超临界流体快速膨胀法制备超细氟比洛芬粒子

文章选用二氧化碳作为超临界溶剂,采用超临界溶液快速膨胀技术制备超细氟比洛芬药物粒子,在较宽的温度压力范围内测定了氟比洛芬在超临界二氧化碳中的溶解度,考察了各种操作参数对药物粒子粒径的影响,研究了药物粒子粒径随各种操作参数的变化规律。结果表明：在实验考察的范围内,氟比洛芬的溶解度较小,在10-5~10-7之间（摩尔分率）,溶解度随着温度和压力的升高而增大。同时实验结果表明：粒径随预膨胀压力的升高而减小;一定范围内随接收距离的增大而增大;在萃取温度较低的情况下,粒子粒径基本随着萃取温度的升高而减小;随着萃取温度的升高,在相对较高预膨胀温度下,粒径随着萃取温度升高而增大。     

超临界流体快速膨胀法制备超细阿昔洛韦粒子

以二氧化碳作为超临界溶剂,采用超临界溶液快速膨胀技术制备得到超细阿昔洛韦药物粒子,在一定的温度和压力情况下,测定了阿昔洛韦在超临界二氧化碳中的溶解度,考察了各种操作参数对药物粒子粒径的影响,研究了药物粒子粒径随各种操作参数的变化规律。结果表明:阿昔洛韦在超临界二氧化碳中的溶解度较小,在10-5~10-6之间(摩尔分率),溶解度随着温度和压力的升高而增大,不存在文献中所报道的反向区。同时实验结果表明:药物粒子粒径变化对预膨胀温度最敏感,粒径随预膨胀温度的升高而减小;一定范围内随收集距离的增大而增大;在萃取温度较低的情况下,粒子粒径基本随着萃取温度的升高而减小;随着萃取温度的升高,在相对较高预膨胀温度下,粒径随着萃取温度升高而增大。     

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。     

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。     

RESS过程及其用于微细颗粒制备研究综述

介绍了超临界流体快速膨胀过程的主要特征，对超临界流体快速膨胀过程及用于微细颗粒制备的研究进行了综述,评析了文献对RESS过程制备微细颗粒的影响因素和对RESS过程机理模型的研究，阐述了RESS过程在不同体系下的应用研究。     

超临界快速膨胀技术制备超细聚苯乙烯

以丙烷为超临界溶剂，运用超临界溶液快速膨胀技术成功制得了微米级聚苯乙烯微粒，并考察了超临界溶液快速膨胀过程中溶液浓度、预膨胀温度、喷嘴结构和接收距离等对微粒粒径的影响。结果表明：制得的微粒形态良好、粒径分布较窄；当其它操作条件保持不变时，增加溶液浓度、降低预膨胀温度、增大喷嘴直径、减小喷嘴长度以及降低样品收集距离，都能有效地降低粒径。     

超临界溶液快速膨胀技术在微细粒子制备上的应用

超临界流体快速膨胀法 (RESS)是近 1 0年发展起来的一项制备超细粒子的新技术 ,可生产粒径达到纳米至微米级且粒径和形态分布均匀的超细粒子。虽然理论研究目前还处于探索阶段 ,但该方法已经在很多领域展示了诱人的应用前景。就近年来超临界溶液快速膨胀技术的原理、典型的实验装置、工艺特点和应用研究成果进行了扼要的论述     

用含夹带剂丙酮的超临界CO2快速膨胀法制备灰黄霉素的微细颗粒

Griseofulvin (GF) is an antifungal drug whose pharmaceutical activity can be improved by reducing particle size. In this study the rapid expansion of supercritical solution (RESS) was employed to micronize GF.Carbon dioxide with cosolvent acetone was chosen as a supercritical mixed solvent. The solubility of GF in super-critical CO2 with cosolvent acetone was measured using a dynamic apparatus at pressures between 12 and 32 MPa,temperatures at 313, 323 and 333 K and cosolvent concentration at 1.5, 3.0, 4.5 and 6.0% (by mole). The effect of pre-expansion pressure, extraction temperature, spraying distance, nozzle size and concentration of cosolvent on the precipitated particles was investigated. The results show that the mean particle size of griseofulvin precipitated by RESS was less than 1.2μm. An increase in pre-expansion pressure, extraction temperature, spraying distance and concentration of cosolvent resulted in a decrease in particle size under the operating condition studied. With the decrease of nozzle diameter the particle size reduces. The crystallinity and melting point of the original material and the processed particle by RESS were tested by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).No evident modification in the crystal habit was found under the experimental conditions tested. The morphology of particles precipitated was analyzed bY scanning electron microscopy (SEM).     

