Fabrication of Micron Level Particles of Amoxicillin by Rapid Expansion of Supercritical Solution

In this study, the rapid expansion of supercritical solution (RESS) process was used to precipitate fine solid particles of amoxiccilin where supercritical carbon dioxide was used as a solvent. The process has been done by changing the RESS parameters, including extraction pressure (150–210 bar), extraction temperature (313–333 K), nozzle length (2–15 mm), effective nozzle diameter (450–1700 µm), and spraying distance (1–10 cm), to investigate the effect of these parameters on the size and morphology of the precipitated amoxicillin particles. The characterization (size and morphology) of the particles was examined using scanning electron microscopy (SEM). Based on the different experimental conditions, the mean particle size of the fabricated particles were between 1.08 and 5.72 µm, while the intact particles of amoxicillin were about 41.46 µm. Also, no regular changes in the morphology of the processed particles were observed.     

Thermal and morphological characterization of micronized acetylsalicylic acid powders prepared by rapid expansion of a supercritical solution

Aim of this work was to investigate the solid-state characteristics of micronized acetylsalicylic acid (ASA), produced by rapid expansion of a supercritical carbon dioxide solution (RESS) and to assess whether a correlation could be found between process parameters and solid-state characteristics. Drug solubility in supercritical CO₂ was first assessed under various pressure and temperature conditions. DSC, FT-IR, PXRD, SEM, laser light scattering and HPLC were used to characterise the solid phases produced by the RESS. The obtained particles were crystalline, with spectroscopical and diffractometrical pattern overlapping those of the starting available product. However, a strong reduction of particle size was obtained, linearly correlated to pressure imposed during the RESS process, while temperature did not seem to have a major effect. Similar influence of pressure was observed on the final melting temperature of the micronized ASA. The application of a mathematical model allowed to conclude that the melting temperature depression of RESS-prepared ASA powders can be attributed to the decrease of particle dimension rather than to the formation of different solid phases or impurities. This revised version was published online in July 2006 with corrections to the Cover Date.     

Solubility and micronisation of phenacetin in supercritical carbon dioxide

The rapid expansion of a supercritical solution (RESS) process represents an attractive prospect for producing sub-micron and nano-particles of medical compounds with low solubility. The solubility of phenacetin in supercritical carbon dioxide was measured by the analytical-isothermal method at pressures ranging from 9.0 MPa to 30.0 MPa and temperatures ranging from 308.0 K to 328.0 K. The results show that the mole fraction solubility of phenacetin in supercritical carbon dioxide is up to 10^?5. Four density-based semi-empirical models were introduced to correlate the experimental data. Agreement between the model predictions and experimental data is greater with the Adachi-Lu-modified Chrastil model than with the Chrastil model, Méndez-Santiago-Teja model, and the Bartle model and the average absolute relative deviation (AARD) observed is 0.0483. The preparation of fine phenacetin particles by the RESS process under different conditions of extraction temperatures (308.0–328.0 K), extraction pressures (9.0–30.0 MPa), nozzle temperatures (373.0–393.0 K), nozzle diameters (0.1–0.8 mm), and collection distance (20.0–40.0 mm) was investigated. The size and morphology of the resultant particles were analysed by SEM. A remarkable modification in size and morphology can be obtained by condition-optimisation.     

The formation of fluorinated tetraphenylporphyrin nanoparticles via rapid expansion processes: RESS vs RESOLV

Organic nanoparticles of a fluorinated tetraphenylporphyrin (TBTPP) were produced by rapid expansion of supercritical CO(2) solutions into both air (RESS) and an aqueous receiving solution containing a stabilizing agent (RESOLV). The effect of processing conditions on both particle size and form was investigated. The size of the porphyrin nanoparticles produced via RESS increased in a well-behaved manner from 40 to 80 nm as the preexpansion temperature increased from 40 to 100 degrees C, independent of porphyrin concentration, degree of saturation, and preexpansion pressure. RESOLV of TBTPP + CO(2) solutions was investigated both for minimizing particle growth in the free jet and for the prevention of particle agglomeration. Anionic, nonionic, and polymeric stabilizing agents for the aqueous receiving solution were considered. Expansion into a 0.05 wt % SDS solution produced nanorods 50-100 nm in diameter with an aspect ratio of 3-5. RESOLV in a 0.025 wt % Pluronic F68 solution produced well-dispersed, individual, spherical nanoparticles averaging 23 +/- 10 to 32 +/- 10 nm in diameter, independent of the rapid expansion processing conditions selected. Furthermore, the resulting nanoparticle suspensions were stable, with particle sizes remaining unchanged after several months. However, some particle agglomeration occurred at higher (i.e., 1 wt % TBTPP in CO(2)) concentrations. Contact-angle measurements on solid TBTPP compacts with the tested receiving solutions indicate that a moderate wetting agent such as Pluronic F68 is most effective for preserving the size and form of the porphyrin nanoparticles produced by RESOLV. Finally, the fact that nanoparticles are produced from RESS of TBTPP, in contrast with other organics for which microparticles are produced, can be explained in terms of the high melting point of TBTPP (388 degrees C), which results in a solid-state diffusion coefficient of TBTPP low enough so that particle coalescence is significantly reduced in the free jet.     

