Design and characteristic analysis of a new nozzle for preparing microencapsulated particles by RESS

A new nozzle was designed for the technology of making microencapsulated particles by rapid expansion of supercritical solution (RESS). The design is based on the theory of gas dynamics in which the potential energy of high stagnation pressure is converted totally into effective velocity energy. Therefore, a high momentum of the exit jet can be obtained for improving the capability of removing molten debris quickly. Furthermore, the microencapsulated red phosphorus particles were prepared by RESS with the new nozzle, and the structure and property of the microencapsulated red phosphorus particles were characterized by the SEM images, droplet concentration distributions, and moisture absorption ratio. The results show that the process can effectively encapsulate the red phosphorus particles with the paraffin.     

酚醛树脂为囊壁的超细微胶囊红磷制备及其表征

通过原位聚合法制备了酚醛树脂(PF)为囊壁、红磷为囊芯的超细微胶囊红磷（MRP）阻燃剂。采用傅里叶红外（FTIR）光谱仪、扫描电子显微镜、X射线光电子能谱、激光粒度分布仪、热重分析对MRP进行表征,测试了MRP的吸湿性、抗氧化性等基本性能,并讨论了制备MRP的主要影响因素。结果表明, MRP平均粒径为7.5 μm,表面包覆紧密;着火点提高至485 ℃,且热稳定性得到提高;其吸湿率小于1.8 %,抗氧化性小于7.8 mg/g·h,磷化氢的释放小于3.6 μg/g·h,均比红磷有显著的提高。     

Preparation of cefuroxime axetil nanoparticles by rapid expansion of supercritical fluid technology

As a poorly water-soluble drug, cefuroxime axetil (CFA) features a low solubility and dissolution rate in the gastrointestinal tract, which limits its effective absorption and bioavailability. The objective of this study was production of amorphous CFA nanoparticles directly without any additive by rapid expansion of supercritical solution technology. The effects of process parameters, such as the temperature of nozzle (50-70 °C) and extraction port (60-90 °C) were investigated each in three levels, on the properties of the formed particles by a full factorial design. The particles were then analyzed for differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential and dissolution properties. Z-average particle size of different nanoparticles was between 158 and 513 nm and zeta potential also changed from − 4.29 to − 42.8 mV. The lowest particle size was seen in sample with nozzle temperature at 60 °C and the extraction temperature at 90 °C. However, when temperatures of nozzle and extraction column were decreased to 50 °C and 75 °C respectively, the particle size was increased to 465 nm. More than 90% of the some nano-sized CFA formulations were dissolved in 3 min and complete dissolution occurred within 20 min, while the commercial CFA did not achieve complete dissolution (only about 50%) during 60 min of the testing period.     

Micronization of ketoprofen by the rapid expansion of supercritical solution process

The particle size of the pharmaceutical substances is important for their bioavailability (the percentage of the drug absorbed compared to its initial dosage). The absorption rate can be increased by reducing particle size of the drug particles. This study was conducted to investigate the effects of the extraction pressure (140–220 bar), extraction temperature (308–338 K), nozzle length (2–15 mm), effective nozzle diameter (450–1700 μm), and collection distance (1–10 cm) on the size and morphology of the precipitated ketoprofen particles. The characterization (size and morphology) of the particles was investigated using scanning electron microscopy (SEM). The average particle size of the original material was 115.42 μm, while the average particle size of the micronized particles is between 0.35 and 7.03 μm near to quisi-spherical, needle and irregular shape depending upon the experimental conditions.     

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.     

Preparation of microencapsulated red phosphorus through melamine cyanurate self‐assembly and its performance in flame retardant polyamide 6

