Amoxicillin and Ethyl Cellulose Precipitation by Two Supercritical Antisolvent Processes

Composites of amoxicillin and ethyl cellulose in the micrometer range were precipitated by supercritical antisolvent (SAS) processes using carbon dioxide as antisolvent and a mixture of dichloromethane and dimethylsulfoxide as solvents. Morphologies and mean diameter ranges were analyzed by scanning electron microscopy. X‐ray photoelectron spectroscopy (XPS) and high‐performance liquid chromatography were carried out in order to ensure successful coprecipitation and to determine the amoxicillin contents in the final products. The SAS processes used differ mainly in the way in which the solutions are introduced: through a normal or a coaxial nozzle. The XPS results provided proof that amoxicillin was not distributed in the same way in all the samples. The release behavior of the composites obtained was evaluated in two biological fluids, i.e., simulated gastric and simulated intestinal fluids. The different systems led to the release of the drug in different ways; but in all cases slower solubilization was obtained than for the pure drug.     

Precipitation and Characterization of Chelerythrine Microparticles by the Supercritical Antisolvent Process

Chelerythrine was successfully micronized from methanol solution using Supercritical Carbon Dioxide (SC‐CO₂) as an antisolvent via the Solution Enhanced Dispersion by Supercritical Fluids through the Prefilming Atomization (SEDS‐PA) process. The morphology and particle size of the chelerythrine microparticles were visually analyzed by scanning electron microscopy (SEM). For the purpose of the optimizing operating conditions of the SEDS‐PA process, the influences of the experimental variables, i.e., temperature, pressure, solution flow rate and initial solution concentration, on the particle size and morphology of chelerythrine microparticles are discussed in detail. The results show that the best process conditions for the micronization of chelerythrine are: T = 313 K, P = 20 MPa, C = 2.0 g/L and F = 2.0 mL/min. The precipitates obtained under the optimized experimental conditions are short rod‐like chelerythrine microparticles with a mean particle size of 0.1–1 μm in width.     

Recrystallization of Salicylamide using a Batch Supercritical Antisolvent Process

Recrystallization of the nonsteroidal anti‐inflammatory drug salicylamide was investigated using a batch supercritical antisolvent (SAS) precipitation process. Carbon dioxide was used as the antisolvent, and acetone, ethanol and ethyl acetate were used as solvents. Particle morphology determined by SEM showed that particles with a regular shape were obtained from the SAS process. The crystal structure analyzed by XRD showed that the intensities of specific peaks were modified. No decomposition or deterioration was confirmed by DSC measurements where the melting temperature remained the same after SAS recrystallization. The effects of process parameters were investigated with acetone as the solvent. At a higher pressure of 110 bar, a higher saturation concentration of 90 %, and a lower temperature of 293 K, the length of the rectangular particles decreased to 50 μm. This showed a significant change from the irregular and broken particle shapes with particle sizes up to 200 μm before processing by SAS.     

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     

New Insights into Acrylic Polymer Precipitation by Supercritical Fluids

Nanosystems based on polymers have attracted much attention due to the almost infinite diversity. In the past decades, the application of supercritical fluids for polymeric particle precipitation has been developed as an alternative to conventional processes. Here, precipitation of an acrylic copolymer was attempted by the rapid expansion of supercritical solutions (RESS) and successful by supercritical antisolvent (SAS) processes. In addition, the nanoparticles were characterized with different techniques. The polymer concentration, pressure, temperature, liquid solution flow rate and nozzle diameter effects were also evaluated with regard to particle size and the particle size distribution of this polymer.     

超临界CO2GAS沉析HMX制细过程的影响因素

研究了超临界CO2GAS沉析丙酮溶液中HMX的过程压力、温度、溶液初始浓度和溶液的膨胀速度及影响晶体粒度的因素。结果表明，压力增加，沉析颗粒的平均粒度减小；温度控制沉析晶体的晶型，对颗粒度的影响相对较小，温度增加，沉析平均粒度略有增加；溶液初始浓度对平均粒度的影响相对较大，膨胀速度亦是影响粒度及其分布的一个因素。快速膨胀溶液．并使过饱和度足够大，使过饱和度主要消耗在成核上，可得到颗粒小、分布窄的HMX颗粒。     

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。     

Supercritical Fluids in Catalysis: Opportunities of In Situ Spectroscopic Studies and Monitoring Phase Behavior

