超临界流体技术在制备药物输送系统中的应用

超临界流体技术以其特有的优点成为引人注目的制备药物细微粒子及控制释放的药物输送系统的方法。本文介绍了超临界流体沉淀技术的概念、进展及相关的应用。     

药用合成高分子缓、控释材料研究进展

药物的缓、控释材料可以实现药物的平稳长期的释放,同时使药物治疗达到有的放矢的效果,高分子材料是制作药物缓控释材料的重要材料,包括天然高分子与合成高分子两大类。其中,天然高分子用作药物缓控释材料的研究已有多年的历史,已为人们所熟知。本文主要综述药用合成高分子缓、控释材料研究进展,分析了不同缓、控释材料的制备方法、释药原理和适用药物,为合成新型药用缓、控释材料,扩大药用缓、控释高分子材料的应用范围提供依据。     

药用微胶囊的制备

微胶囊技术是21世纪重点研究开发的高新技术之一,用途广泛。本文综述了微胶囊的制备原理及方法,着重阐述了采用超临界二氧化碳技术和溶剂蒸发法制备药物微胶囊的最新研究进展,介绍了超临界流体快速膨胀(RESS)法、超临界流体抗溶剂(SAS)法和气体饱和溶液微粒制备(PGSS)法的特点,总结了溶剂蒸发法制备微胶囊的原理和溶剂蒸发法制备药物微胶囊的工艺研究现状,分析了药物微胶囊的表征方法及性能,并对今后微胶囊技术的发展作了展望。     

微胶囊技术在生物医药中的应用

综述了微胶囊的制备原理,介绍了微胶囊主要制备技术,包括超临界流体技术和溶剂蒸发法在制备药物微胶囊中的应用,并对以后微胶囊技术的发展作了展望.     

聚酸酐共聚物在药物缓控释领域中的研究进展

从聚酸酐共聚物的制备方法、性能结构、剂型工艺及其在缓控释领域的应用等方面综述了其研究成果,并对其在缓控释领域的应用前景进行了展望。     

超临界流体技术制备纳米材料的研究与展望

纳米科技是人们普遍关注的重要领域,而纳米材料充当其中的基础性角色。本文介绍了在新兴绿色环保介质——超临界流体中纳米材料的合成及其制备,涉及范围包括从准零纳米微粒到三维纳米材料,从无机纳米材料到有机聚合物纳米材料。其中不仅介绍了超临界流体中纳米材料的制备方法,同时也包括制备过程中超临界流体特殊性质,如溶胀、塑化和地表面张力所起的重要作用,并对超临界流体技术在纳米材料制备中的应用前景进行展望。     

超临界流体沉积技术在纳米复合材料制备中的应用*

本文综述了超临界流体沉积法在纳米复合材料制备领域的进展,介绍了利用超临界流体的溶剂化特性、表面张力为零、性质随压力与温度的变化敏感等性质,制备高质量的纳米粒子、薄膜及多孔纳米材料,讨论了超临界流体沉积过程中的吸附、热力学平衡及扩散动力学等问题,总结了不同学者对该方法制备复合材料的机理研究,认为超临界流体沉积法是制备纳米复合材料的有效方法。最后,对深入开展此项研究工作需要努力的方向和解决的关键问题提出了建议。     

反相液相制备色谱法结合超临界流体制备色谱法分离纯化海风藤中的化合物

建立了基于反相液相制备色谱和超临界流体制备色谱的组合方法,用于分离纯化醇提水沉后石油醚层中的海风藤。首先以甲醇作为改性剂,采用醇提水沉法去除海风藤甲醇提取物中的叶绿素,加入硅藻土后用石油醚回流富集目标成分。选用反相C18制备色谱柱将其分为18个组分,然后将组分在SFC模式下进行制备。选用酰胺色谱柱,以甲醇为改性剂,在柱温30℃、背压15.0 MPa的条件下进行分离。基于反相色谱和超临界流体色谱不同的分离选择性,最后分离得到6个高纯度化合物。该法展示了反相制备色谱和超临界流体制备色谱在海风藤分离纯化方面的优势,特别是超临界流体色谱在天然产物的分析和制备方面的巨大潜力。     

超临界CO2法制备头孢唑啉钠脂质体

采用超临界CO2(scCO2)流体代替有机溶剂一步法制备了头孢唑啉钠药物载体脂质体. 研究了该脂质体的尺寸、稳定性和药物的包封率. 结果表明, 脂质体的尺寸和稳定性依赖于制备压力, 脂质体对头孢唑啉钠的包封率与乙醇和脂浓度有关, 采用超临界CO2法制备脂质体的药物包封率比采用薄膜分散法(Bangham method)制备的包封率高.     

