Supercritical Fluid Processing Research Articles

A superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes with improved solubility and dissolution: Supercritical fluid process

Advantages of the supercritical fluid (SCF) process compared to the conventional solution stirring method (CSSM) in the preparation of daidzein-hydroxypropyl-β-cyclodextrin (HPβCD) complexes were investigated. Formation of daidzein/ HPβCD inclusion complexes was confirmed by Fourier transformed-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Particle size, inclusion yield, drug solubility and dissolution of daidzein/HPβCD complexes were evaluated. Compared to CSSM, the SCF process resulted in higher inclusion yield and higher solubility. Also, extended dissolution of daidzein from the SCF processed HPβCD inclusion complexes was observed, with only 22.94 % released in 45 min, compared to its rapid release from those prepared by CSSM, with 98.25 % drug release in 15 min. This extended release of daidzein from SCF prepared inclusion complexes was necessary to avoid drug precipitation and improve drug solubilisation in the gastrointestinal tract. The results showed that the SCF process is a superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes.

Cefquinome Controlled Size Submicron Particles Precipitation by SEDS Process Using Annular Gap Nozzle

An annular gap nozzle was applied in solution enhanced dispersion by supercritical fluids (SEDS) process to prepare cefquinome controlled size submicron particles so as to enhance their efficacy. Analysis results of orthogonal experiments indicated that the concentration of solution was the primary factor to affect particle sizes in SEDS process, and feeding speed of solution, precipitation pressure, and precipitation temperature ranked second to fourth. Meanwhile, the optimal operating conditions were that solution concentration was 100 mg/mL, feeding speed was 9 mL/min, precipitation pressure was 10 MPa, and precipitation temperature was 316 K. The confirmatory experiment showed that D50 of processed cefquinome particles in optimal operating conditions was 0.73 μm. Moreover, univariate effect analysis showed that the cefquinome particle size increased with the increase of concentration of the solution or precipitation pressure but decreased with the increase of solution feeding speed. When precipitation temperature increased, the cefquinome particle size showed highest point. Moreover, characterization of processed cefquinome particles was analyzed by SEM, FT-IR, and XRD. Analysis results indicated that the surface appearance of processed cefquinome particles was flakes. The chemical structure of processed cefquinome particles was not changed, and the crystallinity of processed cefquinome particles was a little lower than that of raw cefquinome particles.

Anchoring of ultrafine Co3O4 nanoparticles on MWCNTs using supercritical fluid processing and its performance evaluation towards electrocatalytic oxygen reduction reaction

Anchoring ultrafine Co3O4 nanoparticles on MWCNTs using a supercritical fluid showed high ORR performance.

Supercritical fluid processing for the synthesis of NiS2 nanostructures as efficient electrocatalysts for electrochemical oxygen evolution reactions

A facile supercritical fluid process was demonstrated for the synthesis of cubic NiS2 nanostructures for efficient electrochemical oxygen evolution reactions.

Cytochrome c Stabilization and Immobilization in Aerogels.

Sol-gel-derived aerogels are three-dimensional, nanoscale materials that combine large surface area with high porosity. These traits make them useful for any rate-critical chemical process, particularly sensing or electrochemical applications, once physical or chemical moieties are incorporated into the gels to add their functionality to the ultraporous scaffold. Incorporating biomolecules into aerogels, other than such rugged species as lipases or cellulose, has been challenging due to the inability of most biomolecules to remain structurally intact within the gels during the necessary supercritical fluid (SCF) processing. However, the heme protein cytochrome c (cyt.c) forms self-organized superstructures around gold (or silver) nanoparticles in buffer that can be encapsulated into wet gels as the sol undergoes gelation. The guest-host wet gel can then be processed to form composite aerogels in which cyt.c retains its characteristic visible absorption. The gold (or silver) nanoparticle-nucleated superstructures protect the majority of the protein from the harsh physicochemical conditions necessary to form an aerogel. The Au~cyt.c superstructures exhibit rapid gas-phase recognition of nitric oxide (NO) within the bioaerogel matrix, as facilitated by the high-quality pore structure of the aerogel, while remaining viable for weeks at room temperature. More recently, careful control of synthetic parameters (e.g., buffer concentration, protein concentration, SCF extraction rate) have allowed for the preparation of cyt.c-silica aerogels, sans nucleating nanoparticles; these bioaerogels also exhibit rapid gas-phase sensing while retaining protein structural stability.

