超临界流体快速膨胀法制备超细阿昔洛韦粒子

以二氧化碳作为超临界溶剂,采用超临界溶液快速膨胀技术制备得到超细阿昔洛韦药物粒子,在一定的温度和压力情况下,测定了阿昔洛韦在超临界二氧化碳中的溶解度,考察了各种操作参数对药物粒子粒径的影响,研究了药物粒子粒径随各种操作参数的变化规律。结果表明:阿昔洛韦在超临界二氧化碳中的溶解度较小,在10-5~10-6之间(摩尔分率),溶解度随着温度和压力的升高而增大,不存在文献中所报道的反向区。同时实验结果表明:药物粒子粒径变化对预膨胀温度最敏感,粒径随预膨胀温度的升高而减小;一定范围内随收集距离的增大而增大;在萃取温度较低的情况下,粒子粒径基本随着萃取温度的升高而减小;随着萃取温度的升高,在相对较高预膨胀温度下,粒径随着萃取温度升高而增大。     

超临界溶液快速膨胀法制备二氯二茂钛微粒及催化乙烯聚合

为克服茂金属催化剂得到的聚合物形态难以控制、表观密度较低、易粘釜和不适于气相淤浆聚合等缺点,以超临界溶液快速膨胀过程为手段,以期制得颗粒分布均匀的细微催化剂颗粒,继而得到形态良好的聚合物.作为超临界流体技术的基础,首先测定了二氯二茂钛在超临界丙烷中的溶解度.在此基础上,用RESS方法制得了均匀的超细催化剂颗粒,且系统考察了溶液浓度、预膨胀温度、喷嘴结构和接收距离对沉析颗粒粒径的影响.最后,将RESS所制得的催化剂颗粒进行乙烯淤浆聚合,并分析聚合物形态结构.实验结果表明,在温度为383.15～408.15 K和压力为10～35 MPa范围内,溶解度随温度的增加而增加,随压力的升高而增加,说明在该操作范围内,不存在反向区.RESS操作的结果显示,二氯二茂钛颗粒粒径随溶液浓度的增大而减小,随预膨胀温度的升高而增大,而喷嘴直径的减小和喷嘴长度的增加将使得颗粒粒径增大,而收集距离的增加将使得颗粒粒径先增加后减缓,直至不再变化.通过对原始的催化剂颗粒和RESS制得的催化剂颗粒进行乙烯淤浆聚合表征发现,相比于原始催化剂,由于烯烃催化剂的复制原理,RESS制得的催化剂颗粒的聚合物具有良好的形态.     

超临界流体快速膨胀法制备超细氟比洛芬粒子

文章选用二氧化碳作为超临界溶剂,采用超临界溶液快速膨胀技术制备超细氟比洛芬药物粒子,在较宽的温度压力范围内测定了氟比洛芬在超临界二氧化碳中的溶解度,考察了各种操作参数对药物粒子粒径的影响,研究了药物粒子粒径随各种操作参数的变化规律。结果表明：在实验考察的范围内,氟比洛芬的溶解度较小,在10-5~10-7之间（摩尔分率）,溶解度随着温度和压力的升高而增大。同时实验结果表明：粒径随预膨胀压力的升高而减小;一定范围内随接收距离的增大而增大;在萃取温度较低的情况下,粒子粒径基本随着萃取温度的升高而减小;随着萃取温度的升高,在相对较高预膨胀温度下,粒径随着萃取温度升高而增大。     

超临界CO2法制备超细HMX颗粒

考察了预膨胀压力、HMX丙酮溶液初始浓度、取样停留时间及其他因素对制备HMX超细微粒粒度和晶体性质的影响.制备的超细HMX微粒平均粒径在350 nm以下,一部分微粒粒度小于100 nm.结果表明,预膨胀压力对HMX颗粒尺寸的影响较大,压力增加,HMX平均粒度变小,粒度分布变窄;HMX丙酮溶液初始浓度对HMX的粒度和粒度分布有很大影响,初始浓度越小平均粒径就变小,粒度分布变窄.停留时间及喷嘴尺寸对颗粒粒度、粒度分布及其形貌都有不同程度的影响.     

