Advances in Supercritical Fluid Crystallization

The supercritical fluid crystallization technique is a novel technology for preparing ultrafine particles. This paper introduced the concept and features of the technique with an emphasis on three kinds of supercritical fluid crystallization techniques, i.e. rapid expansion of supercritical solutions, supercritical fluid anti-solvent and particles from gas saturated solutions Some questions and the prospect of this technique were also discussed.

Supercritical Antisolvent-based Technology for Preparation of Vitamin D3 Proliposome and Its Characteristics

Vitamin D3 （VD3） proliposomes （VDP）, consisted of hydrogenated phosphatidycholine （HPC） and VD3, were prepared using supercritical anti-solvent technology （SAS）. The effects of operation conditions （temperature, pressure and components） on the VD3 loading in VDP were studied. At the optimum conditions of pressure of 8.0 MPa, temperature of 45 ℃, and the mass ratio of 15.0% between VD3 and HPC, the VD3 loading reached 12.89%. VD3 liposomes （VDL） were obtained by hydrating VDP and the entrapment efficiency of VD3 in VDL reached 98.5%. The morphology and structure of VDP and VDL were characterized by SEM （scanning electron micro-scope）, TEM （transmission electron microscope） and XRD （X-ray diffractometer）. The structure of VD3 nanoparti-cles in HPC matrix was formed. The size of VDL with an average diameter of about 1μm was determined by dynamic light scattering instrument （DLS）. The results indicated that VDP can be made by SAS and VDL with high entrapment efficiency can be formed easily via the hydration of VDP.

Preparation and characteristics of nano-crystalline Cu-Ce-Zr-O composite oxides via a green route: supercritical anti-solvent process

The nano-crystalline Cu-Ce-Zr-O composite oxides were successfully prepared by the supercritical anti-solvent （SAS） process. The physicochemical properties and catalytic performances were investigated by X-ray diffraction （XRD）, Raman spectroscopy, H2 temperature-programmed reduction （H2 -TPR）, oxygen storage capacity （OSC） measurement and catalytic activity evaluation. It was found that Cu2＋ ions incorporated into CeO2 -ZrO2 lattice to form Cu-Ce-Zr-O solid solution associated with the formation of oxygen vacancies. The Cu-Ce-Zr-O catalysts prepared via the SAS process with the Cu content 2.63 mol.% showed the highest OSC index of 636.9 μmol/g. Compared with the samples prepared by impregnation method, Cu doping using SAS process could improve the dispersion of Cu2＋ in the composite oxide, enhance the interaction between Cu2＋ and CeO2-ZrO2 , improve the reducibility of catalyst, and thus improve the OSC performance and increase the catalytic activity for CO oxidation at low temperature.

Structures and oxygen storage capacities of CeO_2-ZrO_2-Al_2O_3 ternary oxides prepared by a green route:supercritical anti-solvent precipitation

CeO2-ZrO2-Al2O3 ternary oxides were successfully prepared by a green route of supercritical anti-solvent precipitation with supercritical CO2 as anti-solvent and methanol as solvent. The structures and oxygen storage capacities of these ternary oxides were characterized by XRD, Raman spectra and oxygen storage capacity measurements. It was found that Al3＋ and Zr4＋ inserted into CeO2 lattice, forming CeO2-ZrO2-Al2O3 solid solution. The concentration of aluminium isopropoxide in the solution affected the concentration of oxygen vacancy and the distortion of oxygen sublattice which were responsible for the oxygen storage capacity. The rapidest oxygen uptake/release rate and maximum total oxygen storage capacity （122.0 mmolO2/molCeO2） were obtained with the aluminitun isopropoxide concentration at 0.2 wt.% in the solution.

Enhancing the stability of astaxanthin by encapsulation in poly (1-lactic acid) microspheres using a supercritical anti-solvent process

To improve the physicochemical properties of astaxanthin, it was encapsulated in poly (1-lactic acid)(PLLA) using a supercritical anti-solvent (SAS) process with dichloromethane/acetone mixture as the solvent, and supercritical CO2 as the anti-solvent. The effects of altering five SAS operating cond让ions, solvent ratio, temperature, pressure, concentration of carrier, and flow rate, on the microstructure of particles were investigated using an orthogonal experimental design. Under the optimal conditions, astaxanthin/PLLA particles were produced with an encapsulation efficiency of 91.5% and a mean particle size of 954.6 nm. SEM images showed that most astaxanthin/PLLA particles were uniform microspheres. FT-IR spectra showed that the chemical structure of astaxanthin was unchanged by the SAS process. The results of chromatic difference, X-ray diffraction, thermogravimetric, and differential scanning calorimetry analyses showed that astaxanthin had been encapsulated in the PLLA matrix in an amorphous state. Overall, astaxanthin/PLLA microspheres greatly enhanced the stability of astaxanthin during storage, and the levels of residual solvents were far lower than the ICH lim让s. This means that astaxanthin/PLLA microspheres prepared using SAS show great potential for use in many food, cosmetic, and pharmaceutical formulations.

