Supercritical Solutions Research Articles

Determining the Solubility of Nifedipine and Quinine in Supercritical Fluid Carbon Dioxide Using Continuously Stirred Static Solubility Apparatus Interfaced with Online Supercritical Fluid Chromatography

A high pressure vessel equipped with continuous magnetic stirring has been interfaced directly online with supercritical fluid chromatography (SFC). The interface consists of an oven housing a recirculation pump that maintains a constant flow of supercritical fluid solution from the vessel through a sample injection valve for online SFC analysis. The method involves increasing the vessel pressure in controlled steps to produce a series of progressively more saturated supercritical fluid carbon dioxide solutions for online SFC solubility measurements. The integrated static solubility system provides a convenient means to ensure equilibrium is established prior to performing online SFC solubility measurements and also facilitates a self-validation accuracy check procedure. For nifedipine, solubility data was obtained at 333.15 and 353.15 K through the pressure range from 12.5 to 27.5 MPa using 2.5 MPa steps. For quinine, solubility data was obtained at 323.15 and 343.15 K through the pressure range from 12....

Birch Bark Dry Extract by Supercritical Fluid Technology: Extract Characterisation and Use for Stabilisation of Semisolid Systems

Triterpene compounds like betulin, betulinic acid, erythrodiol, oleanolic acid and lupeol are known for many pharmacological effects. All these substances are found in the outer bark of birch. Apart from its pharmacological effects, birch bark extract can be used to stabilise semisolid systems. Normally, birch bark extract is produced for this purpose by extraction with organic solvents. Employing supercritical fluid technology, our aim was to develop a birch bark dry extract suitable for stabilisation of lipophilic gels with improved properties while avoiding the use of toxic solvents. With supercritical carbon dioxide, three different particle formation methods from supercritical solutions have been tested. First, particle deposition was performed from a supercritical solution in an expansion chamber. Second, the Rapid Expansion of Supercritical Solutions (RESS) method was used for particle generation. Third, a modified RESS-procedure, forming the particles directly into the thereby gelated liquid, was developed. All three methods gave yields from 1% to 5.8%, depending on the techniques employed. The triterpene composition of the three extracts was comparable: all three gave more stable oleogels compared to the use of an extract obtained by organic solvent extraction. Characterizing the rheological behaviour of these gels, a faster gelling effect was seen together with a lower concentration of the extract required for the gel formation with the supercritical fluid (SCF)-extracts. This confirms the superiority of the supercritical fluid produced extracts with regard to the oleogel forming properties.

Microencapsulation and characterization of liposomal vesicles using a supercritical fluid process coupled with vacuum-driven cargo loading

A new technique of liposomal microencapsulation, consisting of supercritical fluid extraction followed by rapid expansion of the supercritical solution and vacuum-driven cargo loading, was successfully developed. It is a continuous flow-through process without usage of any toxic organic solvent. For use as a coating material, the solubility of soy phospholipids in supercritical carbon dioxide was first determined using a dynamic equilibrium system and the data was correlated with the Chrastil model with good agreement. Liposomes were made with D-(+)-glucose as a cargo and their properties were characterized as functions of expansion pressure, temperature, and cargo loading rates. The highest encapsulation efficiency attained was 31.7% at the middle expansion pressure of 12.41MPa, highest expansion temperature of 90°C, and lowest cargo loading rate of 0.25mL/s. The large unilamellar vesicles and multivesicular vesicles were observed to be a majority of the liposomes produced using this eco-friendly process.

Nucleation of Pharmaceuticals Crystalline Phase from Supercritical Fluid Solution. The Conformational Equilibriums Impact on Polymorphic Modifications*

Nucleation of Pharmaceuticals Crystalline Phase from Supercritical Fluid Solution. The Conformational Equilibriums Impact on Polymorphic Modifications*