LIFAC烟气脱硫中应用蒸汽相变促进细颗粒物脱除的实验研究

在炉内喷钙尾部增湿活化(LIFAC)脱硫后的低温高湿烟气中添加适量蒸汽建立蒸汽相变所需的过饱和环境,促进水汽在细颗粒物表面凝结,进而由高效除雾器脱除凝结长大的含尘液滴.采用电称低压冲击器(ELPI)实时测定细颗粒物数量浓度及粒径分布,维萨拉温湿度变送器测试烟气温度和湿度.考察了活化水添加量、蒸汽添加量、细颗粒物数量浓度...     

Ultrafine agarose-coated superparamagnetic iron oxide nanoparticles (AC-SPIONs): a promising sorbent for drug delivery applications

A method for one-step synthesis of ultrafine agarose-coated superparamagnetic iron oxide nanoparticles (AC-SPIONs) was developed. The method is facile and fast and requires no organic solvent or surfactant. The average particle size of the prepared AC-SPIONs was only 20–40 nm with a narrow size distribution and with large saturation magnetization at room temperature. The obtained ultrafine nanogel particles were characterized by scanning electron microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, transmission electron microscopy and vibrating sample magnetometer techniques. The AC-SPIONs were epoxy-activated by epichlorohydrin and aminated by ammonium hydroxide. The amination of the particles was investigated by the Kaiser test. The adsorption of two model compounds (gallic acid and ellagic acid) on the functionalized nanoparticles and their releases from them were investigated spectrophotometrically in three different pH values under biological conditions. The functionalized AC-SPIONs displayed good adsorption and in vitro drug release in a phosphate-buffered saline (pH 7.4). The ultrafine AC-SPIONs can be potentially used in magnetic solid-phase extraction, drug delivery, protein purification and enzyme immobilization methods.     

Precipitation of Micronized Piroxicam Particles via RESS

In this study, the rapid expansion of supercritical solutions process was used to micronize the intact particles of piroxicam. Experiments were carried out to investigate the effect of extraction pressure (160–220 bar), extraction temperature (308–333 K), spraying distance (1–10 cm), and nozzle configuration (length and effective diameter) on the size and morphology of the precipitated piroxicam particle. The characterization of the particles was determined by scanning electron microscopy (SEM). The particle size of the original piroxicam particles was (39.2 µm) while depending upon the different experimental conditions, smaller particles of piroxicam (1.52–8.78 µm) were obtained.     

Effect of solvent type on the nanoparticle formation of atorvastatin calcium by the supercritical antisolvent process

The aims of this study were to identify how the solvent selection affects particle formation and to examine the effect of the initial drug solution concentration on mean particle size and particle size distribution in the supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was precipitated from seven different solvents using the SAS process. Particles with mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying organic solvent type and solution concentration. By changing the solvent, we observed large variations in particle size and particle size distribution, accompanied by different particle morphologies. Particles obtained from acetone and tetrahydrofuran (THF) were compact and spherical fine particles, whereas those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were agglomerated, with rough surfaces and relatively larger particle sizes. Interestingly, the mean particle size of atorvastatin calcium increased with an increase in the boiling point of the organic solvent used. Thus, for atorvastatin particle formation via the SAS process, particle size was determined mainly by evaporation of the organic solvent into the antisolvent phase. In addition, the mean particle size was increased with increasing drug solution concentration. In this study, from the aspects of particle size and solvent toxicity, acetone was the better organic solvent for controlling nanoparticle formation of atorvastatin calcium.     

Synthesis of size-controlled cobalt ferrite particles with high coercivity and squareness ratio

Cobalt ferrite particles with diameters ranging from a few micrometer to about 15 nm were synthesized using a modified oxidation process. The fine control of the particle size was achieved by introducing various concentrations of Fe(3+) ions at the beginning of the reaction. Among the particle sizes obtained by using this method, particles with a grain size of about 36 nm showed a magnetization (M(s)) of 64 emu/g and a maximum coercivity (H(c)) of 2020 Oe at room temperature. The corresponding squareness ratio was found to be 0.53.     

