Droplet-Phase Synthesis of Nanoparticle Aerosol Lipid Matrices with Controlled Properties

Nanoparticle lipid matrices are being recently explored for controlled drug delivery applications. The degree of crystallinity of the lipid matrix governs drug loading capacity and release rates. Current methods of preparing nanoparticle lipid matrices, like high-pressure homogenization and solvent-emulsification evaporation, offer limited or poor control over lipid crystallinity. The present work explores a droplet-phase aerosol synthesis method to prepare nanoparticle aerosol lipid matrices (NALM). Control of evaporation rate was used to achieve control over crystallinity of NALM. NALM were synthesized in an aerosol reactor using precursor solutions of stearic acid in organic solvents with widely different vapour pressures, resulting in different rates of evaporation. Mean mobility diameter, measured using a scanning mobility particle sizer (SMPS), ranged from 94–127 nm, with a unimodal distribution and geometric standard deviation of 1.7–1.9. Aerodynamic diameters measured using gravimetric analysis of samples collected in a micro-orifice cascade impactor, ranged from 423–608 nm. Relatively higher peak intensities and peak areas in X-ray diffractograms, and higher melting enthalpies in the differential scanning calorimetry (DSC) thermograms were obtained for NALM synthesized under lower evaporation rates, using lower vapour pressure solvents, similar to that of bulk stearic acid. In contrast, NALM synthesized at higher evaporation rates, using higher vapour pressure solvents consistently showed a lower degree of crystallinity, evidenced by blunt X-ray diffraction peaks and lower melting enthalpies in DSC analysis. These results suggest the formation of non-equilibrium crystal structures within NALM, under the influence of faster evaporation rates, leading to a lower degree of crystallinity. The work demonstrates proof of concept of droplet-phase aerosol synthesis for preparing nanoparticle lipid matrices and for achieving control over their crystallinity.     

Investigation of a Novel Condensation Aerosol Generator: Solute and Solvent Effects

Part I of this article presents results of an experimental study on gas-phase nucleation for three model solutes and their solvent, propylene glycol (PG), with variables being solute concentration and the nature of the solute substance. A single manifestation of an aerosol generator, which forms condensation aerosols by cooling of hot vapor issuing from an electrically heated, pumped capillary, is described and used for all experiments. The effects of solute concentration and solute type were studied for deoxycorticosterone (DOC), benzil (BZ), and phenyl salicylate (PhS). Suppression of homogeneous nucleation and occurrence of heterogeneous condensation of the solvent was observed at different solute concentrations for BZ, PhS, and DOC. The nature and concentration of the solute dissolved in the solvent was shown to determine the final particle size distribution of the condensed aerosol. In the case of the least volatile solute, DOC, solute aerosol and total aerosol size distributions were identical at low solute concentrations. A transitional concentration region then existed in which a bimodal solute aerosol was formed, followed at high concentrations by increasing separation of the solvent-dominated aerosol size distribution and that of the solute. In Part II of this article, the effect of DOC dissolution in different solvents was studied at fixed solute concentration. The effects of six glycol solvents--i.e., PG, ethylene glycol (EG), dipropylene glycol (DPG), diethylene glycol (DEG), triethylene glycol (TEG), and tetraethylene glycol (TetEG)--and three nonglycol solvents--i.e., dimethyl sulfoxide (DMSO), formamide (FORM), and oleyl alcohol (OA)--were studied, as these affected the resultant aerosol sizes. Suppression of total aerosol mass median aerodynamic diameter (MMAD) was observed on dissolution of 0.5% w/w DOC in each solvent, although suppression occurred to different extents. It was shown that the boiling point or volatility of the solvent used to dissolve the less volatile DOC had an effect on the final particle size distribution of the condensed aerosol and whether the aerodynamic size distributions for the solute and the total aerosol were the same or different.     

Modeling and design of an industrial dryer with convective and radiant heating

Industrial equipment for drying polymeric coatings normally consists of a series of zones, each with a controlled temperature and airflow. Drying of a polymer–solvent solution is strongly affected by the variation of diffusivity, solvent vapor pressure, and solvent activity with temperature and composition. The equations of mass transfer by diffusion and of heat transfer by conduction and radiation describe changes in composition and temperature within the shrinking coating. This system of equations is solved by Galerkin's method with finite element basis functions. The boundary conditions on dryer airflow and temperature change at the entrance to each zone. In a few test cases, the predictions show how evaporative cooling can slow drying in early zones where the coating temperature drops below the dryer temperature, whereas in later zones the coating temperature rapidly approaches the dryer temperature. Infrared heating can be used to reduce the extent of evaporative cooling. In the test cases and experiments, “blistering” occurs in later zones where high oven temperature causes the solvent partial pressure to rise; dryer parameters can be chosen to maintain solvent partial pressure just below ambient pressure in order to avoid “blistering” with least sacrifice of process speed. © 1995 John Wiley & Sons, Inc.     