A number of homogeneous and heterogeneous catalytic reactions have been successfully performed in supercritical fluids (SCFs). An overview on recent developments in the areas of alkylation, isomerization, hydrogenation, partial oxidation, amination, and CO₂-fixation using heterogeneous catalysts and supercritical fluids is given. Additionally, strategies towards a more fundamental understanding of catalytic reactions in supercritical fluids are outlined. One aspect is the identification of phase behavior in such multicomponent systems. Their complexity and the input of in situ monitoring is discussed. It is proposed that binary fluid mixtures are an ideal guide for simplifying and understanding the phase behavior in reaction mixtures. In order to strengthen the future use of this knowledge, e.g., for optimization of reactions in SCFs, an overview on the different topologies of binary mixtures is given. Another aspect is in situ characterization of the catalytic reaction and their intermediates, the intermolecular interactions in the fluid, the heterogeneous catalyst phase, and the solid/fluid interphase. The opportunities of various available spectroscopic tools, applicable in situ, are also reviewed by referring to examples from homogeneous catalysis or low-pressure studies.     

聚乙二醇SAS微粒化的研究

经SAS微粒化实验研究,确定了聚乙二醇SAS沉析操作的优化条件:温度为25℃、压力为8MPa,反萃取剂CO2的密度为0.778gL-1,聚乙二醇/丙酮溶液的浓度为5~15 gL-1,溶液流量为1~5mLmin-1,过程为连续操作。实验所得聚乙二醇微粒的平均尺寸小于0.1mm,而其尺寸分布为0.033~0.38mm。     

Heterogeneous Catalysis in Supercritical Media,Part 3: Other Media

For technical applications, those reactions in supercritical fluids are of particular interest which have significant advantages over conventional methods or which are impossible in classical solvents or in the gas phase. This last part of the trilogy deals with heterogeneously catalyzed reactions in supercritical fluids other than carbon dioxide or water.     

Particle formation in supercritical fluids—Scale-up problem

The process of antisolvent precipitation of particles, termed solution enhanced dispersion by supercritical fluids (SEDS™), is applied to precipitate the model drug, paracetamol, from ethanol solutions. In the SEDS process the substrate solution is quickly mixed in a mixing chamber of the coaxial two-component nozzle with an antisolvent, represented in this case by the supercritical CO₂. Resulting partially mixed, highly supersaturated solution is introduced into the precipitation vessel as a jet, which generates intensive circulation of residual fluids that dilute the fresh supersaturated solution. Nucleation starts in the nozzle chamber, whereas particle growth completes the process in the precipitation vessel. The process is carried out above the mixture critical pressure; the antisolvent is thus completely miscible with the solvent. Under such conditions the macro-, meso-, and micro-mixing processes can affect the particle size distribution (PSD) and should be considered when the process is scaled up. Scaling up considerations of the precipitation process are based on scale-up rules, CFD simulations and experimental data for paracetamol precipitation. In simulations the model presented earlier (Ba?dyga et al., 2004) that is based on the population balance equation and CFD modelling of compressible flow processes is applied. Results of experimental investigations and numerical simulations are applied to verify scale-up strategies for the SEDS processes.     

In situ quantification of minor compounds in pressurized carbon dioxide using Raman spectroscopy

In this work, we present an optical approach that allows quantification of compounds dissolved down to a sub 10 ppm (molar) level in supercritical carbon dioxide (scCO₂) by in situ Raman spectroscopy. The quantification strategy is based on the consideration of Raman signal intensity ratios and of weak Raman signals of CO₂. The first measure makes the quantification strategy independent of the refractive index, laser power fluctuations and changes in alignment, and is thus robust against variations of the operation conditions. The second measure circumvents the classical challenges related to the dynamic range limit of detectors, which is inherent to the quantification of minor compounds. Example solubilities of the wax alkyl ketene dimer (AKD) in CO₂ were quantified at 333 K and a range of pressures from 10 MPa to 18 MPa. The solubilities are between 0.1 mg g⁻¹ and 1.5 mg g⁻¹ corresponding to ∼9 ppm and ∼132 ppm (molar), respectively.     

Effects of Fine Scale Turbulent Flow and Mixing in Agglomerative Precipitation

Precipitation of a solid product from aqueous ionic solutions, including mixing, fast chemical reaction, nucleation, growth and agglomeration of crystals is considered. This work concentrates on the phenomenon of particle agglomeration which dominates the precipitation process at high supersaturation. Modeling of particle collision includes effects of bulk fluid motion, Brownian diffusion and colloidal forces for particles of equal and unequal size. The concept of probability of agglomeration based on multifractal formalism is introduced and applied. A simplified version of the model is linked to CFD and results of computations are compared with experimental data for barium sulfate precipitation.     

超临界流体萃取的溶媒和挟带剂

本文介绍了超临界萃取的原理，溶媒及挟带剂。