超临界流体技术制备三棕榈酸甘油酯微粒

利用气体饱和溶液微粒形成技术实验装置,分别用超临界N2和超临界Co2制备三棕榈酸甘油酯微粒,探讨压力、温度以及喷嘴大小等工艺参数对微粒（粒径、粒径分布和形貌）的影响。结果表明：N2辅助过程得到的微粒基本为球状;预膨胀压力越高,粒径越小,粒径分布越窄;100μm喷嘴下制得的微粒粒径最小,且分布较均匀。CO2辅助过程得到的微粒部分为球状,部分为针状和片状;预膨胀压力越高,粒径越小,粒径分布越窄;喷嘴直径大小对微粒平均粒径及粒径分布影响不大;预膨胀温度升高,颗粒的粒径稍微增大。CO2辅助过程得到的微粒粒径比N2辅助过程得到的微粒粒径稍大,但两者的粒径分布相差不大。     

碳纳米管超细粉碎分级的特性研究

为了制备超细碳纳米管粉体,利用机械磨和气流磨对碳纳米管粉体进行超细粉碎,通过调控设备运行时分级机和引风机的转速,对不同运行参数下制备的超细碳纳米管的粒度、能耗、形貌特征进行测试与分析。研究发现,常温下气流磨分级机转速在2 100～7 200 r/min时,所制备的碳纳米管细粉粒度d₅₀在10.127～2.540μm;高温（200℃）下气流磨转速在4 800～6 000 r/min时,所制备的碳纳米管细粉粒度d₅₀在5.061～2.831μm。机械磨风量在339.757～688.903 m³/h时,所制备的碳纳米管细粉粒度d₅₀在4.892～11.443μm。当粉碎到相同粒度d₅₀分别为5、10μm时,机械磨的产能分别为气流磨的1.6、2.1倍,而气流磨的单位吨能耗分别为机械磨的3、3.9倍。机械磨粉碎后的碳纳米管颗粒粒度明显减小,大多呈规则形状;气流磨粉碎后的碳纳米管颗粒粒径相对于机械磨粉碎后的颗粒粒度明显减小,大多呈无规则形状。因此,在工业生产中,综合考虑粉碎的粒度、能耗和形...     

阿昔洛韦在超临界CO2中的溶解度与关联

药物微粒化可改善其溶出度,提高生物利用度。为应用超临界流体技术制备阿昔洛韦(Acyclovir)微粒,用静态法测定了在313．15～413．15K,10．0～30．0MPa下阿昔洛韦在超临界CO2中的溶解度。阿昔洛韦的溶解度较小,在10^-5～10^-7(摩尔分率)之间,溶解度随着温度和压力的升高而增大,不存在文献报道的反向区。采用P-R方程对溶解度数据进行关联,平均相对误差为10．0％。     

聚脲微球粒径与形态结构控制研究

通过沉淀聚合制备聚脲微球,主要研究反应时间、反应温度及单体添加量对聚脲微球粒径、粒径分布及形态结构的影响。结果表明,在其他条件不变,反应时间在80～110 min时,聚脲微球的粒径分布呈现双粒径分布,120min时体系为单粒径分布,微球平均粒径由2. 1μm增加到5. 9μm;其他条件不变,反应温度在30～45℃时,粒径由5. 9μm增加到7. 0μm,粒径变异系数(CV)控制在5%以内。当温度到达50℃时,微球CV大于5%;其他条件不变,单体投入量在2%～5%时,微球粒径由5. 8μm逐步增加到8. 4μm,CV小于10%,当质量分数为7%时,CV为52%。通过对反应时间、反应温度及单体添加量的研究,得到了一系列制备粒径及形态可控聚脲微球的规律,为制备出粒径及形态可控的聚脲微球奠定实验和理论基础。     

聚氨酯泡沫模板法低温制备SiC泡沫陶瓷

利用聚氨酯泡沫浸渍聚碳硅烷(PCS)与SiC微粉制成的有机溶剂浆料,挂浆素坯经热氧化处理后于1000℃下惰性气体中烧结制备SiC泡沫陶瓷。运用X衍射分析、扫描电镜、线收缩率测定和三点弯折强度测试等手段,研究了PCS含量、SiC颗粒粒径对泡沫陶瓷线收缩率、微观形貌、抗弯强度的影响。结果表明:PCS经1000℃热解产物为无定形结构,无定形SiC将SiC颗粒粘结起来,形成泡沫陶瓷的骨架筋结构,泡沫陶瓷孔径介于0.3～0.6mm之间;SiC泡沫陶瓷线收缩率随SiC颗粒尺寸与PCS含量的增大而增加,抗弯强度随颗粒尺寸的增加而减小;在颗粒尺寸为0.3μm时,PCS含量为10%时,抗弯强度最大为2.8MPa,当SiC颗粒尺寸为1μm、5μm、10μm和20μm时,PCS含量为15%时,其抗弯强度最大值分别为2.2 MPa、2.1MPa、1.8 MPa和1.4MPa。     

氮气增强溶液雾化技术制备聚乙二醇微粒

以超临界流体增强溶液分散技术为基础,用N2取代C02以实现该过程更好的雾化效果.实验研究以聚乙二醇(PEG6000)/丙酮溶液制备PEG微颗粒,探讨预膨胀压力和溶液流量对粒径及粒径分布的影响.结果表明,超临界N2增强的溶液雾化技术可以制得形态基本上为球形的PEG微粒,并且粒径分布可以方便地控制在1～5μm.PEG微粒随预膨胀压力增大而减少,粒径分布变窄;低PEG/丙酮溶液流量下制备的微粒粒径分布较窄.     