Transient rise velocity and mass transfer of a single drop with interfacial instabilities - experimental investigations

An experimental study of transient drop rise velocities and mass transfer rates was carried out in the system toluene/acetone/water which is known to show interfacial instabilities. The rise velocity of toluene drops was studied without added solute (acetone) in the diameter range 1-3 mm and with added solute for 2 mm drops. The initial concentration of the transferred solute was varied from 0 to 30 g/L. The transient drop rise velocities were used to quantify the Marangoni effect since the drag coefficient depends on the strength of the Marangoni convection patterns caused by interfacial tension gradients. In addition, mass transfer measurements were carried out in order to determine the modification of the mass transfer rate due to Marangoni convection. Velocity and mass transfer measurements were then correlated via the contact time. Results reveal the existence of a range in which a critical value for the solute concentration can be defined for Marangoni convection.     

HD低温蒸发系统中填料蒸发器传质传热的分析

通过研究系统中填料蒸发器的蒸发传质传热过程以及两相流动特性，采用计算流体力学（computational fluid dynamics，CFD）中离散相与连续相耦合的方法来模拟规整填料内部通道的蒸发传质传热过程，实现了填料蒸发器中两相传质传热的过程以及液滴流动的可视化，为研究气液两相在规整填料内的流动提供了一种模拟方法。通过与实验结果的比较，最终选用RNG k-ε湍流模型来分析规整填料内部气液两相传质传热以及流动情况。数值模拟研究了规整填料板间距对填料内部气液两相传质传热以及液滴运动影响，发现随着板间距的增大，填料内部压力降逐渐降低，出口空气中水蒸气的含量不断减小，液滴蒸发速率降低，液滴进出口质量差减小，气相出口温度逐渐降低，蒸发传质传热效率降低。随着气速的增大，出口空气中水蒸气的含量不断减小，液滴蒸发速率增加，气相出口温度降低，气液两相传质传热效率降低。     

Span 60 as a Microsphere Matrix: Preparation and in Vitro Characterization of Novel Ibuprofen-Span 60 Microspheres

Microspheres are a potential delivery system for controlled and sustained drug release. Polymeric microspheres are commonly prepared by the solvent evaporation technique whereas waxy microspheres by the melt dispersion technique. The goal of this study was to prepare a surfactant (Span 60)—Ibuprofen microspheres using both techniques. Ibuprofen‐Span 60 microspheres were fabricated with different drug to polymer weight ratios of 3:1, 1:1 and 1:3 and characterized by particle size, in vitro dissolution, infrared spectroscopy, x‐ray diffraction and scanning electron microscopy. The actual drug content increased with increasing the concentration of anti‐aggregating agent (polyvinylpyrolidone). The actual drug content and drug encapsulation efficiency was markedly higher in case of microspheres prepared by a solvent evaporation technique compared to that prepared by a melt dispersion one using the same theoretical drug content. The microspheres were spherical with irregular surfaces. The in vitro release showed no burst effect and incomplete drug release. The rate and total drug released from the microspheres prepared by a solvent evaporation technique are higher than those prepared by using the melt dispersion technique. FTIR rolled out the chemical changes of the drug in Span 60 microspheres. The X‐ray diffraction pattern of the microspheres prepared by using a solvent evaporation technique showed a decrease in the drug crystallinity. The drug crystallinity in microspheres prepared by the melt dispersion technique decreased with increasing the theoretical drug content. The drug entrapment mechanism is responsible for the changes in drug physicochemical properties and in vitro release.     

Evaporative cooling of micron-sized droplets in a low-pressure aerosol reactor

The results of experimental and computational investigation of evaporative cooling of micron-sized droplets in a low-pressure aerosol reactor (LPAR) are reported. The cooling rate of the aerosol was found to be about . A constant low pressure, the flow rates of the carrier gas and solution are major factors that affect droplet cooling. A higher total pressure accelerated the change in droplet radius. For some regimes it was predicted that an aerosol undergoes freezing and then melting. The characteristic time required for evaporative cooling is about 1 ms. The agreement between experimental results and calculated values, based on the free molecular approximation of heat and mass transfer processes, is reasonably good.     

