基于超临界流体抗溶剂原理的造粒技术及其装置研究进展

超临界抗溶剂造粒技术由于具有操作条件温和、制得的微粒有机溶剂残留少、微粒粒径和形态可控等优点,已广泛地应用于药物运输体系的研究当中。本文简要介绍了超临界抗溶剂造粒技术的基本原理、装置组成和基本分类;从技术发展、喷嘴改进、技术结合、产品收集等方面,详细阐述了GAS、ASES、SEDS、SEDS-PA、SpEDS、SAS-EM、SAS-IJ、连续式RESS以及RESAS等基于超临界流体抗溶剂原理的造粒技术及其装置的改进过程;然后对目前其中存在的颗粒团聚、产品收集难和装置资源没有充分利用等问题提出了可能的解决方案;最后从数学模型的建立和规模化两方面,对超临界抗溶剂造粒技术基础理论的完善及其装置的改进进行了展望。     

超临界抗溶剂沉析技术

概述了超临界抗溶剂 (SAS)沉析技术的原理、过程和影响因素以及在制备微细颗粒和分级分离方面的应用。在制备微细颗粒方面 ,介绍了在含能材料、聚合物、药用化合物、染料、超导体、催化剂和无机盐等领域的主要应用 ;在分级分离方面 ,着重介绍了从发酵液中分级分离柠檬酸的新工艺、从牛奶中直接沉析酪蛋白和从混合DMSO溶液中结晶分离BaCl2 和NH4 Cl的探索 ,阐明了SAS技术存在的问题和发展的趋势     

超临界二氧化碳抗溶剂法在药物微胶囊化方面的应用

超临界二氧化碳抗溶剂法是制备微胶囊的新方法。简要叙述了超临界流体的特点,论述了微胶囊化技术的发展,着重介绍了抗溶剂法的特点,并总结出了操作过程中各参数的影响,同时对近期国内外这一领域的研究报道进行了综述,最后指出了应用中出现的问题及发展前景。     

超临界抗溶剂技术及其在药物方面的应用

介绍了超临界抗溶剂的原理,分析了工艺条件对粒子尺寸和尺寸分布的影响,着重说明了其在药物方面的应用。最后指出超临界抗溶剂技术的研究现状和应用前景。     

超临界抗溶剂技术制备缓释胶囊的研究进展

介绍了超临界抗溶剂技术制备缓释胶囊的原理、方法及研究进展,分析了颗粒性质的影响因素,总结了超临界抗溶剂技术在制备缓释胶囊方面存在的问题及展望。     

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CO2抗溶剂法制备聚苯乙烯微颗粒

进行了超临界CO2抗溶剂法制备聚苯乙烯微颗粒的实验.同时输入聚苯乙烯甲苯溶液和超临界CO2,连续操作30min,研究了不同二氧化碳和甲苯的流量比对聚苯乙烯结晶形态的影响.本实验条件下,二氧化碳和甲苯的流量比Wco2:Vsol≥36 g/ml时,才能生成离散的聚苯乙烯微颗粒.并利用抗溶剂法的原理,讨论了出现各种实验现象的原因.     

超临界抗溶剂法制备微粒的机理研究

超临界抗溶剂法是一种新型环保、具有广阔应用前景的微细颗粒制备技术,在材料科学、食品工业及药物微粒制备方面的应用成为研究的热点。随着实验研究中众多问题的出现,其理论研究越来越被重视,并且取得了一定的进展。着重从体系相平衡及溶液和超临界CO2之间的混合行为等方面,综述了近年来国内外对超临界抗溶剂法制备微细颗粒过程的理论研究进展并分析了部分存在问题。     

超临界流体抗溶剂技术及微粒成形机理的研究进展

超临界抗溶剂技术是一种新型的超细微粒制备技术,在药物、超导、颜料、炸药和聚合物等领域已有广泛的应用。本文主要介绍了超临界抗溶剂过程和该技术在单组分和多组分无机氧化物纳米粒子制备上的应用,并对超临界抗溶剂微粒成形机理的研究现状和微粒的成形机理进行了简要的概括总结。最后对超临界抗溶剂微粒化技术的发展做了进一步展望。     

