A comparative study of supercritical fluid extraction and accelerated solvent extraction of lipophilic compounds from lignocellulosic biomass

The Box-Behnken experimental design technique investigated a comparative study of supercritical fluid extraction (SFE) and accelerated solvent extraction (ASE) of lipophilic compounds from pinewood sawdust. A response surface methodology was used to examine the effect of independent parameters and optimize the extraction yield of lipophilic compounds. The results showed that the increase in extraction temperature used for ASE positively influenced the yield of lipophilic compounds, whereas an increase in the flow rate of the cosolvent at temperature 50 °C, and pressure of 300 bar increased the yield achieved by SFE. The experimental data's quadratic polynomial models gave a coefficient of determination (R²) of 0.87 and 0.80 for ASE and SFE, respectively. The optimum conditions of ASE were temperature (160 °C), static time (12.5 mins), and static cycle (1), which resulted in a maximum yield of 4.2%. The optimum SFE conditions were temperature (50 °C), pressure (300 bar), carbon dioxide (CO₂) flow rate (3.2 ml/min), and a 2 ml/min cosolvent flow rate that yielded 2.5% lipophilic compounds. ASE yielded higher extraction efficiency than SFE. Fourier transform infra-red (FTIR) spectroscopy and thermal analyses TGA/DSC evaluated the ultimate analyses of the lipophilic extracts. The FTIR results confirmed the presence of aliphatic groups, hydroxyl groups, and carboxyl groups. The thermal analysis showed that the degradation temperature of the lipophilic compounds occurred between 250 and 450 °C. Thereafter, Pyrolysis-Gas Chromatography Mass Spectrometry (Py-GC/MS) was used to identify the lipophilic compounds, which showed that the extracts were rich in fatty acids and terpenes.     

Physical and Chemical Stability of Miconazole Liposomes Prepared by Supercritical Aerosol Solvent Extraction System (ASES) Process

The aerosol solvent extraction system (ASES) process was applied to prepare miconazole (MCZ) liposomes in a dry and reconstitutable form, the optimized temperature and pressure of which were 35°C and 8.0 MPa, respectively. The influence of compositions of phosphatidylcholine (PC), cholesterol (CHOL), and poloxamer 407 (POLOX) as well as the pH of hydration medium on physical and chemical stability of both dry microparticles and liposomes hydrated from them were examined following storage at 4°C and 25°C for 3 months. MCZ microparticles in dry powder were stable on storage at 4°C but degraded considerably after storage at 25°C. MCZ liposomes hydrated from dry ASES-prepared microparticles at pH 4.0 tended to aggregate, whereas those hydrated at pH 7.2 tended to reduce in size on storage, especially with the addition of CHOL. Liposomes with high MCZ content stored at 4°C degraded faster than when stored at 25°C. Addition of POLOX tended to retard the degradation of MCZ liposomes, whereas CHOL appeared to enhance the degradation on storage under both conditions. The chemical degradation of MCZ liposomes appeared to follow the acid-catalyzed hydrolysis. The MCZ liposomes prepared by the ASES process in this study were substantially internalized after being incubated with human lymphocytes.     

超临界CO_2萃取木香顺气丸中木香和砂仁的工艺研究

目的优选木香顺气丸中木香和砂仁的超临界CO2萃取工艺。方法采用单因素及正交试验的方法,考察萃取压力、温度、时间、药材粒度对萃取率的影响。结果优选的萃取工艺为:木香、砂仁粉碎成粗粉,萃取压力30 MPa,温度40℃,萃取3 h。结论使用超临界CO2萃取工艺,操作简单,工艺稳定,萃取物得率高。     

超临界CO2萃取铜藻中岩藻黄质的工艺研究

摘 要: 目的 采用超临界CO2流体从铜藻中萃取岩藻黄质。方法 以岩藻黄质提取率为指标,采用单因素试验研究萃取时间、粉碎粒度、萃取压力、萃取温度对超临界CO2流体萃取岩藻黄质的影响。结果 通过正交试验得到最佳提取工艺为:样品粉碎粒度80目,在萃取温度40 ℃、萃取压力25 Mpa下萃取30 min,在最佳萃取条件下,岩藻黄质提取率为 1.12 mg?g-1。结论 优选出超临界二氧化碳萃取铜藻中岩藻黄质的最佳工艺,为进一步开发应用提供参考依据。     