Particle formation and characteristics of Celecoxib-loaded poly(lactic-co-glycolic acid) microparticles prepared in different solvents using electrospraying

Microparticles were fabricated for pharmaceutical purposes using electrospraying with the aim to determine the effect of the solvent(s) used. Particles of poly(lactic-co-glycolic acid) (PLGA) and the drug Celecoxib were prepared from acetone, acetonitrile and acetone:methanol with different polymer and drug concentrations. The solvent power, evaporation rate and electrical conductivity of the solvents all had a significant effect on the particle formation process as well as the particle characteristics and drug release profile. Particles were near-spherical and between 2 and 7 μm in diameter with smooth or corrugated surfaces. The drug release rate was mainly dependent on particle size, with larger particles showing slower release. The solvent in which PLGA was poorly soluble resulted in small grainy particles that disintegrated instantaneously with full drug release. It may be concluded that the selection of an appropriate solvent may be a useful way to control particle characteristics and drug release profiles when using electrospraying.     

Volatile Metal Oxide Evaporation during Aerosol Decomposition

The role of particle evaporation during synthesis of volatile metal oxide powders (Bi₂O₃, MoO₃, PbO, and V₂O₅) by aerosol decomposition (spray pyrolysis) in a heated flow reactor was investigated. Solid particles (0.1–0.6 (Am) of predominantly β-Bi₂O₃ were formed with smooth spherical shape at all reactor temperatures (673–1173 K) employed. Solid MoO₃ particles (0.1–1.2 μm) produced at low temperatures (673–773 K) had a roughly spherical or faceted morphology and at high temperatures (873 K) had a platelike or layered structure. Solid V₂O₅ particles produced at low temperatures (573–673 K) were spherical and at high temperatures (973–1073 K) were platelike. The PbO particles were solid and spherical for all temperatures studied (773°–1073°C). Evaporative losses of up to 100% to the reactor walls were observed for all the metal oxides, due to their substantial vapor pressures. The evaporative losses were modeled by considering simultaneous particle evaporation and mass transfer of the metal oxide vapor to the reactor walls. The calculations indicated that, for most of these volatile metal oxides, evaporative losses were limited by diffusional transport of the vapor to the reactor walls and that evaporative losses occur when the vapor pressure of the oxides in the reactor is above 10^-5-10^-3 mm Hg.     

Determination of the peripheral contact angle of sessile drops on solids from the rate of evaporation

A method was developed to determine the initial peripheral contact angle of sessile drops on solid surfaces from the rate of drop evaporation for the case where ₁ < 90°. The constant drop contact radius, the initial weight, and the weight decrease with time should be measured at the ambient temperature for this purpose. When water drops are considered, the relative humidity should also be known. The peripheral contact angle so obtained is regarded as the average of all the various contact angles existing along the circumference of the drop. Thus, each determination yields an average result not unduly influenced by irregularities at a given point on the surface. In addition, the error in personal judgment involved in drawing the tangent to the curved drop profile at the point of contact can be eliminated. The application of this method requires the use of the product of the vapor diffusion coefficient with the vapor pressure at the drop surface temperature. This product can be found experimentally by following the evaporation of fully spherical liquid drops.     

Direct contact heat transfer between two immiscible liquids during vaporization: Part II: Total evaporation time

A dilatometric technique was used to determine the total evaporation time of individual drops of furan, isopentane and cyclopentane as they rose in water. The values of total evaporation time were predicted reasonably well for each system by a different equation than was used to correlate the evaporative data for the initial 10% of the evaporative process as reported in Part I of this study. The total evaporation time data were also compared with the correlations given by Klipstein ⁽¹⁾, by Sideman and Taitel ⁽²⁾ and with the correlation which was found by the authors to best fit the total evaporative data for the three systems. In agreement with Klipstein ⁽¹⁾, the correlation for the overall heat transfer coefficient was found to be one of the form, q_A = Cd₁^2.0δt. The rate of rise of an evaporating drop for the conditions used in this study was found to be nearly equal to the instantaneous terminal velocity.     