Investigation of the rapid expansion of supercritical solution parameters effects on size and morphology of cephalexin particles

The particle size of organic and inorganic materials is vital parameter to determine its final use. Most of the newly developed pharmaceutical materials are poorly soluble or insoluble in the aqueous media such as biological fluids. Particle size reduction of such pharmaceuticals is one of the clues to improve the dissolution rate, adsorption and bioavailability. In this study, the effect of extraction and expansion parameters of the RESS process such as extraction temperature (313–333 K), extraction pressure (140–230 bar), effective nozzle diameter (450–1700 μm), nozzle length (2–15 mm) and spraying distance (1–7 cm) on the size and morphology of the precipitated particles of cephalexin were investigated. The morphology and particle size of the unprocessed and processed (precipitated) particles were examined by the SEM images. The mean particle size of the precipitated particles was between 0.86 and 7.22 μm depending upon the different experimental conditions used. The precipitated cephalexin particles were close to spherical form while the unprocessed particles were irregular or needle in shape.     

用含夹带剂丙酮的超临界CO2快速膨胀法制备灰黄霉素的微细颗粒

Griseofulvin (GF) is an antifungal drug whose pharmaceutical activity can be improved by reducingparticle size. In this study the rapid expansion of supercritical solution (RESS) was employed to micronize GF.Carbon dioxide with cosolvent acetone was chosen as a supercritical mixed solvent. The solubility of GF in super-critical CO2 with cosolvent acetone was measured using a dynamic apparatus at pressures between 12 and 32 MPa,temperatures at 313, 323 and 333K and cosolvent concentration at 1.5, 3.0, 4.5 and 6.0% (by mole). The effect ofpre-expansion pressure, extraction temperature, spraying distance, nozzle size and concentration of cosolvent on theprecipitated particles was investigated. The results show that the mean particle size of griseofulvin precipitated byRESS was less than 1.2 μm. An increase in pre-expansion pressure, extraction temperature, spraying distance andconcentration of cosolvent resulted in a decrease in particle size under the operating condition studied. With thedecrease of nozzle diameter the particle size reduces. The crystallinity and melting point of the original material andthe processed particle by RESS were tested by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).No evident modification in the crystal habit was found under the experimental conditions tested. The morphologyof particles precipitated was analyzed by scanning electron microscopy (SEM).     

超临界流体溶液快速膨胀法制备灰黄霉素微细颗粒

研究了通过超临界流体溶液快速膨胀 (RESS)技术制取灰黄霉素微细颗粒的过程 .在自行设计的实验装置上研究了RESS过程各操作变量对所制得的灰黄霉素颗粒粒度的影响 .研究结果表明 ,采用RESS方法可以制得符合粒度要求的灰黄霉素微细化产品     

Preparation and Characterization of Micronized Artemisinin via a Rapid Expansion of Supercritical Solutions (RESS) Method

The particle sizes of pharmaceutical substances are important for their bioavailability. Bioavailability can be improved by reducing the particle size of the drug. In this study, artemisinin was micronized by the rapid expansion of supercritical solutions (RESS). The particle size of the unprocessed white needle-like artemisinin particles was 30 to 1200 μm. The optimum micronization conditions are determined as follows: extraction temperature of 62 °C, extraction pressure of 25 MPa, precipitation temperature 45 °C and nozzle diameter of 1000 μm. Under the optimum conditions, micronized artemisinin with a (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA), extraction temperature and pressure have significant effects on the MPS of the micronized artemisinin. The particle size of micronized artemisinin decreased with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS, FTIR, DSC and XRD allowed the comparison between the crystalline initial state and the micronization particles obtained after the RESS process. The results showed that RESS process has not induced degradation of artemisinin and that processed artemisinin particles have lower crystallinity and melting point. The bulk density of artemisinin was determined before and after RESS process and the obtained results showed that it passes from an initial density of 0.554 to 0.128 g·cm(-3) after the processing. The decrease in bulk density of the micronized powder can increase the liquidity of drug particles when they are applied for medicinal preparations. These results suggest micronized powder of artemisinin can be of great potential in drug delivery systems.     