Low-temperature synthesis and microstructural control of titania nano-particles

Nanocrystalline titania powders were synthesized at low temperature (⩽100°C) by a sol–gel method that achieved fine control of particle size and polymorph fraction. X-ray diffraction (XRD), transmission electron microscopy (TEM) and UV–Vis spectroscopy were used to characterize the phase assemblages, crystal size and band gap of the powders. It was demonstrated that larger, well-ordered titania crystals can be obtained by increasing aging temperature and time. These processing parameters can be adjusted to select specific polymorphs from the gel precursors with particular size and shape. The quantum size effect was observed in the size-controlled nanocrystalline titania particles, leading to a blue shift in UV absorption with decreasing in particle size. The anatase to rutile transformation, which may proceed with brookite as a transition phase, is dependent on both particle size and surface structure of the nascent crystals.     

The generation of void morphology inside soap-free P(MMA-EA-MAA) particles prepared by seeded emulsion polymerization

Monodisperse soap-free P(MMA-EA-MAA) latex particles were synthesized by seeded emulsion polymerization of methyl methacrylate (MMA), ethyl acrylate (EA) and methacrylic acid (MAA), and the particles with void morphology were obtained after undergoing alkali post-treatment. Effects of treatment conditions on particle morphology were investigated. Results showed that the void particles can be obtained under the conditions of the temperature >60 degrees C, initial pH >10.0, treatment time >20 min and 2-butanone amount >2.0 ml. The particle volume and the void size increased to the maximum and then decreased with the increases of initial pH and the treatment time, and these two values increased monotonously with the treatment temperature or 2-butanone amount increased. When the treatment temperature was elevated to 90 degrees C, the treatment time was longer than 180 min, or the 2-butanone amount was more than 8.0 ml, the relatively small voids inside most of the particles combined together to form a large one. The void structure disappeared completely as the initial pH was higher than 12.0. The generation mechanism of the void morphology was discussed.     

Recovery of silver nanoparticles synthesized on AOT/C(12)E(4) mixed reverse micelles by antisolvent CO(2)

Silver nanoparticles were synthesized in sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles in isooctane with tetraethylene glycol dodecyl ether (C(12)E(4)) as a cosurfactant. Recovery of the Ag particles from the reverse micelles by dissolving antisolvent CO(2) in the micellar solution was investigated. All the Ag particles in the reverse micelles could be precipitated by compressed CO(2) at suitable pressures, while the surfactants remained in the isooctane continuous phase, and well-dispersed Ag nanoparticles were obtained. The effects of operating conditions on the size and size distribution of the Ag particles were investigated. The particle size decreased with decreasing molar ratio (w) of water to surfactant. A higher CO(2) pressure in the recovery process favored production of smaller particles. A decrease in the molar ratio of reductant KBH(4) to AgNO(3) resulted in larger Ag particles with higher polydispersity.     

Micronization of Iron Oxide Particles Using Gas Antisolvent Process

Iron oxide particles were micronized by supercritical carbon dioxide (CO₂) as an antisolvent in a batch gas antisolvent (GAS) process. In the present study, the feasibility of GAS process to micronize the iron oxide particles using dimethyl sulfoxide (DMSO) as a solvent was investigated. In this direction, particle size and morphology changes were investigated with changing solution pressure (80–150 bar), temperature (308.15–328.15 K), and concentration (1.5–6 g/l). Based on the different experimental conditions, the particle size of the original iron oxide was decreased in the range of 17.25 to 4.23 µm, which shows a the success of the GAS process to reduce the particle size of the intact iron oxide particles. Simultaneously, morphology changes were observed starting from the irregular morphology for synthesized particles to more regular shapes that included fused and spherical-fused particles.     

Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 μm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds.     

The self-preserving size distribution theory. I. Effects of the Knudsen number on aerosol agglomerate growth

Gas-phase synthesis of fine solid particles leads to fractal-like structures whose transport and light scattering properties differ from those of their spherical counterparts. Self-preserving size distribution theory provides a useful methodology for analyzing the asymptotic behavior of such systems. Apparent inconsistencies in previous treatments of the self-preserving size distributions in the free molecule regime are resolved. Integro-differential equations for fractal-like particles in the continuum and near continuum regimes are derived and used to calculate the self-preserving and quasi-self-preserving size distributions for agglomerates formed by Brownian coagulation. The results for the limiting case (the continuum regime) were compared with the results of other authors. For these cases the finite difference method was in good in agreement with previous calculations in the continuum regime. A new analysis of aerosol agglomeration for the entire Knudsen number range was developed and compared with a monodisperse model; Higher agglomeration rates were found for lower fractal dimensions, as expected from previous studies. Effects of fractal dimension, pressure, volume loading and temperature on agglomerate growth were investigated. The agglomeration rate can be reduced by decreasing volumetric loading or by increasing the pressure. In laminar flow, an increase in pressure can be used to control particle growth and polydispersity. For D(f)=2, an increase in pressure from 1 to 4 bar reduces the collision radius by about 30%. Varying the temperature has a much smaller effect on agglomerate coagulation.     

