Supercritical CO2 based processing of amorphous fluoropolymer Teflon-AF: Surfactant-free dispersions and superhydrophobic films

We report the application of a modified RESS process to create and collect in high yield nanoparticles of an amorphous fluoropolymer, Teflon-AF1600. The nanoparticles with diameters ranging from 10 to 100 nm can be synthesized from polymer solutions in supercritical CO₂ at 300 bar and 60 °C. The nanoparticles are collected by formation of dry ice in a liquid nitrogen-cooled trap. Nanoparticles embedded in dry-ice can be dispersed in organic solvents (acetone, ethanol, and n-heptane) creating surfactant-free dispersions. When dispersed in water, the nanoparticles self-assemble at the air–water interface forming a mechanically robust, superhydrophobic film. The film can support large water droplets (up to volume 250 μL) without breaking and is impermeable to water. The films cast from dispersions as well as those lifted-off water surface, are highly porous and superhydrophobic in nature (water contact angle θ_adv = 162°). This work demonstrates the utility of supercritical fluids based processing of fluoropolymers.     

Particle size design of digitoxin in supercritical fluids

Bioavailability of the pharmaceutical substances is very important for their activity. In case of necessity, bioavailability can be improved by reducing the particle size of the drugs. In this study, particle size of digitoxin was reduced by the Rapid Expansion of Supercritical Solutions (RESS). The effects of pre-expansion temperature (90-110 °C), flow rate (2.5-7.5 ml/min), spray distance (3-7 cm) on the size and size distribution of the precipitated digitoxin particles were carried out. The particles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and LC-MS analysis.While the particle size range of the original digitoxin was 0.2-8 μm, it was decreased to 68-458 nm and determined that 97% of the particles were below 200 nm depending on the different experimental conditions.Response surface method (RSM) was used to optimize the process parameters. The flow rate, 7 ml/min; spray distance, 7 cm; pre-expansion temperature, 95 °C were found to be the optimum conditions to achieve the minimum particle size of digitoxin.     

Fabrication of fine microcapsulated red phosphorus particles by SCF-RESS with a new structure nozzle

A novel process of preparing microencapsulated red phosphorus particles by rapid expansion of supercritical fluids (RESS) was tested, in which a new kind of nozzle and supercritical CO₂ as a solvent were used. The structure of the microencapsulated red phosphorus particles were characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM). These results show that red phosphorus particles can be effectively encapsulated with paraffin by using the method. At the same time, how the moisture absorption ratio of microencapsulated red phosphorus particles was dependent on the experimental conditions was further investigated. The results suggest that paraffin-microencapsulated red phosphorus particles show a lower moisture absorption ratio within the experimental conditions of the extraction column and nozzle temperature of 120°C, extraction column pressure of more than 16 MPa, and a mass flow of core particles (0.5 g/min).     

Insulin and Insulin–Tripalmitin Particles Produced by a Supercritical Assisted Drying Process

A supercritical assisted drying (SAD) process was employed to produce insulin submicroparticles from an ethanol/water solution. The effect of the processing conditions on the morphology, size, and thermodynamic activity of the produced particles was investigated. Insulin particles generated from the process were generally spherical with average sizes between 0.4 and 1.1 µm. FTIR, HPLC, the Lowry method, and DTA–TG were implemented to investigate the thermodynamic activity and solvent residue of the produced particles. Results showed that the ethanol content of the aqueous solution had a more sensitive effect on the thermodynamic activity of the insulin particles than other operating factors; a high content of ethanol tended to denature the insulin particles. A rapid expansion of supercritical solutions (RESS)–SAD combined process was proposed to produce insulin–tripalmitin composite particles. Results indicated that irregular composite particles with insulin content of 33.1%, having a bimodal particle size distribution with two peaks at 3.5 and 11.0 µm, were obtained at 50.0°C and 12.0 MPa. These particles revealed no initial burst with a sustained release of insulin of more than 400 min.     