超临界抗溶剂技术在药物微粒化领域的研究进展

总结了超临界抗溶剂技术在微粉化药物和制备缓释药物微球方面的研究现状和发展。在药物微粉化方面,着重介绍了超临界辅助原子化法对水溶性药物的处理,包括该方法的原理、操作方法以及操作参数对产品性能的影响,证明该方法用于改善水溶性药物的微粉化具有良好的效果;在制备药物微球方面,重点介绍了不同操作条件和不同分子质量的载体、不同配比的复合载体对药物微球性能的影响以及表面活性剂在亲脂性及离子型药物微球制备中的应用,指出添加表面活性剂将更有利于得到该类药物的微球。     

Micronization of curcumin with biodegradable polymer by supercritical anti-solvent using micro swirl mixer

Curcumin is a hydrophobic polyphenol compound exhibiting a wide range of biological activities such as anti-inflammatory, anti-bacterial, anti-fungal, anti-carcinogenic, anti-human immunodeficiency virus, and anti-microbial activity. In this work, a swirl mixer was employed to produce the micronized curcumin with polyvinylpyrrolidone (PVP) by the supercritical anti-solvent process to improve the bioavailability of curcumin. The effects of operating parameters such as curcumin/PVP ratio, feed concentration, temperature, pressure, and CO₂ flow rate were investigated. The characterization and solubility of particles were determined by using scanning electron microscopy, Fourier Transform Infrared spectroscopy, and ultra-violet-visible spectroscopy. The result shows that the optimal condition for the production of curcumin/PVP particles is at curcumin/PVP ratio of 1:30, feed concentration of 5 mg·mL⁻¹, temperature of 40 °C, pressure of 15 MPa, and CO₂ flow rate of 15 mL·min⁻¹. Moreover, the dissolution of curcumin/PVP particles is faster than that of raw curcumin.     

Micronization of arbutine using supercritical anti-solvent

Arbutine has been used as skin whitening agent in cosmetics and pharmaceuticals. The objective of this study was to precipitate arbutine micro-particles using a supercritical anti-solvent. Ethanol and supercritical CO₂ were used as solvent and anti-solvent, respectively, under various conditions. The effects of pressure, temperature and solution flow rate on the particles were studied. The particle size and morphology were analyzed by field emission scanning electron microscopy.     

Recrystallization of tetracycline hydrochloride using supercritical anti-solvent process

Tetracycline hydrochloride (TTC) was micronized by an Aerosol Solvent Extraction System (ASES) using supercritical CO₂. The effects of solvent, pressure and temperature of CO₂, solution concentration, and solution feed rate on particle size were investigated. Mean particle sizes of processed TTC were 0.16–0.31 μm, but the morphologies of processed particles were affected by agglomeration between the primary particles. Mean particle sizes of unprocessed TTC were ca. 200 μm and the shapes were irregular with rough surfaces. Especially, particle sizes increased from 0.18 to 0.31 μm as CO₂ temperature increased. In addition, particle sizes increased from 0.18 to 0.23 μm as TTC concentration increased. Powder X-Ray diffractometry revealed that processed particles were amorphous whereas unprocessed particles showed strong crystallinity.     

Preparation of liposomes using the supercritical anti-solvent (SAS) process and comparison with a conventional method

Two methods to produce liposomes encapsulating a fluorescent marker were compared: the supercritical anti-solvent (SAS) method and a conventional one (Bangham). Liposome size and encapsulation efficiency were measured to assess the methods. Micronized lecithin produced by the SAS process was characterized in terms of particle size, morphology and residual solvent content in order to investigate the influence of experimental parameters (pressure, CO₂/solvent molar ratio and solute concentration). It appears that when the lecithin concentration increases from 15 to 25 wt.%, at 9 MPa and 308 K, larger (20-60 μm) and less aggregated lecithin particles are formed. As concerns liposomes formed from SAS processed lecithin, size distribution curves are mainly bimodal, spreading in the range of 0.1-100 μm. Liposome encapsulation efficiencies are including between 10 and 20%. As concerns the Bangham method, more dispersed liposomes were formed; encapsulation efficiencies were about 20%, and problems of reproducibility have been raised.     