Finite bandwidth, nonlinear convective flow in a mushy layer

Finite amplitude convection with a continuous finite bandwidth of modes in a horizontal mushy layer during the solidification of binary alloys is investigated. We analyze the nonlinear convection for values of the Rayleigh number close to its critical value by using multiple scales and perturbation techniques. Applying a combined temporal and spatial evolution approach, we determine a set of three coupled differential equations for the amplitude functions of the convective modes. A large number of new subcritical or supercritical stable solutions to these equations in the form of steady rolls and hexagons with different horizontal length scales are detected. We find, in particular, that depending on the parameter values and on the magnitude and direction of the wave number vectors for the amplitude functions, hexagons with down-flow or up-flow at the cells’ centers or rolls can be stable. Rolls or hexagons with longer horizontal wave length can be stable at higher amplitudes, and there are cases where hexagons are unstable for any value of the Rayleigh number, while rolls are stable only for the values of the Rayleigh number beyond some value. We also detected new stable and irregular flow patterns with two different horizontal scales in the form of superposition of either two sets of hexagons or two sets of inclined rolls.

Fluctuational parameters based on the Bhatia–Thornton theory for supercritical solutions: Application to a supercritical aqueous solution of n-pentane

To study the structural fluctuation of supercritical solutions, we introduced three fluctuational parameters, a scattering factor, a density factor and a volume factor, which were based on the Bhatia–Thornton theory. In the present study, the density dependence of the structural inhomogeneity in a supercritical aqueous solution of n-pentane was discussed using the scattering factor and the density factor obtained from small-angle X-ray scattering and the fluid density measurements, respectively. Although both these factors have their maxima at the same density position in the case of neat supercritical fluids, a significant difference between the two factors is observed in the binary solution. The large difference occurs by the contribution of the concentration fluctuation in the system. Based on the difference between the factors, it is suggested that a phase separation of the system exists in the higher-fluid-density region.

Experimental investigation for the solubility and micronization of pyridin-4-amine in supercritical carbon dioxide

Novel solute solubility data of pyridin-4-amine (C5H6N2, also known as 4-aminopyridine or fampridine) in supercritical carbon dioxide are measured in this study. This compound is an active pharmaceutical ingredient (API) for the treatment of neurological disorder, and the Alzheimer’s disease. The solubility data at three isotherms (308.2, 318.2 and 328.2K) are reported for pressures from 10 to 22MPa. These solubility results are ranged from 2×10−5 to 2×10−4mol fraction, and are confirmed as thermodynamically consistent. We further apply the rapid expansion of supercritical solution (RESS) process to micronize this API. At our optimal operation condition, the original API with a mean particle size of 532.3±236.5μm is micronized to 0.32±0.07μm. The RESS processed products are much more uniform and nearly spherical amorphous particles. Finally, an in vitro dissolution test illustrates an enhanced dissolution rate by 2.9 times for the micronized pyridin-4-amine.

Phase equilibrium and micronization for flufenamic acid with supercritical carbon dioxide

Abstract The solubility data of flufenamic acid (FFA, a fluorinated and non-steroidal anti-inflammatory drug) in supercritical carbon dioxide were measured with a semi-flow type phase equilibrium apparatus at temperatures from 313.2 K to 333.2 K and pressures up to 21 MPa. Over the experimental conditions, the solubility values are between 0.8 × 10−6 and 2.13 × 10−4 in mole fraction. These solid–gas equilibrium data were correlated with the Chrastil model, Mendez-Santiago and Teja model, and the Peng–Robinson equation of state to average absolute relative deviations of 11.4%, 21.1%, and 7.8%, respectively. Since the solubility of FFA can be as high as 10−4, rapid expansion of supercritical solution (RESS) method is favorable for preparing ultra-fine FFA particles. The experimental results of the RESS micronization show that extraction pressure, pre-expansion temperature, and dimension of capillary tube are the key factors to govern the morphology and the mean size of the resultant particles. While sticky agglomerates were obtained from lower extraction pressures with larger and/or longer capillary tube, needle-like particles were produced at higher extraction pressures with smaller and/or shorter capillary tube. Moreover, operating at lower pre-expansion temperatures and higher crystallization temperatures yielded longer and thinner needle-like crystals. Under higher extraction pressure (e.g., 21 MPa), the mean size of the generated FFA particles distributed from 0.5 to 5.1 µm and from 0.1 to 1.1 µm for the lengths of major and minor axes, respectively. It is also found that the particulate FFA converts from original form I into form III after the RESS processing.