加速溶剂提取法提取赤芍中的芍药苷

目的探讨快速溶剂提取法提取芍药苷的可行性,比较该方法与超声提取法索氏提取法和亚临界水提取法的优越性。方法以芍药苷含量为指标,用单因素考察法对影响加速溶剂提取芍药苷的因素进行优化。结果优选出了加速溶剂提取法提取芍药苷的最佳条件,即以50%乙醇为溶剂,提取温度100℃,提取压力50 kg,流速0.7 ml.min-1,动态提取12 min,收集提取液8 ml。结论加速溶剂提取法可以快速、高效地提取芍药苷。     

Application of dense gas techniques for the production of fine particles

The feasibility of using dense gas techniques such as rapid expansion of supercritical solutions (RESS) and aerosol solvent extraction system (ASES) for micronization of pharmaceutical compounds is demonstrated. The chiral nonsteroidal anti-inflammatory racemic ibuprofen is soluble in carbon dioxide at 35°C and pressures above 90 bar. The particle size decreased to less than 2 μm while the degree of crystallinity was slightly decreased when processed by RESS. The dissolution rate of the ibuprofen (a poorly water-soluble compound) was significantly enhanced after processing by RESS. The nonsteroidal anti-inflammatory drug Cu₂(indomethacin)₄L₂(Cu-Indo); (L=dimethylformamide [DMF]), which possessed very low solubility in supercritical CO₂, was successfully micronized by ASES at 25°C and 68.9 bar using DMF as the solvent and CO₂ as the antisolvent. The concentration of solute dramatically influenced the precipitate characteristics. The particles obtained from the ASES process were changed from bipyramidal to spherical, with particle size less than 5 μm, as the concentration increased from 5 to 100 mg/g. A further increase in solute concentration to 200 mg/g resulted in large porous spheres, between 20 and 50 μ, when processing Cu-Indo by the ASES method. The dissolution rate of the micronized Cu-Indo was significantly higher than the commercial product.     

Selection suitable solvents to prepare paclitaxel-loaded micelles by solvent evaporation method

Amphiphilic block copolymer micelle is one of the most important drug delivery systems to improve the water-solubility of lipophilic drugs. Blank micelles were prepared by solvent evaporation method in order to choose the suitable solvents for PBMA-b-PMPC (poly(n-butyl methacrylate)-b-poly(2-methacryloyloxyethyl phosphorylcholine)) copolymer micelles. The selected solvents, which include chloroform/ethanol mixture and ScCO₂, were used to prepare the paclitaxel-loaded micelles. The micelles with high drug encapsulation efficiency and drug-loading content showed both narrow size distribution and regularly spherical shape. In vitro drug release studies indicated that paclitaxel could be slowly and continuously released from the micelles. More than 50% incorporated drug was released within 132?h from the micelles prepared using ScCO₂ as solvent while only 20% was released at the same period from those prepared using chloroform/ethanol mixture. In addition, the environmentally-friendly solvent, ScCO₂, was used for the first time to prepare the paclitaxel-loaded micelles during the solvent evaporation process.     

Lipid nanoparticle purification by spin centrifugation-dialysis (SCD): a facile and high-throughput approach for small scale preparation of siRNA-lipid complexes

This paper describes the use of Spin Centrifugation-Dialysis (SCD) for small-scale concentration/purification of siRNA-lipid complexes designed for use as therapeutic agents for gene silencing. SCD consists of a two-step method for concentration, filtration and buffer exchange of Lipid Nanoparticles (LNP) to provide a homogeneous preparation suitable for injection. Here, we compare SCD with the more traditionally used Tangential Flow Filtration (TFF), and demonstrate the physicochemical and biological comparability of LNPs produced with both methods. TFF is a highly scalable method used in both developmental and production applications, but is limited in terms of miniaturization. In contrast to TFF, SCD is faster, less expensive, and requires less oversight for assembling LNPs for small-scale applications, such as target screening both in vitro and in vivo. The finding that SCD is a viable method for filtering LNPs in a manner similar to TFF, producing particles with comparable properties and biological activity, is significant given the complexity and sensitivity of LNPs to processing conditions.     

