超临界流体技术制备微粒的研究进展

目的：综述近年来超临界流体技术制备微粒的特点、分类、原理、方法及最新研究动态。方法：通过不同超临界流体技术方法比较，介绍该方法在药剂学中的应用特点。结果：超临界流体技术用于药物微粉化时，气化所需能量低，颗粒规则、均匀、晶型纯度高；在用于微球制备时，其粒径均匀，无有机溶媒残留，对药物的稳定性影响小，工艺重现性好。结论：超临界流体技术必将在药物微粉化和微球的制备方法上显示出其独特的优越性，其应用前景十分乐观。     

超临界流体沉降技术制备微粒的研究进展

本文简单介绍超临界流体的特性,阐述超临界流体沉降技术的种类和特点,综述近几年在纳米粒、微球和微囊制备方面的最新研究进展。     

超临界流体辅助雾化法制备抗生素微粒

超临界流体辅助雾化法(SAA)是一种新型的运用超临界流体来制备固体微粒的方法，可用于水溶性溶质的微粒制备，特别适用于药物行业。本文综述了SAA的特色、流程、操作条件和在抗生素中的应用情况。描述了所得微粒的平均粒径、粒子形状以及粒度分布曲线等。经SAA法加工后的药物微粒．未见质量降低，并符合气溶胶给药要求。目前SAA已进人中试阶段，具有较快的过程开发速度。     

超临界流体辅助雾化制备药物微粒的研究进展

超临界流体辅助雾化是一种制备药物微粒的新方法.本文介绍该法的原理与装置,并与其它超临界流体制粒技术进行了比较,并概述近年在制药领域中的研究进展.     

超临界流体技术在制备药物微粒中的影响因素

目的：介绍国内外超临界技术制备药物微粒的分类、原理、影响因素。方法：通过三种不同方法的介绍比较，综合介绍该方法的特点及制备过程中影响因素的改进。结果：利用超临界流体技术制备药物微粒．通过合理控制实验条件，可使能量消耗低、重现性好、粒度均匀、晶型稳定。结论：合理控制条件下超临界流体技术制备药物微粒有其优越性，值得推广应用。     

超临界流体强化溶液分散法制备L-聚乳酸微粒

利用超临界流体强化溶液分散法(SEDS法)制备了生物可降解L-聚乳酸(PLLA)微粒,研究不同压力、温度及溶液浓度条件下所制备微粒的大小、形态和分布情况.实验表明:微粒平均粒径为5～26μm,呈球形;微粒粒径和粒径分布随压力的升高而减小,随浓度的增大而增大,温度对微粒粒径的影响不显著.超临界体系中PLLA玻璃化转化温度的降低对微粒影响较大,使微粒粒径变大,粒径分布变宽.高压低温有利于产生粒径小且分布均匀的球形微粒.     

超临界流体技术在抗生素类药物微粒制备中的应用

综述了超临界流体技术在抗生素行业中的新研究成果和应用概况：不论在抗生素类药物微粒制备或在其提取工艺中都应重视溶解度的基础研究。着重介绍了超临界溶液快速膨胀和超临界抗溶剂工艺在抗生物微粒制备中的进展。所得实例显示出超临界流体技术在抗生索微粒制备中的潜在优势和进一步拓展其应用的良好前景。     

超临界流体技术试制阿莫西林缓释微粒

幽门螺杆菌对阿莫西林(1)极敏感.但1体内半衰期较短(约1.1h),经尿路排泄较快,影响了疗效[1],因此有必要将其制成缓释微粒.常用制备方法有液中干燥法、溶剂蒸发法等,也有采用超临界流体技术的报道.如Reverchon等[2]用超临界流体抗溶剂(SAS)法制得0.25～1.2um的1微粒(不具缓释效果),York等[3]用超临界流体增强溶液分散(solution enhanced dispersion by supercritical fluids,SEDS)技术制得对乙酰氨基酚、吲哚美辛等乙基纤维素(EC)微囊.     

超临界流体技术在药学领域制备微粒中的应用

超临界流体在体系中可分别作为溶剂、抗溶剂、溶质，本文综述了近年来超临界流体技术用于制备微粒（如纳米粒、微球、脂质体、固体分散体等）的装置原理、工艺以及在药学领域中的研究进展。     

超临界抗溶剂技术在药物微粒制备领域中的应用

超临界抗溶剂(SAS)技术是一种新型的微粒制备技术.本文介绍了SAS技术的基本原理和操作方式,综述了近年来SAS技术在药物微粒制备领域中包括制备药物超细微粒和药用复合微粒两个方面的应用,并展望了SAS技术在药物微粒制备领域中的主要研究前景.     

