超临界反溶剂过程制备银杏叶提取物超细微粒

超临界反溶剂过程是近年来提出的一种制备纳微米粉体材料的新方法。应用超临界反溶剂过程实验装置制备银杏提取物(GBE)超细微粒,实验中以乙醇为溶剂,超临界CO2为反溶剂,制备出平均直径在1μm至2μm范围内的GBE超细微粒。同时研究了操作压力、操作温度及二氧化碳与溶液流率比等操作参数对制备的超细微粒粒径、形态及粒径分布的影响。实验结果表明：操作压力、温度对制备的GBE微粒影响较为显著。     

超临界流体技术与超细颗粒的制备

本文对超临界流体技术在超细颗粒制备中的应用进行了综述，介绍了ＲＥＳＳ过程、ＧＡＳ过程和超临界流体反微乳技术的机理和装置。     

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。     

超临界反溶剂法制备超细微粒

对超临界反溶剂法制备超细微粒的工艺原理、实验装置及研究现状作了介绍,详细分析了该工艺在含能材料、药品及催化剂等领域的应用、工艺及研究成果.     

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     

超临界反溶剂过程传质数学模型

建立了有机溶剂(甲苯)液滴与超临界反溶剂(超临界CO2)之间的传质模型,用于模拟超临界反溶剂制备微纳米粉体材料的传质过程。该模型考虑了双向传质过程,既有反溶剂向溶液的扩散过程,又有溶液中的溶剂向反溶剂的“汽化”过程。液滴的传质行为是影响颗粒形态和尺寸分布的关键因素。假定传质是在一个孤立的微小液滴与包围着它的反溶剂连续相间进行的,利用描述液滴内和液滴外某一点行为的连续方程、扩散方程、能量方程和动量方程,及界面上的守恒条件进行耦合,从而建立传质过程的数学模型,并给出求解方程和求解的边界条件和初始条件,进行数值求解。     

异丙醇铝在超临界丙烷中的溶解度与粒子制备

选用丙烷作溶剂在不同条件下进行超临界溶液快速膨胀（Rapid Expansion of Su-percritical Solution-RESS）制备异丙醇铝超细粒子的实验研究。同时用流动法装置测定了温度为388.15K和403.15K、压力为（21.5～30.5）MPa条件下异丙醇铝在超临界丙烷中的溶解度,并对其进行了关联计算。     

反溶剂超声法制备超细磷酸二氢铵粉体

在溶剂(水)-反溶剂(乙醇)体系下,利用反溶剂超声分散法制备磷酸二氢铵超细粉体,探索得到一种简便、经济的超细粉体制备方法,为后续灭火材料的制备提供基础。研究了超声时间、溶液初始浓度、溶剂-反溶剂体积比、超声功率等条件对磷酸二氢铵粉体形貌和粒径的影响。利用纳米激光粒度仪、扫描电镜、红外光谱、X-射线衍射等对原料和产物进行表征分析。实验结果表明:超声时间为4 min,磷酸二氢铵溶液浓度为0.1 mol/L,溶剂反溶剂体积比为2∶8,超声功率为仪器总功率的9%时,可得粒径500 nm左右的磷酸二氢铵纳米流体;高速离心及真空干燥后,得到粒径2~3μm的固体颗粒产物。     

K2CO3生产中NH4Cl废水的回收技术

分析了反渗透的基本原理，详细介绍了采用反渗透膜分离技术回收利用K2CO3生产过程中产生的含NH4Cl废水的工艺过程。处理低浓度含NH4Cl废水100m^3／h和高浓度含NH4Cl废水40m^3／h工业化装置建成投产后，处理前低浓度废水含NH4Cl1000mg／L，高浓度废水含NH4Cl10000mg／L，pH=8～10；处理后，产品淡水含NH4Cl≤10mg／L、pH=7～8，产品浓水含NH4Cl≥60000mg／L、pH=8～lO。该装置的投运，取得了明显的经济效益和社会效益。     

碳酸氢铵法制氟化铝的研究

碳酸氢铵与氟硅酸反应生成NH4F溶液和SiO2 沉淀。NH4F溶液与硫酸铝反应得 (NH4) 2 SO4溶液和 β-AlF3 ·3H2 O晶体。经分离和加工后 ,可分别制得氟化铝产品和副产品硫酸铵、白炭黑。论述了制备原理和工艺流程 ,研究了影响产品质量和收率的因素。     

Interactions of phase equilibria,jet fluid dynamics and mass transfer during supercritical antisolvent micronization