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.     

Micronization of creatine monohydrate via Rapid Expansion of Supercritical Solution (RESS)

In the pharmaceutical industry, an even greater number of products are in the form of particulate solids. In the case of pharmaceutical substances the particle size is quite important since it can limit the bioavailability of poorly water soluble drugs. Since the mid-1980s, a new method of powder generation has appeared involving crystallization with supercritical fluids. In this study, RESS was used to micronize the creatine monohydrate particles. The RESS 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. In addition, the effect of six different RESS parameters including, extraction temperature (313-333 K), extraction pressure (140-220 bar), nozzle length (2-15 mm), effective nozzle diameter (450-1700 μm), spraying distance (1-7 cm) and pre-expansion temperature (353-393 K) were investigated on the size and morphology of the precipitated particles of creatine monohydrate. The characterization (size and morphology) of the precipitated particles of creatine monohydrate was determined by scanning electron microscopy (SEM). The results show great reduction in the size of the precipitated particles of creatine monohydrate (0.36-9.06 μm) compared with the original particles of creatine monohydrate. Moreover, a slight change into spherical form was observed for the precipitated particles of creatine monohydrate while the original particles were irregular in shape.     

Preparation of anthracene fine particles by rapid expansion of a supercritical solution process utilizing supercritical CO<Subscript>2</Subscript>

The rapid expansion of a supercritical solution (RESS) process is an attractive technology for the production of small, uniform and solvent-free particles of low vapor pressure solutes. The RESS containing a nonvolatile solute leads to loss of solvent power by the fast expansion of the supercritical solution through an adequate nozzle, which can cause solute precipitation. A dynamic flow apparatus was used to perform RESS studies for the preparation of fine anthracene particles in pure carbon dioxide over a pressure range of 150–250 bar, an extraction temperature range of 50–70 °C, and a pre-expansion temperature range of 70–300 °C. To obtain fine particles, 100, 200 and 300 μm nozzles were used to disperse the solution inside of the crystallizer. Both average particle size and particle size distribution (PSD) were dependent on the extraction pressure and the pre-expansion temperature, whereas extractor temperature did not exert any significant effect. Smaller particles were produced with increasing extraction pressure and preexpansion temperature. In addition, the smaller the nozzle diameter, the smaller the particles and the narrower the PSD obtained.     

Micronization of salicylic acid and taxol (paclitaxel) by rapid expansion of supercritical fluids (RESS)

The particle sizes of the pharmaceutical substances are important for their bioavailability. The bioavailability can be improved by reducing the particle size of the drug. In this study, salicylic acid and taxol were micronized by the rapid expansion of supercritical fluids (RESS). Supercritical CO₂ and CO₂ + ethanol mixture were used as solvent. Experiments were carried out to investigate the effect of extraction temperature (318–333 K) and pressure (15–25 MPa), pre-expansion temperature (353–413 K), expansion chamber temperature (273–293 K), spray distance (6–13 cm), co-solvent concentration (ethanol, 1, 2, 3, v/v, %) and nozzle configuration (capillary and orifice nozzle) on the size and morphology of the precipitated salicylic acid particles. For taxol, the effects of extraction pressure (25, 30, 35 MPa) and co-solvent concentration (ethanol, 2, 5, 7, v/v, %) were investigated. The characterization of the particles was determined by scanning electron microscopy (SEM), optical microscopy, and LC–MS analysis.The particle size of the original salicylic acid particles was L/D: 171/29–34/14 μm/μm. Depending upon the different experimental conditions, smaller particles (L/D: 15.73/4.06 μm/μm) were obtained. The particle size of taxol like white crystal powders was reduced from 0.6–17 μm to 0.3–1.7 μm The results showed that the size of the precipitated salicylic acid and taxol particles were smaller than that of original particles and RESS parameters affect the particle size.     

Formation of ultrafine aspirin particles through rapid expansion of supercritical solutions (RESS)

The performance of pharmaceuticals in biological systems can be enhanced by reducing the particle size of pharmaceuticals. Rapid expansion from supercritical solution (RESS) has provided a promising alternative to comminute contaminant-free particles of heat-sensitive materials such as drugs. In this work, aspirin has been successfully precipitated by the RESS technology. The performances of the RESS process under different operating conditions are evaluated through the analysis of the particle characteristics. Our results show that extraction pressure and extraction temperature can significantly affect the morphology and size of the precipitated particles whereas the nozzle diameter and pre-expansion temperature are not observed to apparently influence the RESS particles. The RESS process could produce ultrafine spherical particles (0.1-0.3 μm) of aspirin as reflected by SEM observations.