微粉化技术提高水不溶性药物溶解度

药物的微粉化可以改善颗粒的润湿性,进而提高水不溶性药物的溶解度和溶解速率。目前普遍采用的药物微粒化技术主要包括机械研磨、超临界流体过程、低温喷淋和溶剂蒸发沉积过程。本文介绍了这些微粉化制备技术的基本原理以及该类技术的应用进展。     

超临界流体萃取分离离子液体与有机物及其相平衡的研究

离子液体具有一些优良的物理和化学性质,非常有希望成为传统有机溶剂的替代溶剂.但是如何从过程物流中分离和回收离子液体将是其工业化应用的一个很大挑战.蒸馏、液液萃取和超临界萃取是目前已知的三个可行的方法.其中超临界萃取可应用于离子液体与挥发的或相对不挥发的有机物的分离,而且不存在相间交叉污染.本文从二元体系相平衡、三元体系相平衡、模型化研究和萃取实验结果方面介绍了超临界萃取方法的最新研究进展,在此基础上提出了用超临界丙烷替代超临界二氧化碳作为萃取溶剂的新思路,并探讨了该领域今后的研究方向和工业化前景.     

Applications of packed and capillary supercritical fluid chromatography in the separation of tocochromanols

Tocochromanols consisting of tocopherols and tocotrienols, is collectively known as vitamin E. Similarity in their structures, physical and chemical properties rendered the tocochromanols to be subject of chromatography interest. Supercritical fluid chromatography is a highly efficient tool for the separation and analysis of tocochromanols. Separation and analysis of tocochromanols using supercritical fluid chromatography had been carried out in the past using capillary or packed columns. Each of these techniques offer their own advantages and drawbacks. Besides being used for analysis, packed column supercritical fluid chromatography found applications as a purification and content enrichment tool. Emergence of new equipment and stationary phase technologies in recent years also helped in making supercritical fluid chromatography a highly efficient tool for the separation and analysis of tocochromanols. This paper gives an insight into the use of capillary and packed columns in supercritical fluid chromatography for the separation and/or analysis of tocochromanols. The types of stationary phase used, as well as chromatographic conditions are also discussed.     

On-line multidimensional supercritical fluid chromatography/capillary gas chromatography

A new analytical technique combining on-line supercritical fluid chromatography with capillary gas chromatography has been developed. The supercritical fluid sample effluent is decompressed through a restrictor directly into a conventional capillary gas chromatographic injection port. This technique allows for not only direct (100%) sample transfer from the supercritical fluid chromatograph to the gas chromatograph but also for selective or multi-step heartcutting of various sample peaks as they elute from the supercritical fluid chromatograph. Heartcut times are determined by monitoring the responses from the flame ionization or ultraviolet absorbance detectors on the supercritical fluid chromatograph. This report describes the operational setup and provides the results of heartcut reproducibility experiments using normal hydrocarbon and aromatic test mixtures. Results from studies where operational parameters were varied, such as GC injector temperature, will also be provided. The potential usefulness of this new technique for selective heartcutting will also be demonstrated using complex hydrocarbon streams.     

Analysis of new psychoactive substances in human urine by ultra‐high performance supercritical fluid and liquid chromatography: Validation and comparison

New psychoactive substances represent serious social and health problem as tens of new compounds are detected in Europe annually. They often show structural proximity or even isomerism, which complicates their analysis. Two methods based on ultra high performance supercritical fluid chromatography and ultra high performance liquid chromatography with mass spectrometric detection were validated and compared. A simple dilute‐filter‐and‐shoot protocol utilizing propan‐2‐ol or methanol for supercritical fluid or liquid chromatography, respectively, was proposed to detect and quantify 15 cathinones and phenethylamines in human urine. Both methods offered fast separation (<3 min) and short total analysis time. Precision was well <15% with a few exceptions in liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3 ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography. Nevertheless, this technique distinguished all analytes including four pairs of isomers, while liquid chromatography was unable to resolve fluoromethcathinone regioisomers. Concerning matrix effects and recoveries, supercritical fluid chromatography produced more uniform results for different compounds and at different concentration levels. This work demonstrates the performance and reliability of supercritical fluid chromatography and corroborates its applicability as an alternative tool for analysis of new psychoactive substances in biological matrixes.     

New Device for Adding Polar Modifiers to Carbon Dioxide Mobile Phase for Supercritical Fluid Chromatography

Abstract

Adding additional components to supercritical carbon dioxide in supercritical fluid chromatography can extend or significantly alter the fluid solvating properties. Polar samples which are difficult to be analyzed with pure supercritical CO₂ because of their high polarity can be separated by adding polar modifiers to supercritical CO₂. In this paper, a new mixing device using a teflon high capacity filter for adding polar modifiers to carbon dioxide mobile phase is introduced. This new mixing device could keep the amount of modifier in the mobile phase constant for a much longer time than a saturator column. The amount of water or methanol dissolved in supercritical CO₂ was measured by amperometric microsensor which is made of thin film of perfluorosulfonate ionomer(PFSI).     