Nanoparticles of Poorly Water-Soluble Drugs Prepared by Supercritical Fluid Extraction of Emulsions

Purpose The aim of the study was to develop and evaluate a new method for the production of micro- and nanoparticles of poorly soluble drugs for drug delivery applications. Methods Fine particles of model compounds cholesterol acetate (CA), griseofulvin (GF), and megestrol acetate (MA) were produced by extraction of the internal phase of oil-in-water emulsions using supercritical carbon dioxide. The particles were obtained both in a batch or a continuous manner in the form of aqueous nanosuspensions. Precipitation of CA nanoparticles was used for conducting a mechanistic study on particle size control and scale-up. GF and MA nanoparticles were produced in several batches to compare their dissolution behavior with that of micronized materials. The physical analysis of the particles produced was performed using dynamic light scattering (particle size), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), gas chromatography (residual solvent), and a dissolution apparatus. Results Particles with mean volume diameter ranging between 100 and 1000 nm were consistently produced. The emulsion droplet size, drug solution concentration, and organic solvent content in the emulsion were the major parameters responsible for particle size control. Efficient and fast extraction, down to low parts-per-million levels, was achieved with supercritical CO₂. The GF and MA nanoparticles produced were crystalline in nature and exhibited a 5- to 10-fold increase in the dissolution rate compared with that of micronized powders. Theoretical calculations indicated that this dissolution was governed mainly by the surface kinetic coefficient and the specific surface area of the particles produced. It was observed that the necessary condition for a reliable and scalable process was the sufficient emulsion stability during the extraction time. Conclusion The method developed offers a viable alternative to both the milling and constructive nanoparticle formation processes. Although preparation of a stable emulsion can be a challenge for some drug molecules, the new technique significantly shortens the processing time and overcomes the current limitations of the conventional precipitation techniques in terms of large waste streams, product purity, and process scale-up.     

Compaction Properties of Composite Particles Consisting of Lactose with Sodium Alginate Prepared by Spray-Drying

Purpose. Composite particles of lactose with a small amount of sodium alginate were prepared by spray-drying (SD) in an effort to improve the compactibility of the polymer for direct compression. The compaction behavior of the SD composite particles with a range of polymer contents was investigated. Methods. Composite particles were prepared by spray-drying an aqueous solution of lactose and sodium alginate at various formulating ratios. Improvement in the compactibility of the composite particles was evaluated by measuring the tablet tensile strength, porosity-applied pressure profiles, stress relaxation, elastic recovery of the compressed powder, and surface properties of the tablets by scanning electron microscopy. Results. The tensile strength of compacts formed from the SD composite particles containing sodium alginate (10 wt%) was as high as that of spray-dried amorphous lactose. The improved compaction was attributed to the higher relaxation pressure and lower elastic recovery of the composite particles compared with -lactose monohydrate. However, increasing the sodium alginate content of the SD composite particles above 10 wt% led to a marked reduction in the tensile strength of the resultant tablets. Scanning electron micrographs revealed that composite particles with a good compactibility fused totally in the tablets while composite particles containing 15% or more sodium alginate retained their shape, even after compression. The presence of sodium alginate layered uniformly on the surface of the particles and the increase in the glass transition temperature of the particles, possibly due to interpolation of sodium alginate are responsible for the reduction in the fusion property of the composite particles on compression. Conclusions. Although increasing the sodium alginate content of SD composite particles led to an increase in their plastic deformation, fusion on compression was prevented by the presence of sodium alginate. The reduced compactibility of SD composite particles with an excess amount of sodium alginate was attributed to reduced cohesion and fusion of the particles during compression.     

超临界流体萃取肉桂挥发油工艺研究

目的：探讨肉桂挥发油的最佳提取工艺。方法：采用超临界CO2萃取技术提取挥发油。结果：最佳工艺条件为：萃取温度45℃、萃取压力45MPa、萃取时间2．5h、CO2流量20kg·h^-1。结论：优选的提取工艺条件稳定、可行。     

Temperature- and Moisture-Induced Crystallization of Amorphous Lactose in Composite Particles with Sodium Alginate Prepared by Spray-Drying