Symmetry and decay of traveling wave solutions to the Whitham equation

This paper is concerned with decay and symmetry properties of solitary-wave solutions to a nonlocal shallow-water wave model. An exponential decay result for supercritical solitary-wave solutions is given. Moreover, it is shown that all such solitary-wave solutions are symmetric and monotone on either side of the crest. The proof is based on the method of moving planes. Furthermore, a close relation between symmetric and traveling-wave solutions is established.

The effect of CO2 and N2 on phase relations, fluid composition, and quartz solubility in amphibolite facies metamorphic rocks

Phase equilibria in the system SiO2–TiO2–Al2O3–Fe2O3–MnO–MgO–CaO–Na2O–K2O–P2O5–H2O–CO2–N2 are calculated to illustrate phase relations in amphibolite facies metasediments over a wide range of X[H2O–CO2–N2] conditions at 600 °C and 4.4 kb. Calculations are performed using the Gibbs free energy minimization technique. Results are presented in plots showing stable mineral assemblages as a function of total carbon in the system at varying water (\(a_{{{\text{H}}_{2} {\text{O}}}}\) = 1) content in the presence/absence of N2 in the fluid. The calculations indicate that the typical assemblage plagioclase—quartz—biotite—ilmenite—garnet—apatite is restricted to the rocks with CO2 saturation and \(X_{{{\text{H}}_{ 2} {\text{O}}}}\) higher than 60% in the fluid. Significant decrease in \(X_{{{\text{CO}}_{2} }}\) favors the stability of muscovite rather than garnet, whereas the decrease in \(X_{{{\text{H}}_{ 2} {\text{O}}}}\) leads to the stability of microcline over all range of \(X_{{{\text{CO}}_{2} }}\). This paper also presents the composition and parameters (pH, Eh) of the fluid equilibrated with mineral assemblage. It is shown that the presence of low concentrations of N2 causes the fluid to consist of two phases when an aqueous supercritical solution (AS) coexists with a supercritical fluid with gas-like properties (SF). At high concentration of N2, the fluid consists of SF alone; in the absence of nitrogen, the fluid consists of AS alone. The solubility of monomer SiO20 and dimer Si2O40 decreases with increasing CO2 and after CO2 saturation point is held constant. The magnitude of the silica solubility at CO2 saturation depends upon the water content in AS. The effect of nitrogen on quartz solubility has been demonstrated to be negligible.

Screening of conformational polymorphism of ibuprofen in supercritical CO2

The populations of conformers of ibuprofen in supercritical CO2 have been calculated for two isochors in the temperature range of 35–90°C, using the combination of data of IR spectroscopy, quantum chemical calculations and molecular dynamics simulation (metadynamics approach). The results of 2D cross-correlation analysis of IR spectra confirm the presence of two spectral contributions associated with two conformers. The population of the first conformer (Conf. I) is found to be dominating within the investigated temperature range. Moreover, at the temperature of 60°C, for both studied isochors, the population of the first conformer reaches the maximum. The assumption about the correlation between the populations of conformers in supercritical media and population of polymorphs, which form during crystallization from certain initial state parameters, has been formulated and checked using analysis of micronized ibuprofen powder obtained by the method of rapid expansion of supercritical solution (RESS). The analysis of the microcrystalline ibuprofen, obtained by RESS, was performed by Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction (XRPD). Both methods lead to estimation of the polymorphs populations in accordance with the conformer populations at corresponding state parameters.