Vibrational Spectroscopy in Supercritical Fluids: From Analysis and Hydrogen Bonding to Polymers and Synthesis

Supercritical fluids are beginning to be used widely in chemistry. Applications range from extraction and chromatography in analytical chemistry to solvents for reaction chemistry and preparation of new materials. Spectroscopic monitoring is important in much of supercritical chemistry, and vibrational spectroscopy is particularly useful in this context because the vibrational spectrum of a given molecule is usually quite sensitive to the environment of that molecule. Thus, vibrational spectra are excellent probes of conditions within the fluid. In this review, we describe a variety of techniques and cells for IR and Raman spectroscopy in supercritical fluids and illustrate the breadth of applications in supercritical fluids. The examples include: the use of supercritical Xe as a spectroscopically transparent solvent for chemistry and for supercritical fluid chromatography with FTIR detection of analytes; Raman spectroscopy as a monitor for gases dissolved in supercritical CO₂; the effect of solvent density on hydrogen bonding in supercritical fluids and the formation of reverse micelles; IR as a monitor for the supercritical impregnation/extraction of polymers and the reactions of organometallic compounds impreganated into polymers; reactions of organometallic compounds in supercritical fluids; and finally, the use of miniature flow reactors for laboratory-scale preparative chemistry. Overall, our aim is to provide a starting point from which individual readers can judge whether such measurements might usefully be applied to their own particular problems.     

New device for controlling the amount of methanol in carbon dioxide mobile phase for supercritical fluid chromatography

A new device to accurately deliver a small amount of methanol into supercritical carbon dioxide fluid is described. Carbon dioxide, the most widely used mobile phase in supercritical fluid chromatography, is a relatively non-polar fluid, and hence the addition of a small amount of methanol could change the solvent strength of the mobile phase. In this work, supercritical CO₂ and methanol are delivered from the pump to a 100-μl mixing chamber in which a small magnetic bar is rotating. After passing through the mixing chamber, supercritical CO₂ is changed to a new mobile phase with different polarity. The modified mobile phase was successfully used for the separations of polar compounds and polyaromatic hydrocarbons (PAHs).     

Comparison of two extraction methods independently developed on two conceptually different automated supercritical fluid extraction systems for the determination of polychlorinated biphenyls in sediments

Two extraction methods that independently have been developed on conceptually different automated supercritical fluid extraction systems, ISCO SFX 3560 (syringe pump and liquid trapping) and Hewlett-Packard 7680T SFE (reciprocating pump and solid-phase trapping), were compared for the extraction of polychlorinated biphenyls from two Swedish sediments. The results demonstrated that the high-temperature ISCO method in some cases yields a more exhaustive extraction, but also less clean extracts due to co-extraction of unwanted matrix components which are all present in the trapping solvent. The medium-temperature Hewlett-Packard method may sometimes cause problems with quantitative recoveries, but on the other hand it yields very clean extracts due to the extra selectivity resulting from collection on a solid-phase trap.     

Silica hydride intermediate for octadecylsilica and phenyl bonded phase preparation via heterogeneous hydrosilation in supercritical carbon dioxide

Investigations into the preparation of silica hydride intermediate in supercritical carbon dioxide (sc-CO(2)) that avoids the use of organic solvents such as toluene or dioxane are described. The effects of reaction temperature, pressure and time on the surface coverage of the supercritical fluid generated silica hydride intermediate were studied. Under optimised supercritical conditions of 120°C, 483 bar and 3 h reaction time, silica hydride (Si-H) conversion efficiencies of ca. 40% were achieved for the hydride intermediate prepared from a monofunctional silane reagent (dimethylmethoxysilane). Si-H conversion efficiencies (as determined from (29)Si CP-MAS NMR spectral analysis) for the hydride intermediate prepared from triethoxysilane (TES) in sc-CO(2) were found to be comparable to those obtained using a TES silanisation approach in an organic solvent. (13)C and (29)Si CP-MAS-NMR spectroscopy was employed to provide a complete structural assignment of the silica hydride intermediates. Furthermore, supercritical CO(2) was subsequently employed as a reaction medium for the heterogenous hydrosilation of silica hydride with octadecene and with styrene, in the presence of a free radical initiator. These supercritical fluid generated reversed-phase materials were prepared in a substantially reduced reaction time (3 h) compared to organic solvent based methods (100 h reaction time). Silica functionalisation in sc-CO(2) presents an efficient and clean alternative to organic solvent based methods for the preparation of important silica hydride intermediate and silica bonded stationary phases via a hydrosilation approach.     

Recent advances in sample introduction for supercritical fluid chromatography

New strategies for sample introduction in supercritical fluid chromatography are reviewed. Both open tubular and packed column systems are examined as the injection demands of each column type are addressed. In addition to advances made in solvent injection methods, supercritical fluid extraction (SFE) is discussed as a solventless injection technique for supercritical fluid chromatography.