Critical properties of lactide-co-glycolide polymers for the use in microparticle preparation by the aerosol solvent extraction system.

The Aerosol Solvent Extraction System (ASES) process uses supercritical carbon dioxide for the production of microparticles. Since the critical temperature for this gas is at 304 K, polymers that are used in this process must fulfil certain requirements in crystallinity, and thermal behavior. This can be achieved by the use of blocked copolymers and thus the presence of semicrystalline microdomains in the polymers. However, changing the sequences of the comonomers dilactide and lactide often leads to polymers of low solubility due to long glycolide blocks. In this study, the critical properties of two blocked co-polymers were investigated, such as the blocked structure itself by (1)H-NMR and (13)C-NMR, the thermal behavior by differential scanning calorimetry (DSC), and the crystallinity by powder diffraction. The impact of these properties on microparticles formed by those polymers was also object of these studies. Additionally, two different model drugs, albumin and estriolm were embedded to investigate the impact of different polymer properties on drug content and release.     

快速压力溶剂萃取高效液相色谱法测定建泽泻中的萜类成分

目的建立泽泻主要成分23-乙酰泽泻醇B的快速检测方法。方法利用快速溶剂萃取配合高效液相色谱法对23-乙酰泽泻醇B进行含量测定。结果考察快速溶剂萃取仪的两个主要参数：温度和压力,选择60℃,压力1260psi对泽泻23-乙酰泽泻醇B成分进行快速萃取。建立的HPLC方法简单、快速、准确;出峰时间小于20min,分离度良好,峰形尖锐;日间精密度日内精密度：RSD〈5.0%;23-乙酰泽泻醇B在相应的线性范围内r〉0.999;稳定性良好（RSD%〈5.0%）。结论此方法优于传统方法,为评价泽泻的质量提供一种新的技术手段。     

Optimized conditions for the extraction of secondary volatile metabolites in Angelica roots by accelerated solvent extraction

Accelerated solvent extraction (ASE) of three common Angelica species found in Asia: Angelica sinensis (Oliv.) Diels from China, Angelica acutiloba (Sieb. et Zucc.) Kitagawa from Japan, and Angelica gigas Nakai from Korea was investigated. Preliminary experiments, including the selection of the solvent, extraction time, pressure, static cycle and time were investigated to optimize experimental parameters. Kováts indices and mass spectra were used to identify the components in the various fractions. These were then confirmed using gas chromatography–mass spectrometry (GC–MS). A total of 18 compounds were identified, with qualitative differences and similarities observed among the cultivars. From the 18 compounds found in the ASE extract of danggui cultivars, the major components were decursin, decursinol angelate (A. gigas); butylidene dihydrophthalide, 4-hydroxy-4-methyl-2-pentanone (A. sinensis); and 9,12-octadecanoic acid in Angelica acutiloba. The optimum ASE operating conditions were n-hexane as extraction solvent, extraction temperature and pressure of 80 °C and 1500 atm, respectively, static cycle of 2 min, and static time of 10 min. Under these conditions, the percentages of main analytes were increased.     

超声波辅助溶剂萃取西藏和河南藏红花中挥发油的GC-MS分析(英文)

对西藏和河南藏红花中挥发油化学成分进行提取和分析,比较不同溶剂萃取藏红花挥发油化学成分的差异。采用超声波辅助溶剂萃取法提取挥发油,分别采用乙醚、乙醇、乙酸乙酯、二氯甲烷和丙酮5种溶剂萃取后浓缩,通过GC-MS分析,实现对组分的鉴定,同时用峰面积归一化法计算它们的相对含量。结果表明,不同溶剂提取藏红花中挥发油化学成分间存在差异,且西藏和河南藏红花中提取所得挥发性成分的组成和比例也存在差异。超声波辅助溶剂萃取/Gc-MS是一种简单、快速、有效的挥发油成分分析方法。     

