About consistency of Solid's solubility data in supercritical CO2 and some thermodynamic properties estimation

In chemical industry, usual solvents are being replaced by supercritical fluids. Last few years, extraction by these environmentally benign solvents has had much attention and now is considered as the newest separation technology. However, developing new applications and improving existing ones is based on a set of thermodynamic and physical properties of pure solutes related to phase equilibrium for which experimental values cannot be found and consequently, there is an increase need for accurate estimates of these properties. This paper is interested firstly to a thermodynamic property which is the Krichevskii parameter and secondly to a thermophysical one which is the sublimation pressure. First parameter is considered as a governor of thermodynamic properties in binary dilute mixtures near the solvent's critical point and can be calculated from some rigorous relationships and in this paper a review and a new way for its estimation are presented based on consistency of solid's solubility data in supercritical fluids and dilute solution theory. Second parameter is considered as the predominant influencer on solubility in supercritical fluids and unavailability of its experimental values presents an obstacle to thermodynamic modeling of solubility data. For this reason and as a second step, in this paper we present a new manner for its estimation. Obtained results are relevant, very promising for each considered property and the methodology can be applied for other solutes with more complex structures as Pharmaceuticals (antibiotics, drugs, anti-inflammatories …), polycyclic aromatic hydrocarbons (PAHC) and dyestuffs.     

A supercritical fluid-based coating technology. 2: Solubility considerations

Solubility measurements of candidate coating materials have been performed in supercritical (SC) CO₂ so as to select appropriate coating materials for implementation of a solvent-free coating process previously described. Solubility of lipidic compounds such as waxes (paraffin, beeswax, Carnauba wax), pure triglycerides (tricaprin, trimyristin, tripalmitin, tristearin) and mixture of glycerides and fatty acid esters (Gelucire®) in SC CO₂ were evaluated in a static mode under different temperature and pressure conditions, ranging from 13–52°C and from 50–220 bar, whether the CO₂ was in its liquid or SC state. It was shown that the compounds which are mixtures of various components give rise to a selective extraction of the lower melting point components, as evidenced from thermal analysis of soluble and insoluble fractions of the coating materials.     

Bioactive insulin microparticles produced by supercritical fluid assisted atomization with an enhanced mixer

Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA–HCM) was used to micronize insulin from aqueous solution without use of any organic solvents. Insulin microparticles produced under different operating conditions including solution type, solution concentration and precipitator temperature presented distinct morphologies such as highly folded, partly deflated, corrugated or smooth hollow spherical shape. Solution concentration had a striking influence on particle size, and insulin microparticles produced from acidic solution had mean diameters increasing from 1.4 μm to 2.7 μm when protein concentration increased from 3 g/L to 50 g/L. HPLC chromatograms showed no degradation of insulin after SAA–HCM processing and FTIR, CD and fluorescence data further confirmed the structural stability. TGA analysis revealed that insulin microparticles remained moderate moisture content compared with raw material. In vivo study showed that insulin processed by SAA–HCM from acidic solution retained identical bioactivity. SAA–HCM is demonstrated to be a very promising process for insulin inhaled formulation development.     

Progress involving new techniques for liposome preparation

The article presents a review of new techniques being used for the preparation of liposomes. A total of 28 publications were examined. In addition to the theories, characteristics and problems associated with traditional methods, the advantages and drawbacks of the latest techniques were reviewed. In the light of developments in many relevant areas, a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods. However, there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed. Generally speaking, due to the introduction of these latest techniques, liposome preparation is now an improved procedure. These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.     

Characterization of azacytidine/poly(l-lactic) acid particles prepared by supercritical antisolvent precipitation

A controlled azacytidine release system based on drug encapsulation with a polymer material has been prepared and characterized. The drug systems were prepared by precipitation from solutions, using supercritical CO₂ antisolvent technique operating in a semi-continuous mode. Azacytidine was dissolved in dimethylsulfoxide and poly-lactic acid in methylene chloride. The two solutions were mixed before being sprayed into the supercritical reactor. Experimental conditions were 40 °C for temperature, 11 MPa for pressure, and a CO₂ flow rate of 30 ml min⁻¹. The precipitated drug–polymer particles were further characterized to determine the percentage of encapsulated drug and establish the delivery kinetics under various release conditions. A sustained delivery of the drug over a period of various hours was obtained. Besides, an improved stability of the coated drug with respect to the pure azacytidine was found, thus proving the suitability of this approach for dealing with unstable compounds.     