On the solvation properties of supercritical electrolyte solutions

A series of hydrothermal diamond anvil cell experiments was conducted to constrain the effect of anions (Cl−, F−) and cations (Mg+2, Na+) on the molecular structure of high temperature/-pressure fluids, and to express the extent of hydration as a function of solute's speciation and concentration at temperatures ranging from 400 to 800°C and pressures of 1.7 to 30.1kbar. Results reveal that hydrogen-bonding environments for H2O molecules in the first hydration shell of anions evolve from pure OH⋯O to dynamic mixtures with OH⋯X− (F−, Cl−). The distribution of the “OH⋯X−” structures (OH⋯O, OH⋯X−) is proportional to the concentration of dissolved anions; strongly dependent, however, on ionic speciation. To this end, the OH⋯O structures inside the hydration shell of F− are weaker than the OH⋯Cl− and OH⋯O in Cl−bearing solutions. On the contrary, cations (Na+, Mg2+) appear to impose a minimal effect on the Raman spectra of the OH⋯O structures. The thermodynamic stability of “OH⋯Cl−” environments shows a strong correlation with the activity of H2O, indicative of the localized effect of the Cl− electric field that decouples the hydration from the bulk water molecules. The enthalpy change required to rupture these H-bonding environments (ΔHOH⋯Cl−) provides a measure for the extent of ion hydration and constrains the solvation properties of supercritical electrolyte solutions. For example, the dominant presence of “OH⋯Cl− “ environments lowers the concentration of isolated water dipoles and contributes to the decrease in the dielectric constant of supercritical electrolyte solutions, which in turn, could suppress the solubility of hydrophobic non-polar aqueous species, such as SiO2(aq).

Spilling breakers in shallow water: applications to Favre waves and to the shoaling and breaking of solitary waves

A two-layer long-wave approximation of the homogeneous Euler equations for a free-surface flow evolving over mild slopes is derived. The upper layer is turbulent and is described by depth-averaged equations for the layer thickness, average fluid velocity and fluid turbulent energy. The lower layer is almost potential and can be described by Serre–Su–Gardner–Green–Naghdi equations (a second-order shallow water approximation with respect to the parameter $H/L$, where $H$ is a characteristic water depth and $L$ is a characteristic wavelength). A simple model for vertical turbulent mixing is proposed governing the interaction between these layers. Stationary supercritical solutions to this model are first constructed, containing, in particular, a local turbulent subcritical zone at the forward slope of the wave. The non-stationary model was then numerically solved and compared with experimental data for the following two problems. The first one is the study of surface waves resulting from the interaction of a uniform free-surface flow with an immobile wall (the water hammer problem with a free surface). These waves are sometimes called ‘Favre waves’ in homage to Henry Favre and his contribution to the study of this phenomenon. When the Froude number is between 1 and approximately 1.3, an undular bore appears. The characteristics of the leading wave in an undular bore are in good agreement with experimental data by Favre (Ondes de Translation dans les Canaux Découverts, 1935, Dunod) and Treske (J. Hydraul Res., vol. 32 (3), 1994, pp. 355–370). When the Froude number is between 1.3 and 1.4, the transition from an undular bore to a breaking (monotone) bore occurs. The shoaling and breaking of a solitary wave propagating in a long channel (300 m) of mild slope (1/60) was then studied. Good agreement with experimental data by Hsiao et al. (Coast. Engng, vol. 55, 2008, pp. 975–988) for the wave profile evolution was found.

Dense underflow into a lake or reservoir – supercritical flow solutions

Steady two-dimensional flow from an angled structure into a lake or a reservoir where the interface between the intrusion and the ambient fluid separates from a solid wall is considered. The fluid is assumed to be of finite depth and the incoming channel makes a downward angle α with the horizontal axis. This simple configuration provides a model for the plunging inflow and subsequent underflow of dense water in a reservoir or lake. Exact solutions are presented at infinite Froude number and compared with the solutions to the full nonlinear problem for supercritical flow. Limiting flows are found to separate from the upper boundary at a stagnation point, and regions of non-uniqueness in the solution domain are found.

Rapid expansion of TiO2 layers processed by supercritical solutions for dye sensitized solar cell applications

Abstract In this work, anatase-type TiO2 layers were prepared by deposition of precursor solution including titanium isopropoxide, ethanol and acetic acetylacetone on a FTO substrate using rapid expansion of supercritical solutions (RESS). The spraying to obtain a particulate coating of TiO2 was carried out at 65 °C and 180 bar of supercritical carbon dioxide environment. Then, thermal annealing at 550 °C for 2 h was applied to coated substrates to obtain desired phase composition. The structural and optical properties of the film were evaluated by XRD, SEM and UV-Vis. SEM observation showed that the photoanode film has porous microstructure with interconnected spherical TiO2 grains. TiO2 film has a band gap of 2.6 eV.