ET-AAS determination of aluminium in dialysis concentrates after continuous flow solvent extraction

Conditions of a continuous flow extraction (CFE) of aluminium acetylacetonate in acetylacetone and aluminium 8-hydroxyquinolinate into methylisobutylketone (lengths of reaction and extraction coils, flow rates of aqueous and organic phases and their flow rate ratio, pH of aqueous phase, lengths of coils for transport of aqueous and organic phases and effect of salts) were studied. The analytical signal of the aluminium chelates present in the organic phase was measured at 309.3 nm using atomic absorption spectrometry with electrothermal atomization (ET-AAS) at the flow rate ratio F aq/F org=3 for aqueous and organic phases. The five points calibration curves were linear (R2 0.9973 and 0.9987) up to 21 microgl(-1) Al with the limits of detection of 0.3 microgl(-1) and the recovery 100+/-2% and precision of 3% at 2-10-fold dilution of the dialysis concentrates. The acetylacetonate method was applied to the determination of aluminium in real dialysis concentrates. Aluminium in concentrations 5-6 microgl(-1) (R.S.D.s 5-10% in real samples) were found and the results were in the very good agreement with those obtained by an ET-AAS using preconcentration of Al(III) on a Spheron-Salicyl chelating sorbent (absolute and relative differences were under 0.4 microgl(-1) and 8.2%, respectively).     

天然产物分离中高速逆流色谱溶剂体系的研究进展

根据溶剂体系的极性与分离的天然产物的关系,本文对高速逆流色谱中使用的溶剂系统进行了归纳总结,不仅对快速选择溶剂体系分离天然产物起到了一定的指导作用,而且为今后高速逆流色谱溶剂体系的研究提供了方便。     

不同溶剂及提取方式对沉香精油成分的影响

目的 采用气相色谱-质谱联用法（GC-MS）分析沉香Aquilaria sinensis（Lour.）Gilg精油成分,比较不同溶剂和不同提取方式对沉香精油成分的影响。方法 精密称取3份沉香粉30 g,分别加入150 mL三级水、无水乙醇和石油醚,在50℃下磁力搅拌1.5 h,滤过,滤渣重复以上步骤1次,合并滤液,浓缩得精油;沉香粉分别经超临界提取、连续相变提取、水蒸气提取制备精油;称量精油质量,计算得率。通过气相色谱-质谱联用仪（GC-MS）对挥发性化合物进行鉴定及检测相对含量;通过GC-MS对不同提取方式所得精油中脂肪酸组成进行检测。结果 水、乙醇和石油醚提取精油共检测出191种物质,不同溶剂所得提取物组成差异较大;乙醇提取精油得率最高,为10.70%。超临界、连续相变和水蒸气提取精油共检测出180种物质,连续相变提取所得精油香气成分最多,为90种,且精油得率最高,为1.42%;3种提取方法所得精油共检测到8种脂肪酸,连续相变所得精油脂肪酸种类最多,为8种。结论 不同溶剂和不同方式提取所得成分差异较大,但连续相变提取精油得率高、提取成分多,有利于还原沉香的本身风味,是一种新型有效的提取方式。     

Stability of chitosan-pDNA complex powder prepared by supercritical carbon dioxide process

The present study examined the stability of a gene in powders prepared with supercritical carbon dioxide (CO₂) from the viewpoints of the ternary structure of DNA and in vivo transfection potential. An aqueous chitosan–pCMV-Luc complex solution containing mannitol was injected into the stream of a supercritical CO₂/ethanol admixture to precipitate a gene powder. The obtained gene powders and gene solutions were placed in stability chambers at 25 or 40 °C for 4 weeks. The integrity and transfection potency of the gene were examined by electrophoresis and in vivo pulmonary transfection study in mice. The supercritical CO₂ process decreased the supercoiled DNA during the manufacturing process; however, the decrease in the remaining supercoiled and open circular DNA in the powders during storage was much slower than that in solutions. In addition, the powders had higher transfection potency than the solutions containing the same amount of DNA. The effect of chitosan on the stability of DNA in solutions was not obvious in the solutions but it improved the stability of DNA in powders during manufacturing and storage. Thus, a gene powder with a cationic vector is a promising ready-to-use formulation for inhalation therapy of pulmonary diseases.     