Supercritical antisolvent (SAS) precipitation has been successfully used in the micronization of several compounds. Nevertheless, the role of high-pressure vapor–liquid equilibria, jet fluid dynamics and mass transfer in determining particle size and morphology is still debated. In this work, CO₂ has been adopted as supercritical antisolvent and elastic light has been used to acquire information on jet fluid dynamics using thin wall injectors for the investigation of the liquid solvents acetone and DMSO at operating conditions of 40 °C in the pressure range between 6 and 16 MPa. The results show that two-phase mixing after jet break-up is the phenomenon that characterizes the jet fluid dynamics at subcritical conditions. When SAS is performed at supercritical conditions a transition between multi-phase and single-phase mixing is observed by increasing the operating pressure. Single-phase mixing is due to the very fast disappearance of the interfacial tension between the liquid solvent and the fluid phase in the precipitator. The transition between these two phenomena depends on the operating pressure, but also on the viscosity and the surface tension of the solvent. Indeed, single-phase mixing has been observed for acetone very near the mixture critical point, whereas DMSO showed a progressive transition for pressures of about 12 MPa.In the second part of the work, a solute was added to DMSO to study the morphology of the microparticles formed during SAS precipitation at the different process conditions, to find a correlation between particle morphology and the observed jet. Expanded microparticles were obtained working at subcritical conditions; whereas spherical microparticles were obtained operating at supercritical conditions up to the pressure where the transition between multi- and single-phase mixing was observed. Nanoparticles were obtained operating far above the mixture critical pressure. The observed particle morphologies have been explained considering the interplay among high-pressure phase equilibria, fluid dynamics and mass transfer during the precipitation process.     

Screening design of experiment applied to supercritical antisolvent precipitation of amoxicillin: Exploring new miscible conditions

Microparticles of amoxicillin (AMC) have been precipitated by supercritical antisolvent process (SAS) using carbon dioxide and N-methylpyrrolidone (NMP) as antisolvent and solvent, respectively. A fractional factorial design of experiment (DOE) with 2⁷⁻⁴ experiments has been used. Mean particle size (PS) and particle size distribution (PSD) of the processed amoxicillin have been chosen as responses to evaluate the process performance. In a previous work, a DOE was applied too, but now, the range of operating conditions investigated has been changed to let the process take place in a single supercritical phase. Within this range, concentration is again the key factor having most effect on both PS and PSD and thus, the most important factor for controlling the formation of sub-microparticles of amoxicillin by the SAS technique. Moreover, all the experiments included in the new design matrix led to a successful precipitation of amoxicillin.     

Micronization of taxifolin by supercritical antisolvent process and evaluation of radical scavenging activity

The aim of this study was to prepare micronized taxifolin powder using the supercritical antisolvent precipitation process to improve the dissolution rate of taxifolin. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters, such as temperature (35-65 °C), pressure (10-25 MPa), solution flow rate (3-6 mL/min) and concentration of the liquid solution (5-20 mg/mL) on the precipitate crystals were investigated. With a lower temperature, a stronger pressure and a lower concentration of the liquid solution, the size of crystals decreased. The precipitation temperature, pressure and concentration of taxifolin solution had a significant effect. However, the solution flow rate had a negligible effect. It was concluded that the physicochemical properties and dissolution rate of crystalline taxifolin could be improved by physical modification such as particle size reduction using the supercritical antisolvent (SAS) process. Further, the SAS process was a powerful methodology for improving the physicochemical properties and radical scavenging activity of taxifolin.     

Role of hydrodynamics in supercritical antisolvent processes

An experimental study of hydrodynamics role in the supercritical antisolvent (SAS) process is here presented. Jet dispersion and atomization of a liquid phase into a dense one have been characterized for miscible systems and for commonly used conditions in SAS processes. The critical atomization jet velocity tends to the same value for all the systems studied. The dispersion has also been studied in the case of an organic solution containing the solute to be precipitated. The presence of sulfathiazole in a concentration up to 10 wt% does not influence the liquid jet dispersion. The nucleation zone has been located: crystals are not formed in the plain jet but in the entities resulting from the jet break-up. The observation of the crystals formed shows that the key-point is the mixing state more than the atomization state to form fine particles. However, atomization conditions lead to more homogeneous powder characteristics.     

Preparation of bitter taste masked cetirizine dihydrochloride/β-cyclodextrin inclusion complex by supercritical antisolvent (SAS) process