A novel technology was developed to prepare microencapsulated red phosphorus (RP) with a coating of melamine cyanurate (MCA) serving as both a nitrogen‐containing flame retardant and as a solid lubrication agent. We took advantage of the self‐thickening effects during the MCA self‐assembly process to realize effective encapsulation on the surface of predispersed RP powder. The technology described in this article can overcome several drawbacks of current microencapsulation processes including (1) relatively complicated preparation processes, (2) use of formaldehyde or other noxious modifiers, and (3) poor compatibility with flame retardant fillers and polymer matrix resulting in poor physical properties. Additionally, this novel technology can also modify various properties of RP with regard to lubrication performance, ignition point, moisture absorption ratio, and color. As a composite system of flame retardant phosphorus encapsulated by a nitrogen‐containing flame retardant, the microencapsulated RP showed nitrogen‐phosphorus (N‐P) synergism with further improved flame retardancy. The action and mechanisms of the microencapsulated RP flame retardant polyamide 6 (PA6) were investigated by limiting oxygen index, vertical burning experiment (UL94), thermogravimetric analysis, and scanning electron microscope observations. The results indicated that the flame retardant PA6 possessed desired flame retardancy because of effective char‐formation of the condensed phase and it also showed satisfactory mechanical properties as the result of the good compatibility between flame retardant and PA6 resin. POLYM. ENG. SCI., 46:1548–1553, 2006. © 2006 Society of Plastics Engineers     

三聚氰胺甲醛树脂包覆不同目数红磷的稳定化研究

采用原位聚合方法制备了三聚氰胺甲醛树脂包覆不同目数的红磷.对包覆红磷进行了扫描电镜、X射线光电子能谱(XPS)、吸水性、抗氧化性、pH值及热重分析测试.扫描电镜和XPS结果表明,三聚氰胺甲醛树脂在红磷表面形成了有效包覆.吸水率结果表明,三聚氰胺甲醛树脂包覆后的红磷,其吸水率随着时间增长显著降低,7d后的吸水率低于0.6...     

Supercritical fluid extraction from Priprioca: Extraction yield and mathematical modeling based on phase equilibria between solid and supercritical phases

This study aimed to investigate the supercritical carbon dioxide extraction of Cyperus articulatus L. (Priprioca). Before the experiments were performed, the raw material was cleaned, vacuum packed and maintained at −5 °C. The moisture content of the material was determined using an oven with forced air circulation operating at 105 °C. The material was then ground, and the mean diameter of the resulting particles was determined using a set of standard sieves. Extraction was performed at pressures of 100–300 bar, temperatures of 40–50 °C, and extraction times up to 240 min using supercritical carbon dioxide as the solvent. For each load, approximately 50 g of Priprioca was packed into the extractor. According to the experimental results, the yields of extraction were significantly influenced by pressure and temperature. Additionally, this paper provides a mathematical model of the supercritical extraction of Priprioca. The employed mathematical model was based on the mass conservation law, which included two partial differential equations for the solute concentration in the solid and fluid phases. By applying a novel method, the distribution coefficient of the extract between supercritical fluid and solid phases was obtained using the criterion of equal fugacity at equilibrium. The model-predicted extraction yield was then compared with the corresponding experimental data. Additionally, the reasons for the deviations between the model and the experimental data under certain operational conditions are discussed.     

Formation of deagglomerated PLGA particles and PLGA-coated ultra fine powders by rapid expansion of supercritical solution with ethanol cosolvent

Rapid expansion of supercritical solution (RESS) was used for preparing polymer particles and polymer coating of ultra fine powders. The polymer of pharmaceutical interest was Poly(lactic-co-glycolic acid) (PLGA with PLA: PGA ratio of 85: 15 and MW of 50,000–75,000) and the simulated core particles were 1.4-μm SiO₂ and 70-nm TiO₂ particles. The supercritical solution was prepared by dissolving PLGA in supercritical carbon dioxide with ethanol as a cosolvent. Supercritical solution of CO₂-PLGA was sprayed through capillary nozzles to ambient conditions, resulting in formation of submicron PLGA particles. Similarly, rapid expansion of supercritical solution of CO₂-PLGA suspended with the core particles could provide solvent evaporation and deposition of submicron PLGA particles on the surface of the core particles, resulting in the formation of coating films on dispersed particles of SiO₂ and agglomerates of TiO₂. The influences of the core particle size, spray nozzle diameter as well as powder-to-polymer weight ratio were also investigated and discussed with respect to the coating performance.     

