Recrystallization of sulfathiazole and chlorpropamide using the supercritical fluid antisolvent process

The supercritical antisolvent (SAS) process was used to modify the solid–state properties of sulfathiazole and chlorpropamide. Acetone, methanol, and ethyl acetate were employed as solvents for the pharmaceutical compounds, and carbon dioxide was used as an antisolvent. The effects of process parameters on the precipitate crystals such as carbon dioxide injection rate, type of solvent, and temperature were investigated. The SAS processed crystals show more ordered appearances with clean surfaces and sharp angles compared with the unprocessed particles. The crystal habit changed from tabular to acicular when the carbon dioxide injection rate increased. The X-ray diffraction patterns of the two compounds revealed variations of crystallinity and crystal orientations depending upon the injection rate, where the degree of crystallinity was found to be inversely proportional to the rate of injection. The analysis of differential scanning calorimetry indicated that both the injection rate and temperature influence the crystal's thermal stability which is related to the solid–solid transition and fusion. The crystal size significantly increased when the nucleation and crystal growth took place at a slow rate.     

Crystallization of sulfamethizole using the supercritical and liquid antisolvent processes

Sulfamethizole was crystallized using both the supercritical and liquid antisolvent processes. Acetone and N,N-dimethyl formamide (DMF) were selected as solvents for the pharmaceutical compound, and carbon dioxide and distilled water were used as antisolvents. In the supercritical antisolvent process, the effects of experimental conditions such as carbon dioxide injection rate, type of solvent, and temperature were investigated. In the liquid antisolvent process, the effect of ultrasound on the properties of crystal was examined. The various crystal habits such as tabular, platy, acicular, and prismatic were observed depending on the process and experimental conditions. Differential scanning calorimetry (DSC) measurement revealed that the carbon dioxide injection rate affected the crystallinity of sulfamethizole particles. Larger crystals were obtained at higher temperatures in the two antisolvent processes. The particle size distribution was mostly affected by the antisolvent injection rate and the application of ultrasound.     

非均质多孔盐水层中超临界CO_2的注入压力与饱和度分布特性

为了研究盐水层孔隙结构特性对CO2注入过程的影响,采用对数正态分布的随机分布孔隙率表征地下盐水层的非均质孔隙特性,引入与盐水层中局部温度和局部压力相适应的CO2密度和黏度,建立了超临界CO2-盐水体系的两相流驱替过程数学模型。通过数值模拟研究了超临界CO2注入的过程参数和盐水层特性对CO2注入特性和盐水层中饱和度分布的影响。研究表明:CO2的注入压力主要与盐水层的深度和盐水层的体积平均孔隙率有关,而受盐水层孔隙率分布的影响较小;盐水层的孔隙率分布特性对CO2饱和度分布影响非常显著;在盐水层总容积相同的条件下,深层盐水层的CO2存储容量比浅层盐水层的小,且注入压力大;在CO2封存过程中,应选择合适的注入速率,最大限度地提高盐水层封存容量的利用率。本文的计算方法和分析结果为超临界CO2的地下封存过程和注入后的评估方法等提供了计算方法和理论依据。     

超声催化超临界流体重结晶研究

探讨了超临界流体二氧化碳及其改性流体作为经典重结晶的溶剂及重结晶分离同分异构体菲蒽的加速结晶的不同条件，确证了超声振动能提高改性超临界二氧化碳重结晶过程的速率。     

Recrystallization of erlotinib hydrochloride and fulvestrant using supercritical antisolvent process