On a Petrov-Galerkin Finite Element Method for Evaporation of Polydisperse Aerosols

A Petrov-Galerkin finite element method is derived for evaporation of polydisperse aerosols. It is demonstrated that this numerical method is accurate and computationally efficient. Together with an appropriate grid system and upwinding factor, this method can reduce spurious oscillations to a negligible level and provide reliable results for a wide range of initial size distributions and evaporation rates. Its performance is superior to the upwind differencing method and the sectional method. It is also shown that analytical solutions are very useful in a priori design of grid systems for simulations of realistic aerosol systems, and evaporative cooling is a significant factor in modeling evaporation of polydisperse volatile aerosols.     

Scale-up of nanoparticle synthesis in diffusion flame reactors

The scaling-up of diffusion flame aerosol reactors is investigated for synthesis of nanoparticles. Three co-flow burners of different dimensions are studied at various precursor, oxidant and fuel flow rates. An operation line relating product particle size with reactant outlet conditions, flow rate and burner size is developed showing how the three reactors can produce silica and titania nanoparticles of the same size and morphology. This operation line shows the limit of fast reactant mixing where the diffusion flame aerosol reactors perform as premixed ones. An operation diagram is obtained for different silica production rates and a scale-up procedure is developed.     

Solvent evaporation and spray drying technique for micro- and nanospheres/particles preparation: A review

This article presents a comprehensive review of research relating to the preparation of biodegradable and biocompatible controlled/sustained release of micro and nanoparticles. It covers recent developments in the area of technology through solvent evaporation followed by lyophilization and spray drying. The last decade seen a shift from empirical formulation efforts to a technological approach based on better understanding of micro and nanoparticle formation in the solvent evaporation and spray drying technique. This review provides concepts and a theoretical framework for the preparation of micro and nanoparticle formation. Encapsulation of pharmaceutical materials has received much attention due to enhanced effectiveness, bioavailability, and the dissolution rates that can be achieved. Polymeric micro and nanoparticles can be used to transport drug in a rate-controlled and sometimes targeted manner. Initially, laboratory-scale experiments are performed, but for industrial scale-up, experiments are required using sophisticated technologies. The objective of this review article is to summarize the solvent evaporation and spray drying techniques for the preparation of biodegradable and biocompatible controlled/sustained release of micro and nanospheres/particles with focus on the steps involved in its preparation, materials used, and the technique of microencapsulation. The review also summarizes recent research on solvent evaporation and spray drying.     

Design of gas‐phase synthesis of core‐shell particles by computational fluid–aerosol dynamics

Core‐shell particles preserve the bulk properties (e.g., magnetic and optical) of the core while its surface is modified by a shell material. Continuous aerosol coating of core TiO₂ nanoparticles with nanothin silicon dioxide shells by jet injection of hexamethyldisiloxane precursor vapor downstream of titania particle formation is elucidated by combining computational fluid and aerosol dynamics. The effect of inlet coating vapor concentration and mixing intensity on product shell thickness distribution is presented. Rapid mixing of the core aerosol with the shell precursor vapor facilitates efficient synthesis of hermetically coated core‐shell nanoparticles. The predicted extent of hermetic coating shells is compared with the measured photocatalytic oxidation of isopropanol by such particles as hermetic SiO₂ shells prevent the photocatalytic activity of titania. Finally, the performance of a simpler, plug‐flow coating model is assessed by comparisons with the present detailed computational fluid dynamics (CFD) model in terms of coating efficiency and silica average shell thickness and texture. © 2011 American Institute of Chemical Engineers AIChE J, 2011     

Detection of RDX traces at the surface with sonic aerosol flow desorption

The use of a high-speed aerosol flow is proposed for sampling RDX from the surface followed by chromatographic analysis. The aerosol is generated from different solvents by means of a coaxial nebulizer. The effect of the aerosol flow parameters (solvent flowrate, an angle of the nebulizer inclination with respect to the surface) and various solvents (water, acetone, and hexane) on the efficiency of the RDX desorption was investigated. The optimal angle of the nebulizer was found to be 30°, under these conditions, the desorption of RDX from the surfaces of different structure (metal, glass, leather, cotton fabric, and paper) has also been studied. It is shown that under the action of an aerosol created using water and acetone, desorption from a smooth surface occurs most efficiently (1.5 times higher than with hexane). In this case, the sample removes almost completely (about 80%) by the aerosol flow in a few seconds. A relationship between the desorption efficiency and the amount of the solvent sprayed (that is the amount of aerosol particles in desorbing flow) has a characteristic maximum which location depends on the properties of the solvent spray. This effect is associated with a rate of solvent evaporation. Under optimal conditions for desorption of RDX from a smooth surface using an aqueous aerosol, an LOD of ～10?ng can be achieved. For porous and rough surfaces, the efficiency of the analyte desorption decreases (three times for leather and cotton fabric). The results of the experiments conducted allow one to conclude that the RDX solubility in the solvent used does not affect considerably the efficiency of the RDX desorption. It is assumed that small aerosol drops are very active and can capture the particles of the target analyte. This promotes the desorption of RDX molecules from the surface.