INFLUENCES OF ACID POST-TREATMENT ON THE MORPHOLOGY OF SOAPFREE P（MMA-EA-MAA） PARTICLES PREPARED BY SEEDED EMULSION POLYMERIZATION

Soap-free poly（methyl methacrylate-ethyl acrylate-methacrylic acid） latex particles with narrow size distribution were synthesized by seeded emulsion polymerization, and the porous particles were created by a stepwise alkali/acid treatment method. Effects of acid treatment conditions on the particle morphology were investigated. Results show that one to three pores were formed inside most of particles after post-treatment. At pH 7.0, when the treatment temperature was lower than 70℃, the size of particles and the volume of pores remained almost unchanged, and these two values increased significantly when the temperature was higher than 70℃. Both the particle size and the pore volume decreased with the increase of initial pH value and treatment time in the acid treatment. As the pH was below 4.0 and the treatment time was longer than 180 min, the particles shrunk in size.     

超临界流体沉淀技术制备超细粒子研究

超临界流体沉淀(简称SFP)技术以其特有的优点成为引人注目的在无机化学、有机化学、医药等领域具有广阔应用前景的超细微粒制备方法.为充分发挥SFP技术的优势,科研工作者以RESS与SAS为基础提出了ASES、SEDS、SAS-EM等各种新技术.本文着重综述了以RESS及SAS为基础发展起来的SFP新技术的原理、特点及相关的应用,指出了目前SFP技术存在的问题及今后的研究方向.     

Steric stabilization of thermally responsive N-isopropylacrylamide particles by poly(vinyl alcohol)

Poly(vinyl alcohol) (PVA) was used as a steric stabilizer for the dispersion polymerization of cross-linked poly(N-isopropylacrylamide) (PNIPAM) in water. A series of reactions were carried out using PVA of varying molecular weight and degree of hydrolysis. Under appropriate conditions, PNIPAM particles of uniform and controllable size were produced using PVA as the stabilizer. The colloidal stability was investigated by measuring changes in particle size with temperature in aqueous suspensions of varying ionic strength. For comparison, parallel colloidal stability measurements were conducted on PNIPAM particles synthesized with low-molecular-weight ionic surfactants. PVA provides colloidal stability over a wide range of temperature and ionic strength, whereas particles produced with ionic surfactants flocculate in moderate ionic strength solutions upon collapse of the hydrogel as the temperature is increased. Experimental results and theoretical consideration indicate that sterically stabilized PNIPAM particles resulted from the grafting of PVA to the PNIPAM particle surface. The enhanced colloidal stability afforded by PVA allows the temperature-responsive PNIPAM particles to be used under physiological conditions where electrostatic stability is ineffective.     

采用超临界CO_2萃取技术提取废次烟叶中的茄尼醇

采用超临界CO2萃取技术提取废次烟叶中的有效成分茄尼醇,以乙醇为夹带剂,研究了萃取压力、萃取温度、CO2的流量、萃取时间、夹带剂的使用、分离温度和原料粒度等方面对萃取效果的影响,并对其中影响较为显著的因素进行了正交试验,通过极差和方差分析确定了萃取体系适宜的工艺条件。萃取压力为20 MPa,萃取温度为45℃,CO2的流量为15 L/h,萃取时间为2 h,夹带剂为95%的乙醇,分离温度为40℃,原料粒度为40~60目。     

Electrokinetic Characterization of Poly(N-isopropylacrylamide) Microgel Particles: Effect of Electrolyte Concentration and Temperature

A fundamental study about the characterization of a poly(N-isopropylacrylamide), poly(NIPAM), microgel, cross-linked with N,N'-methylene bisacrylamide (BA), has been carried out. The anionic charge of this system was increased by copolymerization with 2-acrylamido-2methylpropanesulphonic (AMPS) acid. The electrokinetic behavior of these aMPS/NIPAM microgel particles has been investigated. First, the surface charge density was determined by conductimetric titration, and the particle size was obtained by transmission electron microscopy under several conditions. Electrophoretic mobility measurements were carried out as a function of electrolyte concentration and temperature. The hydrodynamic diameter of the particles was also measured by photon correlation spectroscopy as a function of electrolyte concentration and temperature. These size data have been taken into account in order to explain the mobility behavior by using Ohshima's theory for soft particles, with very good agreement between experiments and theoretical predictions. Copyright 2001 Academic Press.