Controlling the Shape of LiMPO4 and Li2MSiO4 By Supercritical Fluid for High Energy Density Li-Ion Battery

LiMPO4 and Li2MSiO4 (M = Fe, Mn, Co, Ni) cathode materials holds promise for next-generation of lithium-ion batteries and future application in as hybrid electric vehicles or electric vehicles. In lithium intercalation compounds, the lithium diffusion along the channel is highly anisotropic which strongly depends on size and shape of the materials. Thus, controlling size and shape of cathode materials are crucial to improve the lithium intercalation rate and improve power density of the batteries. Here, we report a rapid, one-pot Supercritical Fluid process for the preparation of size, and morphology controlled LiMPO4 and Li2MSiO4 (M: Fe, Mn, Co, Ni) nanocrystals (Fig. 1) [1]. Various organic additives have been used to tailor the size, shape as well as surface functionality of the nanocrystals. Nanoparticles, nanoplates and their assembly into superlattices and microspheres has been obtained by SCFs. The effect of the nanocrystal morphology on the cathode performance was investigated in detail. Fig. 1. TEM image of LiFePO4 nanosheets synthesized by supercritical fluid processing and schematic illustration of enhanced electrochemical performance. [1] Q. D. Truong, M. K. Devaraju, T. Tomai and I. Honma, ACS Appl. Mater. Interfaces, 2013, 5 (20), 9926−9932; M. K. Devaraju, Q. D. Truong and I. Honma, RSC Adv., 2013, 3, 20633-20638; Q. D. Truong, M. K. Devaraju, Y. Ganbe, A. Tomai, I. Honma, Scientific Reports , 2014, 4, 3975; Q. D. Truong, M. K. Devaraju, Y. Sasaki, H. Hyodo, T. Tomai, I. Honma, C hemistry of Materials , 2014, 26 (9), 2770−2773; M. K. Devaraju, Q. D. Truong, T. Tomai, I. Honma, RSC Advances , 2014, 4 (52), 27452-27470; M. K. Devaraju, I. Honma, Jou rnal of Materials Chemistry A, 2014, 2 (41), 17400-17407. Q. D. Truong, M. K. Devaraju, Y. Sasaki, H. Hyodo, I. Honma, Chemistry - A European Journal , 2014, 20 (49), 16210-16215. Figure 1

State of the art of nanocrystals technology for delivery of poorly soluble drugs

Formulation of nanocrystals is a distinctive approach which can effectively improve the delivery of poorly water-soluble drugs, thus enticing the development of the nanocrystals technology. The characteristics of nanocrystals resulted in an exceptional drug delivery conductance, including saturation solubility, dissolution velocity, adhesiveness, and affinity. Nanocrystals were treated as versatile pharmaceuticals that could be delivered through almost all routes of administration. In the current review, oral, pulmonary, and intravenous routes of administration were presented. Also, the targeting of drug nanocrystals, as well as issues of efficacy and safety, were also discussed. Several methods were applied for nanocrystals production including top-down production strategy (media milling, high-pressure homogenization), bottom-up production strategy (antisolvent precipitation, supercritical fluid process, and precipitation by removal of solvent), and the combination approaches. Moreover, this review also described the evaluation and characterization of the drug nanocrystals and summarized the current commercial pharmaceutical products utilizing nanocrystals technology.

Supercritical Fluid Facilitated Disintegration of Hexagonal Boron Nitride Nanosheets to Quantum Dots and Its Application in Cells Imaging

Preparation of quantum dots (QDs) and exfoliation of two-dimensional layered materials have gathered significant attention in recent days. Though, there are number of attempts have been reported, facile and efficient methodology is yet to be explored. Here, we demonstrate supercritical fluid processing approach for rapid and facile synthesis of blue luminescent BN QDs from layered bulk material via in situ exfoliation followed by disintegration. The microscopic and AFM analysis confirmed the few layer BN QDs formation. The strong luminescent behavior of BN QDs is utilized to stain Gram-negative bacterial cells specifically in the presence of Gram-positive bacterial cells.