Rapid-disintegrating tablets (RDT) provide many advantages, such as rapid onset of action and assisting those patients who have difficulty swallowing. An important consideration in the formulation of RDT is masking the bitter taste of the drug to ensure patient compliance. The purpose of this study was to evaluate the possibility of inclusion complexation as a means of formulating taste masked cetirizine dihydrochloride (CTZ) rapid-disintegrating tablets. The inclusion complex between CTZ and β-cyclodextrin (β-CD) was prepared using a supercritical antisolvent (SAS) process, where dimethylsulfoxide (DMSO) was used as a liquid solvent and carbon dioxide (CO₂) as a supercritical antisolvent.Compared to large, irregular shaped products of freeze-drying method, small, spherically shaped, uniformly sized CTZ/β-CD inclusion complex products were successfully prepared by the SAS process. Concerning the structure of the complex, space conformation of the phenyl ring and chlorophenyl ring of CTZ in the β-CD hydrophobic cavity was confirmed by nuclear magnetic resonance spectroscopy (¹H NMR) and two-dimensional rotating frame overhauser effect spectroscopy (2D ROESY) studies. The obtained inclusion complex products prepared by both freeze-drying method and SAS process have the same efficacy in regards to dissolution characteristics and show the effective taste masking as compared to pure CTZ and CTZ/β-CD physical mixtures. In addition, the resulting products prepared by SAS process have negligible amount of residual solvent.     

Supercritical antisolvent precipitation of andrographolide from Andrographis paniculata extracts: Effect of pressure, temperature and CO2 flow rate

Andrographis paniculata extracts were precipitated using the so-called supercritical antisolvent (SAS) technique. Ethanol was used as the solvent and compressed CO₂ as the antisolvent. The effects of process operating conditions (pressure: 5-24 MPa, temperature: 308-328 K and CO₂ flow rate: 0.5-1.5 g/min) on particle size and morphology of precipitated andrographolide were evaluated. X-ray diffraction (XRD) patterns showed significant changes in andrographolide morphology depending on process operating conditions; both column-like and slice-like crystals were observed depending on operating conditions. Crystals with mean diameters of 3.30-228.35 μm were produced, smaller crystals were obtained at high pressure, low temperature and high CO₂ flow rate and vice versa for large crystals. In addition, SAS process also produced high precipitation yields, since solubility of andrographolide is small in the supercritical CO₂ plus ethanol. When operating under subcritical conditions, amorphous particles were produced.     

Solvent effect on particle morphology in recrystallization of HMX (cyclotetramethylenetetranitramine) using supercritical carbon dioxide as antisolvent

Supercritical fluid processes have gained great attention as a new and environmentally benign method of preparing the microparticles of energetic materials like explosives and propellants. In this work, HMX (cyclotetramethylenetetranitramine) was selected as a target explosive. The microparticle formation of HMX using supercritical antisolvent (SAS) recrystallization process was performed and the effect of organic solvent on the size and morphology of prepared particles was observed. The organic solvents used in this work were dimethylsulfoxide (DMSO), N,N-dimethylformamide (DMF), cyclohexanone, acetone, and N-methyl pyrrolidone (NMP).     

Co-precipitation of amoxicillin and ethyl cellulose microparticles by supercritical antisolvent process

Microparticles of ethyl cellulose (EC) and amoxicillin (AMC) have been precipitated by a supercritical antisolvent process (SAS) using CO₂ as the antisolvent and a mixture of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) as solvents. Combinations of three temperatures (308, 323 and 333 K) and four pressures (100, 150, 200 and 250 bar) were assessed in the vessel and the rest of the variables were held constant (i.e. CO₂ flow rate, sample flow rate, washing time, nozzle diameter and the amoxicillin:ethyl cellulose ratio). Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and elemental analysis (EA) were used to determine the particle size and shape and to confirm the presence of both compounds in the resulting precipitates. In most cases, mixed amoxicillin and ethyl cellulose particles were produced with sizes in the micrometer range. Pressure and temperature effects on the co-precipitation were investigated. The release behaviour of the microparticles precipitated by the SAS process was evaluated in two biological fluids – simulated gastric and simulated intestinal fluids. Co-precipitated materials allowed a slower drug release rate than pure drug.     

Preparation and characterization of camptothecin powder micronized by a supercritical antisolvent (SAS) process

Micronized camptothecin (CPT) is prepared with a supercritical antisolvent (SAS) apparatus using dimethyl sulfoxide (DMSO) as solvent and carbon dioxide as antisolvent. Four factors, namely CPT solution concentration and flow rate, precipitation temperature and pressure are optimized by a four-level orthogonal array design (OAD). By analysis of variance (ANOVA), only precipitation pressure has a significant effect on the MPS of micronized CPT. The optimum micronization conditions are determined as follows: CPT solution concentration 1.25 mg/ml, CPT solution flow rate 6.6 ml/min, precipitation temperature 35 °C and precipitation pressure 20 MPa. Under the optimum conditions, micronized CPT with a MPS of 0.25 ± 0.020 μm is obtained. The micronized CPT obtained was characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscope (AFM), High performance liquid chromatography-mass spectrometry (LC-MS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Differential scanning calorimeters (DSC) and Gas chromatography (GC) analyses. The results showed that the obtained CPT particles have lower crystallinity and SAS micronization process does not induce degradation of CPT. In addition, the residual DMSO is less than the ICH limit for class 3 solvents.