超细TiO_2粒子的溶胶凝胶法制备研究

用溶胶凝胶法制备了不同性状的超细TiO2粒子,研究了影响产物性能的主要因素。结果表明,通过对体系pH值、酯醇比、烧结温度等因素的控制,可制得所需要的TiO2超细粒子。     

超临界CO2快速膨胀法制备SiO2/聚氨酯超疏水涂层

用超临界CO₂快速膨胀法制备了SiO₂/聚氨酯超疏水涂层。首先用十三氟辛基三乙氧基硅烷（F-硅烷）和γ-(甲基丙烯酰氧基)丙基三甲氧基硅烷（KH-570）改性纳米二氧化硅,制备出含双键的纳米二氧化硅粒子,将其分散在超临界CO₂中,再利用超临界CO₂快速膨胀法将其喷射到双键封端的且已添加了引发剂的聚氨酯涂层表面,通过加热,使纳米二氧化硅粒子接枝在聚氨酯涂层表面,形成稳固粗糙结构,获得了超疏水性质。研究了喷嘴温度、反应釜温度和压力、偶联剂配比、表面粗糙度对涂层疏水性的影响。结果表明：涂层的静态水接触角可达到169.1°±0.6°;在喷嘴和釜内温度都为90℃,釜内压力为16 MPa,F-硅烷和KH-570配比为1∶1,表面粗糙度为7.3 μm时,所制得涂层具有较好的超疏水性,且具有优良的耐刮伤性。该法高效环保,涂层性能优良,适于大面积制备。     

超临界反溶剂过程制备灰黄霉素超细微粒

超临界反溶剂过程(SAS)是近年来提出的一种制备纳微米粉体的新方法。通过一套超临界反溶剂过程间歇式实验装置,以灰黄霉素、丙酮和二氧化碳系统为研究对象,实验研究了SAS过程参数对制备的微粒形态及其尺寸的影响。当操作条件为10 MPa,40℃,溶液浓度13.3 mg/mL和溶液流速1.5 mL/min时,制备了较为理想的灰黄霉素微粒,粒径分布均匀、形状基本呈球状;当8 MPa,42℃,溶液浓度15 mg/mL和溶液流速4.0 mL/min时,微粒粒径分布比较均一、主要呈细小针状。研究结果表明:采用丙酮作为有机溶剂,可制备出不同大小和形态的灰黄霉素超细微粒。这为改变灰黄霉素传统制剂做了前期准备工作,为制成可持缓释药物提供了可能性。     

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.     

Production of Nanocrystalline RDX by Rapid Expansion of Supercritical Solutions

Nanoscale crystals of cyclotrimethylenetrinitramine (RDX) were produced by Rapid Expansion of Supercritical Solutions (RESS). The experiments were performed by expansion of supercritical solutions of RDX in carbon dioxide through sapphire nozzles (ID: 100 and 150 μm) at pressures of 15.0–29.5 MPa and temperatures of 343–348 K. Recrystallized particles were characterized by Field Emission Scanning Electron Microscopy (FESEM), X‐ray diffraction, HPLC and melting point analysis. The process produced particles with a mean size in the range 110–220 nm and a narrow size distribution. The product was crystalline as determined by X‐ray diffraction. The effect of process conditions (T, P, nozzle diameter) on the crystal size distribution was determined.     

萘油组分的超临界萃取工艺研究

以乙醇为超临界萃取剂,利用恒容升温法对綦油组分中的萘、苊和芴进行超临界萃取工艺研究,对萃余液进行气相色谱检测,通过差量法计算其萃取率和超临界浓度,结果表明,超临界乙醇对萘油组分的萃取具有较好的效果,在萃取温度为270℃、萃取压力为13MPa时,萃取效果最好;萘、苊、芴3种物质超临界萃取规律明显;萘油组分的超临界乙醇萃取工艺绿色环保,切实可行。     

超临界状态下微胶囊化综述

综述了近年来在超临界溶液快速膨胀过程(RESS和气体抗溶剂法(GAS)基础上拓展出的微胶囊化方法,并设想和展望了超临界萃取和微胶囊化的耦合过程。     

超临界溶液快速膨胀过程中喷嘴的流动模型

本文基于超临界流体的特性,在一维定常可压缩流动的基础上,结合对流传热建立了超临界溶液快速膨胀过程（ＲＥＳＳ）的计算模型。该模型将ＲＥＳＳ过程喷嘴内的流动分为等熵节流和一维定常可管流两个部分,利用该模型可ＲＥＳＳ过程中喷嘴内部的流动,为研究ＲＥＳＳ过程提供基础。     

Micronization of creatine monohydrate via Rapid Expansion of Supercritical Solution (RESS)

In the pharmaceutical industry, an even greater number of products are in the form of particulate solids. In the case of pharmaceutical substances the particle size is quite important since it can limit the bioavailability of poorly water soluble drugs. Since the mid-1980s, a new method of powder generation has appeared involving crystallization with supercritical fluids. In this study, RESS was used to micronize the creatine monohydrate particles. The RESS process consists in solvating the product in the fluid and rapidly depressurizing this solution through an adequate nozzle, causing an extremely rapid nucleation of the product into a highly dispersed material. In addition, the effect of six different RESS parameters including, extraction temperature (313-333 K), extraction pressure (140-220 bar), nozzle length (2-15 mm), effective nozzle diameter (450-1700 μm), spraying distance (1-7 cm) and pre-expansion temperature (353-393 K) were investigated on the size and morphology of the precipitated particles of creatine monohydrate. The characterization (size and morphology) of the precipitated particles of creatine monohydrate was determined by scanning electron microscopy (SEM). The results show great reduction in the size of the precipitated particles of creatine monohydrate (0.36-9.06 μm) compared with the original particles of creatine monohydrate. Moreover, a slight change into spherical form was observed for the precipitated particles of creatine monohydrate while the original particles were irregular in shape.