Recrystallization of two anti-cancer active pharmaceutical ingredients (APIs), erlotinib hydrochloride (erlotinib HCl) and fulvestrant, using supercritical antisolvent (SAS) process was investigated in this study. The most commonly used supercritical carbon dioxide was employed as the antisolvent. Effect of three process parameters including the operating temperature, pressure and solution flow rate have been studied. Analyses of the recrystallized erlotinib HCl and fulvestrant were examined by SEM, XRD and DSC. Erlotinib HCl was recrystallized from its mean particle size of 20 μm to 2 μm with different crystal habits. Different polymorphs of erlotinib HCl were obtained and confirmed from the XRD and DSC results. The prior art polymorph form A of erlotinib HCl showed enhanced dissolution rate by 3.6 times to its original polymorph form B. Significant particle size reduction was also obtained for fulvestrant. The mean particle size was reduced from its original value of 22 μm to 2 μm with much narrower particle size distribution. The cross-interaction effect between the operating temperature and pressure observed in the SAS treatment of fulvestrant was verified by the method of calculated mixture critical point (MCP). The micronized fulvestrant particles showed consistent polymorph as the original API, but with different crystal habits. It is confirmed that the SAS method is applicable for controlling the crystal properties of two APIs, erlotinib HCl and fulvestrant, which require rigorous control of physical characteristics.     

Preparation of poly(L-lactic acid) submicron particles in aerosol solvent extraction system using supercritical carbon dioxide

The aerosol solvent extraction system process (ASES), which is one of the supercritical anti solvent processes (SAS), was used to produce poly(L-lactic acid) (PLLA) into the submicron particles. Dichloromethane (DCM, CH₂Cl₂) and carbon dioxide were selected as a solvent and as an antisolvent for PLLA, respectively. The objective of this study was to investigate the effect of the various process parameters such as temperature, pressure, and solution concentration on PLLA particles. With increasing temperature and pressure, particle size was increased. Also, higher PLLA concentration led to larger particle size and broader particle size distribution. A scanning electron microscope (SEM) was used to observe the morphology and size of PLLA particles recrystallized by ASES process. The mean particle size and its distribution of processed particles were measured by using a laser diffraction particle size analyzer (PSA).     

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.     

超临界CO2萃取回收SBA-15中的有机模板剂

在200 mL高压萃取釜内,对含夹带剂的超临界CO2萃取回收SBA-15中有机模板剂P123(EO20PO70EO20)的最佳工艺条件进行了研究,考察了夹带剂种类、萃取温度、萃取压力、夹带剂流量对回收率的影响,确定最佳萃取工艺条件为：甲醇作夹带剂,温度45℃,压力27 MPa,夹带剂流量4 mL/min,萃取时间1.5 h,在此条件下P123回收率可达73.7%. 对不同方法脱除P123后的SBA-15进行了表征,结果表明,含甲醇夹带剂的超临界CO2萃取法是一种高效环保的方法,且得到的SBA-15保留了很好的骨架有序性,不会造成骨架硅羟基脱除,克服了高温焙烧脱除模板剂造成的孔道收缩问题.     

Micronization of Three Active Pharmaceutical Ingredients Using the Rapid Expansion of Supercritical Solution Technology

The rapid expansion of supercritical solution (RESS) technology was applied to recrystallize and micronize three active pharmaceutical ingredients (APIs) of monobenzone, ethylparaben, and kojic acid. All unprocessed (original) APIs had a large mean particle size over 200 μm with wide particle size distribution. Supercritical carbon dioxide served as the solvent to extract each API in a high-pressure vessel. The nearly saturated supercritical solution was then expanded through a capillary spray nozzle to ambient pressure state. The APIs were recrystallized in a very short time period. The final API particles with submicron sizes were obtained with much less intensity of crystallinity. The optimal RESS process parameters and the improved result of the in vitro dissolution test for the API of ethylparaben are reported.     

Separation of m-Xylene and Ethylbenzene in Gaseous Carbon Dioxide

Abstract

The separation of an equal amount of ethylbenzene (EB) and m-xylene on silicalite using carbon dioxide as the carrier was studied. The experimental results indicated that operations in gaseous carbon dioxide provide a better separation efficiency than those at supercritical conditions. The effects of temperature, pressure, and flow rate on separation were also examined. It was found that the most appropriate conditions for obtaining purities of EB and m-xylene over 98% were a temperature around 353 K, a pressure of 40.8 atm, and a flow rate about 15 cm³/min. Comparison of the response curves for single- and two-component injection systems indicated that the model proposed by Gu et al. might be employed to interpret the data.     