加压溶剂提取-高效液相色谱法测定天然和人工虫草中的麦角甾醇、核苷及其碱基

目的建立同时测定虫草中麦角甾醇、核苷及其碱基含量的简便方法。方法正交法优化加压溶剂提取条件；HPLC法同时测定天然和人工虫草中上述成分的含量。结果以甲醇为提取溶剂，提取温度160 ℃，提取时间5 min，提取压力10 MPa，循环1次，提取1次。采用Zorbax NH₂分析柱(250 mm×4.6 mm ID, 5 μm)，流动相为A(乙腈)-B(10 mmol·L^-1醋酸铵溶液)二元梯度洗脱：0-5.0 min，B%为0→15%；5.0-25.0 min，B%为15%→20%；25.0-35.0 min，B%为20%→ 40%；35.0-45.0 min，B%为40%→ 80%；45.0-50.0 min，B%为80%。结论本法能够快速、简便地测定虫草中麦角甾醇、核苷及其碱基的含量。     

Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil (o/o) solvent evaporation method

Abstract

The objective of this study was to produce biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres by an oil-in-oil (o/o) solvent evaporation method to prolong the in vitro release of ovalbumin (OVA) as a model protein. The effects, on loading efficiency, microsphere yield, morphology and drug release, of two dispersing agents, aluminum tristearate and Span 80, in mineral oil were examined. PLGA 50/50 microspheres containing OVA powder (sieved through a 53 μm mesh) were prepared using an o/o solvent evaporation method. When aluminum tristearate was employed as a dispersing agent, the loading efficiency and yield of OVA had maximum values of 89 and 72% at 0·15% (w/v) aluminum tristearate, respectively. Morphology studies suggested that the obtained microspheres were spherical, and had a smooth surface. The diameters of the microspheres ranged between 100 and 200 μm. The loading efficiency, or yield, for microspheres decreased significantly above or below 0·15% (w/v) aluminum tristearate, and microspheres wkh irregular shapes were observed. The minimum sedimentation volume ratio (F) was obtained at a dispersity of carbon black particles in ethanol containing 0·15% (w/v) aluminum tristearate by a sedimentation study, and the cloudy supernatant suggested a defiocculated suspension. However, on the contrary, when Span 80 was added into the mineral oil as a dispersing agent, the concentration of Span 80 had little or no effect on the characteristics of the prepared microspheres. Drug loadings (60–70%) were obtained within the Span 80 concentrations employed in the present study (0·05–1·0% (w/v)). The yields were also in the same levels. The microspheres prepared in mineral oil containing Span 80 had an average diameter less than 50 μm in all cases. Sustained-release characteristics were demonstrated for PLGA microspheres prepared in mineral oil containing aluminum tristearate as a dispersing agent, even though a burst release at the initial phase was observed. This initial burst release from PLGA microspheres was reduced to some extent by micronization of the OVA powder using a planetary-type ball mill. However, PLGA microspheres prepared in mineral oil containing Span 80 as a dispersing agent, exhibited a large initial burst release. This burst release seems to be due to the smaller size of microspheres and the OVA powder adhering to the surface of PLGA microspheres (confirmed by scanning electron microscope (SEM) study).     

左旋多巴胃漂浮片的制备

目的制备左旋多巴胃漂浮片。方法以HPMC(K4M)、十八醇、丙烯酸树脂(L100-55)、乳糖、硬脂酸镁等辅料与主药左旋多巴采用湿法制粒的方法进行压片,通过正交实验筛选处方。结果筛选出左旋多巴胃漂浮片的优化处方(25片)为:HPMC1.03 g,十八醇0.77 g,丙烯酸树脂2.15 g,乳糖0.9 g。结论制得的胃漂浮片能在模拟胃液中2 min内起漂,体外溶出实验结果满足制剂要求。