atomization to generate droplets of highly conducting liquids in the micron-size range, in marked contrast with the cone-jet electrospray whose typical droplet size is in the nanometric regime for these liquids. In contrast with other microdripping regimes where the mass is emitted upon the periodic formation of a narrow capillary jet, the present regime gives one single droplet per oscillation, except for the almost massless fine aerosol emitted in the form of an electrospray.

Process considerations related to the microencapsulation of plasmid DNA via ultrasonic atomization

An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

Creation of protein loaded biodegradable microparticles via ultrasonic atomization suitable for nasal delivery

Improved biopharmaceutical delivery may be achieved via the use of biodegradable microspheres as delivery vehicles. Biodegradable microspheres offer the advantages of maintaining sustained protein release over time whilst simultaneously protecting the biopharmaceutical from degradation. Particle samples produced by ultrasonic atomization were studied in order to determine a feed stock capable of producing protein loaded poly-ε-caprolactone (PCL) particles suitable for nasal delivery (i.e., less than 20 μm). A 40 kHz atomization system was used with a 6 mm full wave atomization probe. The effect of solids percent, feed flow rate, volumetric ratio of the polymer stock to the protein stock, and protein concentration in the protein stock on particle size characteristics were determined. It was shown that feed stocks containing 100 parts of 0.5 or 1.0% w/v PCL in acetone with one part 100 mg ml -1 BSA and 15 mg ml -1 PVA produced particles with a mass moment diameter (D[4,3]) of 13.17 μm and 9.10 μm, respectively in addition to displaying high protein encapsulation efficiencies of 93 and 95%, respectively. The biodegradable PCL particles were shown to be able to deliver encapsulated protein in vitro under physiological conditions.

Straightforward biodegradable nanoparticle generation through megahertz-order ultrasonic atomization

Simple and reliable formation of biodegradable nanoparticles formed from poly-ε-caprolactone was achieved using 1.645 MHz piston atomization of a source fluid of 0.5% w/v of the polymer dissolved in acetone; the particles were allowed to descend under gravity in air 8 cm into a 1 mM solution of sodium dodecyl sulfate. After centrifugation to remove surface agglomerations, a symmetric monodisperse distribution of particles φ 186 nm (SD=5.7, n=6) was obtained with a yield of 65.2%. © 2006 American Institute of Physics.

Production of biodegradable nano and micro particles via ultrasonic atomization for biopharmaceutical delivery

Biopharmaceuticals have been shown to have low delivery and transformation efficiencies. To over come this, larger doses are administered in order to obtain the desired response which may lead to toxicity and drug resistance. This paper reports upon a continuous particle production method utilizing surface acoustic wave atomization to reliably produce micro and nanoparticles with physical characteristics to facilitate the cellular uptake of biopharmaceuticals. By producing particles of an optimal size for cellular uptake, the efficacy and specificity of drug loaded nanoparticles will be increased. Better delivery methods will result in dosage reduction (hence lower costs per dose), reduced toxicity, and reduced problems associated with multidrug resistance due to over dosing.

Studies on pneumatic atomization

A study of atomization has been made with an external mixing-type pneumatic atomizer. The drops were sampled on Vaseline-coated cells using a shutter arrangement and their sizes were measured under a microscope. The effects of liquid viscosity, liquid surface tension, liquid flow rate, air velocity, and nozzle angle on drop size have been studied. A model, which explains adequately the influence of various factors, has been proposed. This model predicts the values of average drop sizes over a wide range of operating conditions. The model also explains the data of other investigators who have used other kinds of pneumatic atomizers.

Thermally induced secondary atomization of droplet in an acoustic field

We study the thermal effects that lead to instability and break up in acoustically levitated vaporizing fuel droplets. For selective liquids, atomization occurs at the droplet equator under external heating. Short wavelength [Kelvin-Helmholtz (KH)] instability for diesel and bio-diesel droplets triggers this secondary atomization. Vapor pressure, latent heat, and specific heat govern the vaporization rate and temperature history, which affect the surface tension gradient and gas phase density, ultimately dictating the onset of KH instability. We develop a criterion based on Weber number to define a condition for the inception of secondary atomization. (C) 2012 American Institute of Physics. [doi:10.1063/1.3680257]

Spreading and atomization of droplets on a vibrating surface in a standing pressure field

We report the first observation and analytical model of deformation and spreading of droplets on a vibrating surface under the influence of an ultrasonic standing pressure field. The standing wave allows the droplet to spread, and the spreading rate varies inversely with viscosity. In low viscosity droplets, the synergistic effect of radial acoustic force and the transducer surface acceleration also leads to capillary waves. These unstable capillary modes grow to cause ultimate disintegration into daughter droplets. We find that using nanosuspensions, spreading and disintegration can be prevented by suppressing the development of capillary modes and subsequent break-up. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4757567]

AN EXPERIMENTAL STUDY ON EFFERVESCENT ATOMIZATION OF BIO-OIL FUELS

This paper presents the work on detailed characterization of effervescent spray of Jatropha and Pongamia pure plant oils. The spray characteristics of these biofuels are compared with those of diesel. Both macroscopic and microscopic spray characteristics at different injection pressures and gas-to-liquid ratio (GLR) have been studied. The particle/droplet imaging analysis (PDIA) technique along with direct imaging methods are used for the purpose of spray characterization. Due to their higher viscosity, pure plant oils showed poor atomization compared to diesel and a blend of diesel and pure plant oil at a given GLR. Pure plant oil sprays showed a lower spray cone angle when compared to diesel and blends at lower GLRs. However, the difference is not significant at higher GLRs. Droplet size measurements at 100 mm downstream of the exit orifice showed reduction in Sauter mean diameter (SMD) diameter with increase in GLR. A radial variation in the SMD is observed for the blend and pure plant oils. Pure oils showed a larger variation when compared to the blend. Spray unsteadiness has been characterized based on the image-to-image variation in the mean droplet diameter and fluctuations in the spray cone angle. Results showed that pure plant oil sprays are more unsteady at lower GLRs when compared to diesel and blend. A critical GLR is identified at which the spray becomes steady. The three regimes of spray operation, namely ``steady spray,'' ``pulsating spray,'' and ``spray and unbroken liquid jet'' are identified in the injection pressure-GLR parameter space for these pure plant oils. Two-phase flow imaging inside the exit orifice shows that for the pure plant oils, the flow is highly transient at low GLRs and the bubbly, slug, and annular two-phase flow regimes are all observed. However, at higher GLRs where the spray is steady, only the annular flow regime is observed.

Criteria for thermally induced atomization and catastrophic breakup of acoustically levitated droplet

We report thermally induced instability leading to catastrophic breakup in acoustically levitated vaporizing fuel droplets. Change in surface tension and viscosity with increase in droplet temperature causes wide fluctuations in droplet aspect ratio. If the viscous damping of aspect ratio oscillation is not strong enough, the droplet goes through unbounded stretching. If the droplet exceeds a critical Weber number locally, a bag type and capillary wave induced atomization can occur, which leads to catastrophic breakup. A stability criterion has been established based on the inhomogeneity of Bernoulli (acoustic) pressure and surface tension of the droplet in terms of a local Weber number and Ohnesorge number. This instability is thermally induced in a droplet which does not experience instabilities without heating. (C) 2012 Elsevier Ltd. All rights reserved.