Preparation of submicron-sized RDX particles by rapid expansion of solution using compressed liquid dimethyl ether

Cyclotrimethylenetrinitramine (RDX) was precipitated to submicron-sized particles with spherical morphology by the rapid expansion from supercritical solution (RESS). Compressed liquid dimethyl ether (DME) was used as a solvent for the RDX. This study examined the influence of extraction temperature (293-333 K), extraction pressure (8-20 MPa) and size of orifice nozzle (50, 100, 200, and 250 μm) on the size and morphology of the RDX particles in the RESS process. The precipitated RDX particles were characterized by using the following instruments: field emission scanning electron microscope (FE-SEM), image analyzer, powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and differential scanning calorimetry (DSC). The precipitated RDX particles showed granular and spherical morphologies, submicron-sized particles, and narrow particle size distributions. The mean particle size of the precipitated RDX ranged from 2.48 to 0.36 μm, and the crystallinity of the precipitated RDX decreased. The enthalpy change for the exothermic decomposition of the precipitated RDX (ΔH = 714.4 J/g) was much higher than that of the original RDX (ΔH = 381.5 J/g).     

RESS技术在无机粉体制备中的应用

超临界流体快速膨胀法(RESS)制备无机粉体是近年来发展起来的一种极具应用前景的粉体制备新方法。笔者介绍了超临界流体的特性、RESS技术及其影响因素，总结了RESS技术在无机粉体制备方面的应用。     

新型超临界流体抗溶剂法制备超微颗粒的喷嘴设计

设计了一种新型旋转式压力喷嘴,该新型喷嘴利用切线入口和旋转室使料液充分混合并加速,最终雾化以更好地实现SEDS法制备超细颗粒的工艺。同时给出了针对不同物料时计算平均雾滴直径的公式,可以在实验前预估所制备超微颗粒的数量级,并对新型喷嘴结构对雾滴直径的影响因素做了分析。     

超临界流体快速膨胀法制备超细微粒

超临界流体快速膨胀法（RESS）是一项近10年发展起来的制备超细微粒的新技术,它将溶解有饱和溶质的超临界流体在非常短的时间内（10^-8-10^-5s)通过一个喷嘴（25－60um)进行减压膨胀,利用强烈的机械扰动以达到极高的过饱和度（约10^6)和均相成核条件,从而产生纳米至微米级粒径且粒径及形态分布均匀的超细微粒,该方法已经在制备药物微粒,聚合物微粒和纤维,有机材料和无机材料与陶瓷先驱物等方面得到广泛的应用研究,不仅可以制备单组分的形态不同的微粒或纤维,还可以制备双组分的包覆型微粒,但理论研究目前还处于探索阶段,不能准确解释装置结构参数和操作条件对最终产物形态的影响,在此主要就超临界流体的性质,RESS方法的基本原理,理论和应用研究成果进行简单介绍。     

Preparation and Characterization of Micronized Artemisinin via a Rapid Expansion of Supercritical Solutions (RESS) Method

The particle sizes of pharmaceutical substances are important for their bioavailability. Bioavailability can be improved by reducing the particle size of the drug. In this study, artemisinin was micronized by the rapid expansion of supercritical solutions (RESS). The particle size of the unprocessed white needle-like artemisinin particles was 30 to 1200 μm. The optimum micronization conditions are determined as follows: extraction temperature of 62 °C, extraction pressure of 25 MPa, precipitation temperature 45 °C and nozzle diameter of 1000 μm. Under the optimum conditions, micronized artemisinin with a (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA), extraction temperature and pressure have significant effects on the MPS of the micronized artemisinin. The particle size of micronized artemisinin decreased with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS, FTIR, DSC and XRD allowed the comparison between the crystalline initial state and the micronization particles obtained after the RESS process. The results showed that RESS process has not induced degradation of artemisinin and that processed artemisinin particles have lower crystallinity and melting point. The bulk density of artemisinin was determined before and after RESS process and the obtained results showed that it passes from an initial density of 0.554 to 0.128 g·cm(-3) after the processing. The decrease in bulk density of the micronized powder can increase the liquidity of drug particles when they are applied for medicinal preparations. These results suggest micronized powder of artemisinin can be of great potential in drug delivery systems.     