Fabrication of three-dimensional CuInS2 solar-cell structure via supercritical fluid processing

In this study, we fabricated a three-dimensional CuInS2 solar-cell structure using supercritical fluid deposition and sulfurization, in which p-n junction is formed at the large surface of a nanoporous n-type TiO2 film filled with a p-type CuInS2 semiconductor to facilitate the efficient collection of photoinduced electrons and holes. Using the reductive reaction of organometallic precursors dissolved in supercritical fluid at the surface, we successfully and efficiently deposited Cu–In film inside the nanoporous film consisting of TiO2 nanoparticles with a diameter of a few tens of nanometers. The CuInS2 film formed following the sulfurization of the Cu–In film exhibited an ideal band gap (1.5eV) and photoconductivity. The results obtained in this study expand the applicability of supercritical fluid technology to the fabrication of chalcogenide semiconductors inside nanostructured materials and will contribute to the future development of or improvement in various types of energy devices.

Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process

The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen–methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11±0.09% dissolving at the end of 60min, while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200bar released 99.39±2.34% of the drug at the end of 30min. All the binary mixtures processed by supercritical carbon dioxide at 45°C exhibited a drug release of more than 80% within the first 10min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.

The use of supercritical anti-solvent (SAS) technique for preparation of Irbesartan-Pluronic® F-127 nanoparticles to improve the drug dissolution

Irbesartan (IRB) is used in the management of hypertension. IRB is a poorly water-soluble drug with very low aqueous solubility. This drug has poor bioavailability after oral administration. This study aimed at improving the dissolution of IRB through the preparation of solid dispersions (SDs) using supercritical fluid based on supercritical anti-solvent (SAS) technique. Solid dispersions of IRB were prepared by a surfactant named Pluronic® F-127 (briefly pluronic) at a ratio of 1:1. The physical mixtures were provided as controls. Drug solubility of samples was studied based on saturation solubility and the in vitro dissolution rate of the drug was investigated. The SAS formulation was characterized by UV–Vis, SEM, PXRD, DSC and FTIR. The dissolution rate and solubility of IRB improved remarkably with a non-ionic surfactant using SAS-based technique. SAS processes showed signs of less crystallinity of the drug due to the transformation of its crystalline state into the amorphous state. The analysis of dissolution data indicated that enhanced drug dissolution can be achieved where the SDs in the supercritical fluid process consisted of pluronic nanoparticles. Finally, the SAS-SD formulation showed an increase in relative bioavailability than the pure IRB.

A Supercritical Fluid-Based Process for the Production of Fluorescein-Loaded Liposomes

Fluorescein is a synthetic dye used as a marker to monitor the absorption of liposomes into tissues, but its efficient entrapment is still challenging. In this work, we apply a supercritical fluid process that allows the production of liposomes with a high drug encapsulation efficiency. The effects of operating parameters such as the diameter of the injector, the concentration of phospholipids, and the concentration of fluorescein were studied. Liposomes with mean diameters down to ∼300 nm were obtained with fluorescein encapsulation efficiencies of ≤96%. In detail, the increase in the concentration of phospholipids produced a relative increase in liposome mean diameter and particle size distribution width. With an increase in fluorescein theoretical loading, instead, a reduction in liposome mean diameters and standard deviation was obtained. Smaller liposomes were produced using smaller injector diameters; however, the reduction of the injector diameter from 80 to 40 μm caused a reduction in the fluoresc...

Synthesis of lithium titanium oxide (Li4Ti5O12) with ultrathin carbon layer using supercritical fluids for anode materials in lithium batteries

Lithium titanium oxide (LTO: Li4Ti5O12) particles were produced via a continuous supercritical fluid process for use as anodes in lithium ion batteries. The synthesized LTO particles in supercritical water (scH2O) or in supercritical methanol (scMeOH) generate nanoparticles of 10–30 nm sizes, and the modified LTO particles using oleylamine in scMeOH affects the inhibition of particle growth. The modified LTO particle was coated by the usage of supercritical carbon dioxide (scCO2) and polyethylene glycol (PEG-400). The conformal coverage of the carbon layer on LTO particles with a thickness of 1.2 nm, and a uniform distribution of carbon on the entire surface of LTO particles are confirmed. The modified and carbon-coated LTO with a carbon content of 5.3 wt% exhibits a high discharge capacity of 175 mAh/g (which approaches the theoretical value of LTO) at 0.1 C and 83 mAh/g at 50 C. The carbon-coated LTO prepared using supercritical fluids delivered 160, 153, 123 mAh/g at 1 C and 60 °C, room temperature, and −25 °C, respectively.