Correlation of solubility data of azo disperse dyes with the dye uptake of poly(ethylene terephthalate) fibres in supercritical carbon dioxide

Solubility data of disperse azo dyes in supercritical carbon dioxide are presented for dyeings of poly(ethylene terephthalate) fibres with CI Disperse Red 167:1, carried out at 200–300 bar and 80–120 °C, with varying amounts of adulterants. The same dyeings were also carried out in water for comparison. Scanning electron micrographs were taken of the dyes which show a growth of dye crystals during treatment in supercritical carbon dioxide. The paper reports that at 120 °C, melting of the pure dye CI Disperse Red 167:1 is observed. The presence of adulterants in the dye formulations help prevent agglomeration by acting as spacers between the dye molecules. Dyeings of PETP carried out under conditions of the highest solubility of the dye in supercritical carbon dioxide do not necessarily result in a very high dye uptake. This was shown by pressure- and temperature-dependent dyeing experiments of PETP in supercritical carbon dioxide.     

超临界CO_2萃取苕叶细辛挥发油

采用正交实验法对超临界CO2萃取苕叶细辛挥发油的条件进行了研究。考察了萃取温度、压力、CO2流量等因素在不同水平下对苕叶细辛挥发油提取率的影响。得到了超临界CO2萃取苕叶细辛挥发油的最佳实验条件:萃取压力20MPa,温度40℃,CO2流量35kg/h和萃取时间80min,得率为1 72%。水蒸气蒸馏提取得率为0 24%。超临界CO2萃取的收率高,萃取时间短。     

用石蜡-CO_2超临界流体快速膨胀在流化床中进行细颗粒包覆

对超临界流体快速膨胀技术在流化床中进行细颗粒的表面包覆进行了研究 ,以实现细颗粒中关键成分的有效控制释放 .实验研究了含有包覆剂———石蜡的超临界二氧化碳流体通过微细喷嘴快速膨胀到装有细颗粒的流化床中 ,膨胀射流中所产生的微核在细颗粒表面均匀沉积 ,形成细颗粒表面薄层包覆 .结果分析表明 ,超临界流体快速膨胀前的温度是包覆过程的关键参数 ,通过控制操作过程参数可以获得良好的包覆结果     

Preparation of aerogel beryllium borate with supercritical carbon dioxide drying

A supercritical carbon dioxide drying technique was developed to prepare nanometer particulate materials. The technique consists of preparation of an aqueous gel, filtering, washing, replacement of the water in the gel with a mixture solvent of n-butanol and ligroin and supercritical carbon dioxide drying. The product was characterized with TEM, XRD and X-ray small-angle scattering. The results indicated that an amorphous aerogel of the beryllium borate was obtained with this technique. The diameter of the product particles was about 7 nm. Isopropyl alcohol supercritical drying was also used to prepare aerogel beryllium borate, where recrystallization took place due to the high critical temperature of isopropanol.     

Relationship between the solubility of disperse dyes and the equilibrium dye adsorption in supercritical fluid dyeing

In order to understand the dyeing behaviour of synthetic fibres in supercritical carbon dioxide, the solubility of some disperse dyes in supercritical fluid, as well as the rate of dyeing and the equilibrium adsorption of these dyes, have been studied. Dye solubility was measured by a dynamic analytic method at a range of pressure (7.5–25 MPa) and temperature (50–145 °C). The apparent rate of dyeing was measured and the dyeing isotherm was obtained by plotting the equilibrium dye adsorption against the equilibrium dyebath concentration. Linear isotherms were obtained when poly(ethylene terephthalate) samples were dyed with the disperse dyes. The mechanism of dyeing using supercritical carbon dioxide was discussed by considering the solubility, the dyeing rate and the dyeing isotherm.     