Preparation of anthracene fine particles by rapid expansion of a supercritical solution process utilizing supercritical CO<Subscript>2</Subscript>

The rapid expansion of a supercritical solution (RESS) process is an attractive technology for the production of small, uniform and solvent-free particles of low vapor pressure solutes. The RESS containing a nonvolatile solute leads to loss of solvent power by the fast expansion of the supercritical solution through an adequate nozzle, which can cause solute precipitation. A dynamic flow apparatus was used to perform RESS studies for the preparation of fine anthracene particles in pure carbon dioxide over a pressure range of 150–250 bar, an extraction temperature range of 50–70 °C, and a pre-expansion temperature range of 70–300 °C. To obtain fine particles, 100, 200 and 300 μm nozzles were used to disperse the solution inside of the crystallizer. Both average particle size and particle size distribution (PSD) were dependent on the extraction pressure and the pre-expansion temperature, whereas extractor temperature did not exert any significant effect. Smaller particles were produced with increasing extraction pressure and preexpansion temperature. In addition, the smaller the nozzle diameter, the smaller the particles and the narrower the PSD obtained.     

快速膨胀超临界溶液法制备α-细辛醚微细颗粒研究

用快速膨胀超临界溶液 (RESS)法获得了α 细辛醚的微细颗粒。考察了膨胀压力、膨胀前温度、沉降室温度、喷嘴直径等工艺条件对微细颗粒粒径的影响。结果表明 ,采用较高的膨胀压力 ,较低的膨胀前温度及沉降室温度 ,较小的喷嘴直径 ,有利于获得平均粒径较小的微细颗粒     

Formation of ultrafine aspirin particles through rapid expansion of supercritical solutions (RESS)

The performance of pharmaceuticals in biological systems can be enhanced by reducing the particle size of pharmaceuticals. Rapid expansion from supercritical solution (RESS) has provided a promising alternative to comminute contaminant-free particles of heat-sensitive materials such as drugs. In this work, aspirin has been successfully precipitated by the RESS technology. The performances of the RESS process under different operating conditions are evaluated through the analysis of the particle characteristics. Our results show that extraction pressure and extraction temperature can significantly affect the morphology and size of the precipitated particles whereas the nozzle diameter and pre-expansion temperature are not observed to apparently influence the RESS particles. The RESS process could produce ultrafine spherical particles (0.1-0.3 μm) of aspirin as reflected by SEM observations.     

Effects of extraction temperature, extraction pressure and nozzle diameter on micronization of cholesterol by RESS process

Micronized cholesterol particles were produced via the Rapid Expansion of Supercritical CO₂ Solutions (RESS) process. Taguchi design was used for designing the experimental plan to investigate the effects of three parameters including extraction temperature (40-60 °C), extraction pressure (100-160 bar) and nozzle diameter (0.15-0.24 mm) on the size and morphology of the cholesterol particles produced by the RESS process. The characterization of the particles was carried out using scanning electron microscopy (SEM) and X-ray diffraction (XRD) measurements to evaluate the performance of RESS process. The average particle size of the original material was 55 μm ± (2.84) while the average particle size of cholesterol after size reduction via the RESS process was between the minimum of 0.62 μm ± (0.03) and the maximum of 4.83 μm ± (0.18) depending upon the experimental conditions used. It was observed that both increasing the temperature from 40 to 60 °C and increasing the nozzle diameter from 0.15 to 0.24 mm result a reducing effect on the average particle size, whereas extraction pressure (100-160 bar) change has slight effect on the average particle size.