微胶囊红磷膨胀型阻燃剂的制备及应用

制备了微胶囊红磷/季戊四醇/三聚氰胺膨胀型阻燃剂(IFR)。采用吸湿性、抗氧化性、SEM、TG等测试方法对阻燃剂进行了表征。结果表明:微胶囊红磷的吸湿性减小、抗氧化性增强;TG分析显示,微胶囊红磷在385~422℃、470~553℃有两个失重阶段;600℃时,未包覆红磷残重仅为6%,而微胶囊包覆红磷的残重为12%;微胶囊红磷膨胀型阻燃剂的最佳组成为:微胶囊红磷:季戊四醇:三聚氰胺=4.00:0.75:2.00(摩尔比);500℃下,IFR残重高达65.06%;当IFR添加量为30%时,阻燃环氧树脂的氧指数从未添加IFR时的19.0%提高到26.3%。     

Micronization of drug particles via RESS process

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 vapour pressure solutes. The RESS containing a nonvolatile solute leads to the loss of solvent power by the fast expansion of the supercritical solution through an adequate nozzle, which can cause solute precipitation. The nozzle configuration plays an important role in RESS method and has a great effect on the size and morphology of the precipitated particles. In this study, ibuprofen was used as a simple test. In addition, besides the nozzle configuration, the effect of other parameters including extraction pressure (140-220 bar), extraction temperature (313-333 K), spraying distance (1-10 cm) and pre-expansion temperature (363-423 K) was investigated on the size and morphology of the precipitated particles of mefenamic acid. The SEM images also show that the precipitated particles of ibuprofen and mefenamic acid had a slight modification in morphology.     

Supercritical CO2 Spray Drying of Ethyl Cellulose (EC) for Preparing Microparticles

Even though common spray drying has been widely used for drying food and related products, the effect of drying conditions of supercritical CO₂ spray drying on the particle sizes of dried products has not been well studied. The objective of this study was to study the effect of drying conditions and design parameters on the particle sizes of biomaterials dried with supercritical CO₂ spray drying. The ethyl cellulose (EC) microparticles were prepared with supercritical CO₂ as the dry medium using an experimental spray-drying apparatus. This research studied the influences of spray nozzle diameter, mass ratio of gas to liquid, solution concentration, temperature, and pressure on the physical characteristics of ethyl cellulose microparticles. The results indicated that the average size of the dried particles ranged from 1.07 to 9.84 µm. The spray nozzle with 8-mm diameter produced smaller microparticles with narrower distribution than the 4-mm spray nozzle. The average particle size increased with the increase of the ratio of gas to liquid. Also, the average size and distribution of the microparticles increased with the rise of temperature and solution concentration but decreased with the increase of pressure.     

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).     

Optimization of the Extraction of <Emphasis Type="Italic">Alpinia oxyphylla</Emphasis> Essence Oil in Supercritical Carbon Dioxide

The essence oil of the Alpinia oxyphylla seed has been used as a vasodilatatory and analgesic agent in pharmacology. The extraction of the essence oil in supercritical carbon dioxide (SC-CO₂) from Alpinia oxyphylla seeds was investigated. Small particles were obtained after breaking open, sieving, and drying from the Alpinia oxyphylla seeds. The small particles were placed in a 5-L extraction tank in a temperature-controlled system. The CO₂ flow rate of the system was set at 1 L/min in this study. Response surface methodology with a three-factor and three-level Box-Behnken experimental design was used to evaluate the effects of the reaction parameters such as extraction time (1, 2, 3 h), temperature (45, 55, 65 °C), and pressure (20, 30, 40 MPa), on the extraction yield of the essence oil from Alpinia oxyphylla seeds. The results indicate that the extraction pressure was the most important parameter affecting the yield of the essence oil. A model for the estimation of the yield was developed. Based on the analysis of ridge max, the optimal extraction conditions were established as an extraction time of 2.8 h, a temperature of 67.5 °C, and a pressure of 28.5 MPa, with an expected yield of 2.78%. Extraction of Alpinia oxyphylla essence oil in SC-CO₂ under these optimal conditions was conducted, and a yield of 2.77 ± 0.19% was obtained.     