Hollow nano-particles formation for CuO-CeO2-ZrO2 via a supercritical anti-solvent process

Hollow CuO-CeO2-ZrO2nano-particles were prepared with supercritical anti-solvent apparatus by using methanol as sol-vent and supercritical carbon dioxide as anti-solvent. Two key factors （i.e., pressure and temperature） were investigated to explore the effects of catalyst structure and physic-chemical properties （i.e., morphology, reducing property, oxygen storage capacity and specific surface area）. The resulting materials were characterized with X-ray diffraction （XRD）, high resolution transmission electron micros-copy （HRTEM）, Brunauer-Emmett-Teller （BET）,hydrogen temperature programmed reduction （H2-TPR） and oxygen storage capac-ity （OSC） measurement, respectively. The experimental results showed that lower temperatures promoted production of hollow struc-ture nano-particulates. The particle morphology also changed significantly, i.e. the solid construction was first transferred to hollow structure then back to solid construction. The optimal conditions for obtaining hollow nano-particles were determined at 45 °C, 18.0–24.0 MPa.

Micronization of curcumin with biodegradable polymer by supercritical anti-solvent using micro swirl mixer

Curcumin is a hydrophobic polyphenol compound exhibiting a wide range of biological activities such as anti-inflammatory, anti-bacterial, anti-fungal, anti-carcinogenic, anti-human immunodeficiency virus, and antimicrobial activity. In this employed to produce the work, a swirl mixer was micronized curcumin with polyvinylpyrrolidone （PVP） by the supercritical antisolvent process to improve the bioavailability of curcumin. The effects of operating parameters such as curcumin/PVP ratio, feed concentration, temperature, pressure, and CO2 flow rate were investigated. The characterization and solubility of particles were determined by using scanning electron microscopy, Fourier Transform Infrared spectroscopy, and ultra-violet-visible spectroscopy. The result shows that the optimal condition for the production of curcumin/PVP particles is at curcumin/PVP ratio of 1：30, feed concentration of 5 mg·mL^-1, temperature of 40 ℃, pressure of 15 MPa, and CO2 flow rate of 15 mL·min^-1. Moreover, the dissolution of curcumin/PVP particles is faster than that of raw curcumin.

超临界抗溶剂法制备吲哚美辛微粒的工艺研究

采用超临界CO_2抗溶剂法制备吲哚美辛微粒,以微粒的体积平均粒径为评价指标,在单因素试验的基础上设计正交试验优选吲哚美辛微粒的制备工艺,并考察其体外溶出速率及溶出度。结果表明在最优条件下可制备得到粒径明显小于原料的吲哚美辛微粒,SEM显示吲哚美辛微粒呈纤维状;FTIR、DSC及XRD观察结果表明吲哚美辛微粒未发生化学结构的改变;体外溶出测试显示吲哚美辛优选工艺微粒的溶出速率明和溶出度显高于原料药的溶出速率和溶出度。

Supercritical Fluid Media in Challenges of Substance and Material Dispersion

The paper deals with the problem of material dispersion using supercritical fluid media. At the same time, emphasis is made on modifications(SAS, GAS, SEDS and ASES) of the supercritical fluid anti-solvent method of dispersion. The results of SAS method implementation for dispersion of pure polycarbonate and polycarbonate doped with "CdSe/CdS-core/shell" quantum dots(carried out in the pressure range of 8.0-25.0 MPa at temperatures of 313.15 K and 358.15 K) are submitted. The range of the operating parameters has been established through the example of pure polycarbonate dispersion, which provides the production of nanoparticles with the size range of 10-100 nm. Encapsulation of Cd Se/Cd S quantum dots into polycarbonate using the SAS method has no effect on optical properties of the encapsulated quantum dots. The results of paracetamol dispersion using the SEDS method are presented. The effect of operating conditions of the paracetamol dispersion process on morphology of the obtained product is described. Co-dispersion of ethylene–vinyl acetate copolymers and low-density polyethylene mixtures by SEDS method has been carried out under pressures of 8.0-25.0 MPa at temperatures of 313 K, 323 K, and 333 K. The comparison of melting and crystallization between the resulting copolymer mixtures and mixtures with the same composition obtained by mixing in the liquid melt, has shown that implementation of SEDS results in an increase of crystallinity degree of the polymer mixtures.

超临界CO_2抗溶剂法制备芹菜素微粒的工艺研究

目的采用超临界CO2抗溶剂法制备芹菜素微粒,以微粒的平均粒径为评价指标,在单因素试验的基础上设计正交试验优选芹菜素微粒的制备工艺,并考察其体外溶出速率。方法对微粒进行粒度分布、扫描电镜(SEM)分析、傅里叶红外吸收光谱(FTIR)检测及差示扫描量热(DSC)法以验证优选的最佳工艺;进行芹菜素原料与芹菜素优选工艺微粒的体外溶出测试。结果正交试验得出的优选工艺条件:丙酮及二甲基亚砜共溶剂比例为24∶1,结晶温度40℃,结晶压力10 MPa,溶液体积流量2.0 mL/min,芹菜素质量浓度8 mg/mL;在此条件下可制备得到粒径明显小于芹菜素原料的芹菜素微粒,SEM显示芹菜素微粒呈不规则状;FTIR与DSC观察结果表明芹菜素微粒未发生化学结构的改变;体外溶出测试显示芹菜素优选工艺微粒的溶出速率明显高于原料药的溶出速率。结论超临界CO2抗溶剂法可用于制备芹菜素微粒,且可推测经处理后的芹菜素生物利用度提高,为制备超细微粒提供参考。

Protein microspheres for pulmonary drug delivery

A new supercritical fluid(SCF)technique was developed for the preparation of microspheres for pulmonary drug delivery(PDD).This technique,based on the anti-solvent process,has incorporated advanced engineering design features to enable improved control of the particle formation process.Human recombinant insulin(HRI)was used as a model compound to evaluate the efficiency of this SCF process.An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water,leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.