© 2018 American Association for Aerosol Research     

基于不同类型溶液蒸气压特性的太阳能界面蒸发实验研究

太阳能界面蒸发可实现高效太阳能海水淡化和蒸发式污水处理,但目前的研究大多局限于纯水或NaCl溶液。实际脱盐或废水处理中溶质会与此不同,导致溶液蒸气压变化并影响蒸发性能。本文首先分析了溶液表面蒸气压曲线类型,将其分为上凸型、下凹型和直线型。针对这几种蒸气压曲线进一步选取[EMIM][OTf]、[EMIM][Ac]和NaCl水溶液作为代表溶液,在不同辐照强度和浓度下进行了实验研究,并与纯水的蒸发作对比。实验结果表明：低浓度下[EMIM][OTf]水溶液展现出了良好的蒸发性能, 主要原因是由于其蒸气压处于上凸区间;当溶液浓度升高或辐照强度提升时,[EMIM][OTf]溶液的蒸发速率提升较NaCl水溶液小,主要原因在于蒸发过程的浓度极化导致气液界面处的[EMIM][OTf]浓度升高,蒸气压相差较小;不同工况下[EMIM][Ac]水溶液的蒸发速率均较慢,纯水的蒸发速率最快,体现了蒸气压对蒸发性能的关键影响,原因是低蒸气压导致高蒸发温度,并带来更多的能量损失。     

Evaporative analyser as a mass detector in the size-exclusion chromatography of coal extracts

The applicability of the evaporative analyser in the size-exclusion chromatography (SEC) of coal derivatives has been explored. The detector, in which the intensity is measured for the light scattered from the finely divided solute particles resulting from evaporation of droplets of chromatographic eluate, is mass responsive, sensitive, and linear for both narrow and gross coal-extract fractions. For molecular masses above 300 the mass response is almost uniform, and there are considerable advantages over the detectors commonly used in SEC. Application to lower molecular mass coal materials is limited by the evaporation of solute along with solvent in the detector.     

热敏荧光法用于蒸发液滴近接触线的温度测量

探究静置液滴蒸发的动力学原理在众多的相关工业应用中举足轻重。在过去的数十年间,尽管相关领域的学者进行了大量的研究工作,但仍有一个关键的问题尚未解决,即液滴接触线附近的温度在蒸发过程中到底是如何变化的。通过直接测量的实验方法,报道了液滴在接触线固定不动的蒸发阶段,其接触线附近温度的详细变化过程。利用显微热敏荧光测温技术,其结果表明：液滴接触线附近自由界面的温度将沿径向发生急剧变化,并伴随一组在蒸发过程中不断发生演变的荧光同心圆环,这种荧光条纹带是由于液滴边缘的几何差异性所导致的局部强化蒸发冷却与一组热浮力驱动的对流辊相互作用产生的结果。本研究将为蒸发动力学提供新的认识,并有望在各种对传热系统的应用领域中促成新的进展。     

Nanoparticle formation through solid‐fed flame synthesis: Experiment and modeling

The preparation of silica nanoparticles through solid‐fed flame synthesis was investigated experimentally and theoretically. Monodispersed submicrometer‐ and micrometer‐sized silica powders were selected as solid precursors for feeding into a flame reactor. The effects of flame temperature, residence time, and precursor particle size were investigated systematically. Silica nanoparticles were formed by the nucleation, coagulation, and surface growth of the generated silica vapors due to the solid precursor evaporation. Numerical modeling was conducted to describe the mechanism of nanoparticle formation. Evaporation of the initial silica particles was considered in the modeling, accounting for its size evolution. Simultaneous mass transfer modeling due to the silica evaporation was solved in combination with a general dynamics equation solution. The modeling and experimental results were in agreement. Both results showed that the methane flow rate, carrier gas flow rate, and initial particle size influenced the effectiveness of nanoparticle formation in solid‐fed flame synthesis. © 2009 American Institute of Chemical Engineers AIChE J, 2009