High performance supercapacitor using N-doped graphene prepared via supercritical fluid processing with an oxime nitrogen source

Heteroatom doped graphene has been proved for its promising applications in electrochemical energy storage systems. Here, nitrogen (N) doped graphene was prepared via two different techniques namely supercritical fluid assisted processing and hydrothermal heat treatment using dimethylglyoxime (DMG) as an oxime nitrogen precursor. The FT-IR and Raman spectra showed the N-containing functional group in the graphene. The XRD analysis revealed the complete reduction of graphene oxide during the supercritical fluid processing. The elemental analysis and X-ray photoelectron spectroscopy revealed the amount and nature of N-doping in the graphene, respectively. The surface morphology and physical nature of the samples were analyzed using scanning and transmission electron microscopic analysis. The electrochemical performance of prepared electrode materials was evaluated using cyclic voltammetry, galvanostatic charge-discharge analysis and electrochemical impedance spectroscopy. The N-doped graphene prepared via supercritical fluid assisted processing exhibit enhanced capacitive behaviour with a maximum specific capacitance of 286Fg−1 at a current density of 0.5A/g. The cycling studies showed 98% specific capacity retention with 100% coulombic efficiency over 1000 cycles at 5A/g. The enhanced specific capacitance of N-doped graphene prepared via supercritical fluid heat treatment over the hydrothermal heat treatment is ascribed to the nature of N-doping in the graphene.

Application of supercritical fluid processes

The present work deals with the storage of Hydrogen where promising ways are based on the solubility of organic or inorganic compounds in supercritical fluids, inducing specific interactions to retain this non polluting energy vector.Consequently the modeling of the solubility of polar organic compounds like Ortho Hydroxy benzoic acid (o-HBA), and Para Hydroxy benzoic acid (p-HBA), Dichloro diphenyl Trichloro ethane (DDT) and 2,4-Dichloro phenoxyacetic acid (usually referred to by its abbreviation, (2,4-D) as well as their mixtures, in supercritical fluids such as carbon dioxide, is presented.For the two binary systems i.e. o-HBA-CO2, DDT-CO2 the model combining the cubic Redlich Kwong (RK) equation of state (EOS) with the van der Walls (VW) mixing rule (MR) at constant temperature of 313 K and a pressure range of 120–220bar, showed quite good results compared to the experimental values. However the model Redlich–Kwong–Soave (RKS)–Wong–Sandler (WS) provided a better correlation.Similarly the model RK-WS gave better results for the solubility of o-HBA in CO2 and for the mixture o-HBA–2,4-D in CO2.The obtained solubilities of p-HBA in supercritical carbon dioxide were found to be higher than that of o-HBA. This can be explained by the differences in the intermolecular interactions which are relatively weak for the case of o-HBA.The results obtained from the combinations Patel–Teja (PT)-VW and PT-WS showed important deviations compared to the experimental values and this for all the considered systems.

Supercritical fluid processing applications in biomaterials

Event Abstract Back to Event Supercritical fluid processing applications in biomaterials Michael Favaloro1, Hans Schonemann2 and Val Krukonis2 1 CompositeTechs, LLC, United States 2 Phasex, United States Introduction: The Supercritical Fluid (SCF) Process has been used as an enabling technology in the processing of biomaterials. Significant success has been achieved in the utilization of this process; however, the lack of understanding and knowledge of the technology has prevented increased usage. This paper describes the process in detail, provides advantages and disadvantages of the process as well as examples of existing applications, and discusses possible areas of further exploitation in the biomaterials community. Materials and Methods: An SCF is any substance above its critical point, i.e., above the temperature and pressure where distinct liquid and gas phases do not exist. It is a super-solvent, in that it can effuse through solid materials like a gas, and it can dissolve materials like a liquid. [1] SCF's are used in biomaterials for many applications. When compared to solvent extraction, supercritical fluids leave no trace solvents. Solvent residues and contaminants can be removed from polymers and high molecular weight oils. SCF's can separate, or fractionate organic materials into narrow bands of molecular weight, in some cases better than the molecular distillation process. Reactive monomers and molded implants can be purified. Materials can be dissolved and recrystallized into narrow particle size distributions. Similarly, organic materials can be dissolved and infused into microporous solids at low temperature, eliminating risk of thermal degradation.[3] Results and Discussion: Management of SCF's allows one to tailor a process for a variety of organic materials and applications, as shown in the following examples: SCF's can fractionate some polymers and chemicals that are unable to be separated even by molecular distillation. Some applications, such as medical implants, require extremely high levels of purification which are possible with SCF but not with conventional methods. The high temperatures required to increase vapor pressure of the monomers would result in degradation of the polymers, or, in some cases, the polymerization process would be affected. . Similar purification processing is in production for silk-like orthopedic structures used in medical implant applications. In the particle formation process, an organic material is ‘dissolved’ in the SCFand transferred to a chamber with lower pressure. The material precipitates, or recrystallizes, out of solution, and particle size is controlled. One example is with Beta- estradiol, a medical grade organic material. A fine, uniform particle size was achieved by recrystallization.[4] SCF's with dissolved polymers or organic constituents can be used to infiltrate microporous solids, and by reduction of pressure, the dissolved constituents that come out of solution remain within the solid.This process can be utilized to incorporate antibiotics and immunosuppressant or other anti-reject drugs into implants. The drugs could be utilized to reduce the risk of rejection of the implant by the body, or to provide a long term, slowly diffused antibiotic. Conclusion: SCF processing offers significant value to biomaterials engineers as a novel tool. . The process can be used to extract monomers and contaminants, purify raw materials and molded parts, manage particle size distribution, and infiltrate microporous components. Applications have been demonstrated and production is ongoing for medical implants.