超临界CO_2萃取β-胡萝卜素的实验研究

用超临界CO2技术对β 胡萝卜素进行了萃取试验,考察了CO2用量、萃取压力、温度等对浸膏得率的影响,从而得出了超临界CO2萃取β 胡萝卜素的最佳工艺条件。     

两步法制备牛蒡子苷元

对用超临界CO2从中药材牛蒡子中萃取牛蒡子苷元进行了优化研究。结果表明,压力、温度、CO2流量和提取时间对牛蒡子苷元萃取有较大影响,最佳工艺条件为:压力35 MPa,温度40℃,CO2流量6.0 L/h,提取时间50 min;在上述最佳工艺条件下,无需任何夹带剂,牛蒡子萃取物经简单脱脂处理,即可制得质量分数为99.66%的高纯度牛蒡子苷元,其提取率为0.45%。与传统溶剂柱层析提取方法相比,提取率提高了2.75倍,简单、安全、高效。     

α-细辛醚在超临界CO_2中溶解度测定

测定了α 细辛醚在超临界CO2 中的溶解度。考察了压力、温度等因素对α 细辛醚在超临界CO2 中溶解度的影响。结果表明α 细辛醚在超临界CO2 中的溶解度随着压力的增加而增大 ,随着温度的增加而减小 ,并符合经典的Chrastil表达式。     

Particle design using supercritical fluids: Literature and patent survey

As particle design is presently a major development of supercritical fluids applications, mainly in the pharmaceutical, nutraceutical, cosmetic and specialty chemistry industries, number of publications are issued and numerous patents filed every year. This document presents a survey (that cannot pretend to be exhaustive!) of published knowledge classified according to the different concepts currently used to manufacture particles, microspheres or microcapsules, liposomes or other dispersed materials (like microfibers):RESS: This acronym refers to ‘Rapid Expansion of Supercritical Solutions’; this process consists in solvating the product in the fluid and rapidly depressurizing this solution through an adequate nozzle, causing an extremely rapid nucleation of the product into a highly dispersed material. Known for long, this process is attractive due to the absence of organic solvent use; unfortunately, its application is restricted to products that present a reasonable solubility in supercritical carbon dioxide (low polarity compounds).GAS or SAS: These acronyms refer to ‘Gas (or Supercritical fluid) Anti-Solvent’, one specific implementation being SEDS (‘Solution Enhanced Dispersion by Supercritical Fluids’); this general concept consists in decreasing the solvent power of a polar liquid solvent in which the substrate is dissolved, by saturating it with carbon dioxide in supercritical conditions, causing the substrate precipitation or recrystallization. According to the solid morphology that is wished, various ways of implementation are available:GAS or SAS recrystallization: This process is mostly used for recrystallization of solid dissolved in a solvent with the aim of obtaining either small size particles or large crystals, depending on the growth rate controlled by the anti-solvent pressure variation rate;ASES: This name is rather used when micro- or nano-particles are expected; the process consists in pulverizing a solution of the substrate(s) in an organic solvent into a vessel swept by a supercritical fluid;SEDS: A specific implementation of ASES consists in co-pulverizing the substrate(s) solution and a stream of supercritical carbon dioxide through appropriate nozzles.PGSS: This acronym refers to ‘Particles from Gas-Saturated Solutions (or Suspensions)’: This process consists in dissolving a supercritical fluid into a liquid substrate, or a solution of the substrate(s) in a solvent, or a suspension of the substrate(s) in a solvent followed by a rapid depressurization of this mixture through a nozzle causing the formation of solid particles or liquid droplets according to the system.The use of supercritical fluids as chemical reaction media for material synthesis. Two processes are described: thermal decomposition in supercritical fluids and hydrothermal synthesis.We will successively detail the literature and patents for these four main process concepts, and related applications that have been claimed. Moreover, as we believe it is important to take into account the user's point-of-view, we will also present this survey in classifying the documents according three product objectives: particles (micro- or nano-) of a single component, microspheres and microcapsules of mixtures of active and carrier (or excipient) components, and particle coating.