The purpose of this study was to investigate the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles prepared by spray-drying an aqueous solution of crystalline lactose and sodium alginate. The temperature-induced crystallization of amorphous lactose in the composite particles was suppressed by increasing the amount of sodium alginate in the particles. The stabilizing effect of sodium alginate on amorphous lactose in the composite particles was greater than that in physical mixtures having the same formulating ratios. The improved stability of amorphous lactose in the composite particles was attributed to an increase in the glass transition temperature (T_g) of the mixture. Moisture-induced crystallization of amorphous lactose was also retarded by increasing the amount of sodium alginate in composite particles. Although the T_g of the mixture was reduced by increasing the water content of the particles, the values were higher than that of 100% amorphous lactose when particles of the same water content were compared. The change in the T_g of the composite particles with increasing water content was interpreted as involving three components of the Gordon–Taylor equation. In the amorphous lactose–sodium alginate systems, the T_g values of the composite particles containing sodium alginate were higher than the theoretical line predicted by two components of the Gordon–Taylor equation. These results suggested that there was a specific interaction between the sodium alginate and lactose molecules. This specific interaction was suggested by the fact that only very little amorphous lactose was measured in the spray-dried composite particles stored under humid conditions using differential scanning calorimetry. This molecular interaction may also be partly responsible for the suppression of both the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles.     

超临界流体萃取技术及其在生物样本萃取中的应用

对超临界流体的性质、超临界流体萃取技术的特点及其在生物样本萃取中应用实例进行了介绍。超临界流体萃取技术是新近发展迅速并在生物样本萃取中具有独特优势的一门技术。     

Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique

Pharmaceutical Research - The emulsifiers in an exceedingly higher level are used in the preparation of drug loaded polymeric nanoparticles prepared by emulsification solvent evaporation method....     

超临界流体色谱法分离手性药物

综述了超临界流体色谱在手性药物分离方面的研究和应用，介绍了超临界流体色谱手性分离的分离方式、色谱装置及操作条件。超临界流体色谱是一种很有潜力的色谱分离技术，具有高效、快速等特点，可以有效地弥补高效液相色谱和气相色谱在手性药物分离方面的不足。     

超临界CO2流体技术制备纳豆激酶肠溶微丸的初探

以异丁烯酸-丙烯酸乙酯共聚物Eudragit L100-55为包衣材料,利用超临界CO2流体技术制备纳豆激酶口服肠溶包衣微丸,考察包衣效果,为纳豆激酶口服制剂的研究和开发提供实验依据.采用正交表考察各种因素对试验结果的影响;并按药典规定考察微丸在不同pH释放介质中的药物活性及释放行为.结果显示最适反应条件为:包衣材料和载药微丸质量比为1:2,反应压力和温度分别为20 MPa、35℃,增塑剂柠檬酸三乙酯及助溶剂乙醇均为10%(V/m),抗粘剂滑石粉虽对包衣反应稍有影响.但能显著改善微丸粘连问题.体外实验结果表明所制备的最佳状态肠溶微丸在人工胃酸(pH1.2)环境中2 h仅释放9.7%,并能保持近90%的活性状态;在pH6.8的模拟肠液释放介质中2 h内快速释放达75%.以超临界CO2流体技术制备的纳豆激酶口服肠溶包衣微丸,在人工胃酸环境中几乎不释药,可避免胃酸环境对纳豆激酶活性的破坏;在pH6.8的类肠液环境中药物释放快速而完全,有利于纳豆激酶在肠道中的吸收.     

Purification of Pharmaceutical Excipients with Supercritical Fluid Extraction

Supercritical fluid extraction (SFE), with carbon dioxide as the solvent, was tested for its ability to remove common reactive impurities from several pharmaceutical excipient powders including starch, microcrystalline cellulose (MCC), hydroxypropylcellulose (HPC), polyethylene oxide (PEO), and polyvinylpyrrolidone (PVP). Extraction of the small molecule impurities, formic acid and formaldehyde, was conducted using SFE methods under conditions that did not result in visible physical changes to polymeric excipient powders. It could be shown that spiked, largely surface-bound, impurities could be removed effectively; however, SFE could only remove embedded impurities in the excipient particles after significant exposure times due to slow diffusion of the impurities to the particle surfaces. Attempts at hydrogen peroxide extraction were hindered by its low solubility in CO₂, thereby effectively precluding SFE for removal of hydrogen peroxide from excipients. This work suggests that SFE will only be commercially useful for removal of low molecular weight impurities in polymeric excipients when migration of the impurities to the particle surfaces is sufficiently rapid for extraction to be completed in a reasonable time frame.     

复合中心对称设计法制备喜树碱非离子表面活性剂囊泡

采用复合中心对称设计法优化喜树碱非离子表面活性剂囊泡的处方和工艺，得到的优化条件为：药物与非离子表面活性剂用量比1：10，非离子表面活性剂与胆固醇用量比1：0．6，水合搅拌速度800r／min，水合温度55℃，50mg药物的分散介质体积50ml。