Rapid, one-pot synthesis of luminescent MoS2nanoscrolls using supercritical fluid processing

A rapid, one-pot synthesis of surfactant-free MoS2nanoscrolls by supercritical fluid processing is demonstrated. The MoS2nanoscrolls showed size dependent luminescence behaviour. This method is promising for the direct exfoliation of other 2D layered materials.

Production and stabilization of olanzapine nanoparticles by rapid expansion of supercritical solutions (RESS)

The purpose of the work was the production, stabilization and characterization of olanzapine (OLZ) nanoparticles by the RESS and RESSAS processes. A pilot scale unit for supercritical fluid processing was used for the production of RESS OLZ nanoparticles and RESSAS nanosuspensions. Supercritical OLZ-solution (scCO2, 20MPa/50°C) was expanded into air (RESS) or into an aqueous solution (HPMC, PEG, PEG+SLS, or polysorbate 80, RESSAS). Nanosuspensions were characterized for particle size, PSD and zetapotential. The freeze-dried nanoparticles were further evaluated for FTIR and OLZ dissolution rate. RESS OLZ could be produced with a mean particle size of 191.4±9.6nm, i.e., a 200-fold size reduction compared to the original anhydrous material. The material was partially amorphous, as confirmed by DSC and FTIR. The particle size of RESSAS OLZ nanosuspensions was in the same range. The highest stability (size and solid-phase) of nanosuspensions before and after freeze-drying was achieved when PEG+SLS were considered. In conclusion, the preparation of OLZ nanoparticles with improved dissolution rate and known solid-state forms was achieved by RESS and RESSAS processes.

One pot synthesis of in situ Au decorated LiNiPO4 nanoplates for Li-ion batteries

In this work, we report in situ Au decoration on the surface of the LiNiPO4 nanoplates via supercritical fluid process for the first time. The purpose of the in situ Au nanoparticles decoration was to improve electrochemical performance by improving the surface electrical conductivity. X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS) and elemental mapping was adopted to confirm the Au nanoparticles deposition on the LiNiPO4 nanoplates. The discharge capacity of 66mAhg−1 with a flat profile at above 4.5V was observed, which is better than that of acetylene black (AB) and commercial Au particles mixed LiNiPO4 nanoplates.

Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties

The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of olanzapine-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of olanzapine. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analysed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of olanzapine with methyl-β-cyclodextrin. All the binary mixtures of olanzapine with methyl-β-cyclodextrin, except physical mixture, exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. The characterisation by different analytical techniques suggests complete complexation or amorphisation of olanzapine and methyl-β-cyclodextrin complexes prepared by supercritical carbon dioxide processing method. Therefore, organic solvent-free supercritical carbon dioxide processing method proved to be novel and efficient for the preparation of solid inclusion complexes of olanzapine with methyl-β-cyclodextrin. The preliminary data also suggests that the complexes of olanzapine with methyl-β-cyclodextrin will lead to better therapeutic efficacy due to better solubility and dissolution properties.