Effect of operating parameters on PVP/tadalafil solid dispersions prepared using supercritical anti-solvent process

Supercritical anti-solvent (SAS) process was employed to produce tadalafil solid dispersion sub-micron particles. Three independent variables for the SAS process (temperature, pressure, and drug concentration) were varied in order to investigate the effects on particle size and morphology of PVP/tadalafil solid dispersion (drug to polymer ratio 1:4). The mean particle size decreased with decreasing temperature (50 → 40 °C) and concentration (15 → 5 mg/mL) and increasing pressure (90 → 150 bar). Depending on the experimental variable, the mean particle size varied from 200 nm to 900 nm, and the dominant experimental variable was determined to be the drug concentration. Moreover, at a concentration of 15 mg/mL with any other process conditions, tadalafil tended to partially aggregate in crystalline form with irregular particle shapes. The results of in vitro dissolution experiments showed good correlation with mean particle size and crystallinity of the SAS-processed particles, in that the highest drug concentration showed the least dissolution rate and vice versa. Therefore, among the three variables studied, the drug concentration is the major factor that produces sub-micron particles in the SAS process.     

国外超临界水氧化技术的研究现状

超临界水氧化是水处理技术发展的新方向,但该技术对设备的要求比较高,工业化应用仍有一定的难度。为了克服这一难题,目前的研究工作主要集中在催化剂的选择以及设备防腐蚀等方面。介绍了贵金属类催化剂、过渡金属类催化剂、碱金属盐类催化剂、杂聚酸类催化剂以及碳基类催化剂,在降解不同污染物时的催化效率。在反应器材质和反应器形式的研究中,分别对铁、镊、铬等纯金属以及不同材料的合金在各种条件下的防腐蚀性能作了比较;两种最新的反应器形式:可蒸发壁式反应器和流动式反应器。它们在超临界水氧化中表现出了良好的防腐能力。     

Purification of algal anti-tyrosinase zeaxanthin from Nannochloropsis oculata using supercritical anti-solvent precipitation

This work investigated the changes in content of algal zeaxanthin in submicronized precipitates generated from the supercritical anti-solvent (SAS) process of extracting microalgae Nannochloropsis oculata. Following a reverse phase elution chromatography, the particulates were successfully generated from feed solutions containing zeaxanthin that ranged from 0.4 to 0.8 mg/mL by a SAS process. The precipitation condition was set at 323 K and pressures ranged from 10 to 20 MPa. Experimental results of a three-factor center composite response surface method for the SAS process indicated that the size of the precipitates was significantly affected by the flow rate of carbon dioxide. The purity of zeaxanthin increased with increasing solvent flow rate and with reducing solution concentration. The recovery of zeaxanthin and the morphology of the precipitates was also examined. The content of zeaxanthin in submicronsized precipitates increased from 485.9 (48.6%) to 673.7 mg/g (67.4%). This work demonstrates that elution chromatography coupled with a SAS process is an environmentally benign method to recover anti-tyrosinase zeaxanthin from Nannochloropsis oculata as well as to generate submicrosized precipitates of the purest zeaxanthin from algal solutions.     

应用超临界流体重结晶技术制备药物微粒

总结了超细药物微粒的常规制备方法,对超临界重结晶技术的两种常用方法,即超临界流体快速膨胀法和抗溶剂法进行了介绍,阐述了它们的应用进展情况,回顾了两种方法在国内中药药材领域的研究情况。并对超临界重结晶技术进行了展望,指出该技术为我国中药材有效成分的精细制备提供了一条富有前景的道路,但需要解决制备产量低、成本高、工艺和设备尚不完善等问题。