超临界二氧化碳萃取联合色谱法测定益母草注射液中的总生物碱

目的构建超临界二氧化碳（CO2）苹取益母草注射液中总生物碱的方法,定量分析其盐酸水苏碱含量,为建立益母草注射液质量标准提供依据。方法应用超临界CO2萃取益母草注射液中总生物碱,以Spherisorb SCX色谱法定量测定益母草沌射液中盐酸水苏碱含量,色谱条件,Spherisorb SCX（250mm×4．6mm）色谱柱,以磷酸二氢钠溶液0．01mol／L（pH值为5．5）为流动相,柱温25℃,检测波长192mm,流速1．0ml／min,进样量为20μl。结果盐酸水苏碱进样量范围存0．6～5．0μg内,具有显著的线性关系,r=0．870,样品加样平均同收率为101．5％（n=8）。RDS=1．16％。结论超临界CO2萃取法简便稳定,结果可靠,可重复性强,是控制该制剂质量的优良方法。     

Chiral interconversion monitoring of a drug candidate by supercritical fluid chromatography (SFC)

Stereoisomer interconversion of chiral drug substances is of significant importance if it occurs within pharmacological and pharmaceutical time scales and under physiological and shelf life conditions. Several analytical techniques exist for the determination of first order rate constants and enantiomerization energy barriers by dynamic and stopped flow chromatography, mathematical models and functions, and computer programs. The focus of this work is to utilize a simple supercritical fluid chromatography (SFC) chiral assay to determine the possibility of interconversion of the desired R and less active S isomers of a drug candidate. The rate constants of racemization and enantiomerization, the half life of racemization, and enantiomerization energy barriers were determined for the R → S (or, forward) and S → R (or, reverse) conversions. The method was selective and sensitive enough to detect less than 1% interconversion occuring under the conditions studied. The method also demonstrated that R ? S racemization was possible only under extreme conditions of prolonged heating (80 °C) and highly basic pH (9.5).     

超临界CO2萃取-高速逆流色谱快速分离制备板蓝根中的表告依春

目的：建立从板蓝根中快速分离制备高纯度表告依春的方法。方法：板蓝根药材粉碎后采用超临界CO2萃取法提取表告依春粗提物,选择萃取温度、物料粒度、萃取时间和萃取压力为因素进行正交实验优选出超临界液CO2萃取的最佳工艺条件：即萃取压力20MPa,萃取温度为50℃,萃取时间为60 min,物料粒度40～60目。萃取得到的表告依春粗提物采用高速逆流色谱法进行分离制备,两相溶剂体系为乙酸乙酯-正丁醇-甲醇-水（9∶1∶2∶9,v/v）,进样量为400mg,得到纯度为99.6%的表告依春103.7mg。结论：该方法简便、快速、低能耗、回收率高,为板蓝根中表告依春单体的制备提供了新方法。     

超临界二氧化碳萃取丹酚酸B的提取工艺研究

目的 研究超临界CO2中加入非离子表面活性剂的多元醇混合体系萃取丹酚酸B的新工艺.方法 以丹酚酸B的提取率为指标,采用正交实验法进行丹参提取工艺的优选,采用HPLC法测定其含量.结果 超临界CO2萃取中加入非离子表面活性剂的多元醇混合体系可大大提高丹酚酸B的提取率.在本实验条件下,丹参的超临界萃取最佳工艺为:夹带剂选择10%乙醇+5%吐温-80,用量与药材相等,萃取温度55℃,压力30 MPa,萃取时间1.5 h.结论 加入非离子表面活性剂的多元醇混合体系比只用乙醇作夹带剂进行超临界CO2提取丹酚酸B的效率高约6倍.     

夹带剂在超临界CO2萃取中药有效成分中的应用

目的 探讨夹带剂在超临界CO2萃取中药有效成分的规律.方法 就夹带剂对SC-CO2溶解性的影响;夹带剂提高SC-CO2萃取率的原理、计算方法;夹带剂在SC-CO2萃取、精制中药有效成分、除中药中重金属的应用论文进行了综述.结果 夹带剂能改变超临界CO2的溶解性,选择合适的夹带剂及用量能够大幅度提高萃取效率.结论 夹带剂的加入扩大了超临界CO2的萃取范围,值得更广泛应用.