Effects of extraction temperature, extraction pressure and nozzle diameter on micronization of cholesterol by RESS process

Micronized cholesterol particles were produced via the Rapid Expansion of Supercritical CO₂ Solutions (RESS) process. Taguchi design was used for designing the experimental plan to investigate the effects of three parameters including extraction temperature (40-60 °C), extraction pressure (100-160 bar) and nozzle diameter (0.15-0.24 mm) on the size and morphology of the cholesterol particles produced by the RESS process. The characterization of the particles was carried out using scanning electron microscopy (SEM) and X-ray diffraction (XRD) measurements to evaluate the performance of RESS process. The average particle size of the original material was 55 μm ± (2.84) while the average particle size of cholesterol after size reduction via the RESS process was between the minimum of 0.62 μm ± (0.03) and the maximum of 4.83 μm ± (0.18) depending upon the experimental conditions used. It was observed that both increasing the temperature from 40 to 60 °C and increasing the nozzle diameter from 0.15 to 0.24 mm result a reducing effect on the average particle size, whereas extraction pressure (100-160 bar) change has slight effect on the average particle size.     

A rapid microwave-assisted method of synthesizing wurtzite Cu2ZnSnS4 in a novel solvent and its controlled phase evolution

Stable pure wurtzite Cu₂ZnSnS₄ (CZTS) microparticles are successfully synthesized and the phase control evolution is studied, where a mixture of ethylene glycol (EG) and triethylenetetramine (TETA) is used in conjunction with a rapid and low-cost microwave-assisted method to control the crystalline phases of the particles. The CZTS phase is mainly controlled by changing the reaction time, reaction power, surfactant vs. raw material ratio. The particles are characterized with X-ray diffraction, Raman spectroscopy, scanning electron microscope, transmission electron microscope and UV–vis spectrophotometer. The results show that when EG and TETA are mixed in a ratio of 1:6 and the reaction power is 800 W, CZTS in pure wurtzite phase is obtained rapidly when the raw material ratio is Cu: Zn: Sn: S = 2 : 1.25: 1: 6 and the reaction time is 120 s. The phase transition can be effectively controlled by controlling the reaction conditions such as raw material ratio, reaction power and reaction time.     

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.     

Concentration of Natural Vitamin E Using a Continuous Countercurrent Supercritical CO2 Extraction‐Distillation Dual Column

A continuous countercurrent supercritical CO₂ extraction‐distillation dual‐column process was developed to extract and concentrate natural vitamin E (VE) from soybean oil deodorizer distillate (SODD). The experimental results demonstrated that process parameters such as extraction pressure, temperature, and solvent‐to‐feed ratio significantly impacted on the extraction efficiency of natural VE. A new five‐parameter mass transfer model for the continuous countercurrent supercritical CO₂ extraction‐distillation dual‐column process was presented based on the Penetration and Double‐Film theories. The calculated values of the mathematical model agreed well with the experimental data, with absolute average relative deviation values of less than 25 %.     

Technical optimization of the extraction of andrographolide by supercritical CO2

An experimental design has been built in order to study the influence of different parameters on the crystallization ratio and purity of andrographolide extraction using supercritical CO₂: pressure (8–24 MPa), temperature (40–70 °C) and extraction duration (45–105 min). Crystallization ratios are between 14.32 and 72.29 wt%, and purities are between 43.11 and 79.78 wt%, indicating that the experimental design covers a large range of results. The results indicate that pressure and extraction duration are the most influencing parameters.     

Micronization and characterization of squid lecithin/polyethylene glycol composite using particles from gas saturated solutions (PGSS) process

Lecithin was isolated from squid viscera residues after supercritical carbon dioxide (SC-CO₂) extraction at 25 MPa and 45 °C. The particle formation of squid lecithin with biodegradable polymer, polyethylene glycol (PEG) was performed by PGSS using SC-CO₂ in a thermostatted stirred vessel. By applying different temperatures (40 and 50 °C) and pressures (20–30 MPa), conditions were optimized. Two nozzles of different diameters (250 and 300 μm) were used for PGSS and the reaction time was 1 h. The average diameter of the particles obtained by PGSS at different conditions was about 0.74–1.62 μm. The lowest average size of lecithin particle with PEG was found by the highest SC-CO₂ density conditions with the stirring speed of 400 rpm and nozzle size of 250 μm. The inclusion of lecithin in PEG was quantified by HPLC. Acid value and peroxide value was measured after micronization of lecithin.