Ionic Effects on Supercritical CO2-Brine Interfacial Tensions: Molecular Dynamics Simulations and a Universal Correlation with Ionic Strength, Temperature, and Pressure.

For geological CO2 storage in deep saline aquifers, the interfacial tension (IFT) between supercritical CO2 and brine is critical for the storage security and design of the storage capacitance. However, currently, no predictive model exists to determine the IFT of supercritical CO2 against complex electrolyte solutions involving various mixed salt species at different concentrations and compositions. In this paper, we use molecular dynamics (MD) simulations to investigate the effect of salt ions on the incremental IFT at the supercritical CO2-brine interface with respect to that at the reference supercritical CO2-water interface. Supercritical CO2-NaCl solution, CO2-CaCl2 solution and CO2-(NaCl+CaCl2) mixed solution systems are simulated at 343 K and 20 MPa under different salinities and salt compositions. We find that the valence of the cations is the primary contributor to the variation in IFT, while the Lennard-Jones potentials for the cations pose a smaller impact on the IFT. Interestingly, the incremental IFT exhibits a general linear correlation with the ionic strength in the above three electrolyte systems, and the slopes are almost identical and independent of the solution types. Based on this finding, a universal predictive formula for IFTs of CO2-complex electrolyte solution systems is established, as a function of ionic strength, temperature, and pressure. The predicted IFTs using the established formula agree perfectly (with a high statistical confidence level of ∼96%) with a wide range of experimental data for CO2 interfacing with different electrolyte solutions, such as those involving MgCl2 and Na2SO4. This work provides an efficient and accurate route to directly predict IFTs in supercritical CO2-complex electrolyte solution systems for practical engineering applications, such as geological CO2 sequestration in deep saline aquifers and other interfacial systems involving complex electrolyte solutions.

ChemInform Abstract: Preparation of Pharmaceutical Co‐Crystals Through Sustainable Processes Using Supercritical Carbon Dioxide: A Review

AbstractReview: [74 refs.

Impact of rapid expansion of supercritical solution process conditions on the crystallinity of poly(vinylidene fluoride) nanoparticles

The rapid expansion of supercritical solution (RESS) process was used to produce poly(vinylidene fluoride) (PVDF) nanoparticles. PVDF was chosen since five different crystal phases (α, β, γ, δ, ε) have been reported in literature. The experiments were performed with a low molar mass polymer (Mn=1500gmol−1) that consists exclusively of α phase. The main objectives of this study were to examine the influence of process parameters, i.e. inner nozzle diameter, pre-expansion temperature and pressure on polymer crystallinity and crystal phase properties. Before and after micronization, the polymer was characterized by scanning electron microscopy, size-exclusion chromatography, differential scanning calorimetry and X-ray diffraction.The findings of our investigations clearly show that RESS enables the formation of submicron particles. Furthermore, under certain process conditions, i.e. higher expansion and cooling rates and thus small nozzle diameters, RESS induces a crystal phase transformation from α to the desired β phase. In opposite thereto, simple static treatment with scCO2 does not induce crystal phase transformation. Furthermore, average molar mass, dispersity and crystallinity of the RESS product was reduced due to the preferred extraction of low molar mass fractions.

Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection

To alleviate the harmful effects of radiations during occupational radiology, radiotherapy and diagnosis, radioprotective system with lower toxicity and extended activity is imperative. Trans-resveratrol (RVL) acts through free radical scavenging/antioxidant mechanism to mitigate the radiation-induced damage. But, its poor solubility and fast metabolism impede its efficacy. Thus, encapsulation of RVL into long circulating solid lipid nanoparticle (SLN) is aimed. Supercritical CO2 solution of RVL, Gelucire®50/02 and Gelucire®50/13 SLN, was rapidly expanded into aqueous phase containing Tween 80, sonicated and lyophilized to get SLN. Particle size, polydispersity index (PDI), entrapment efficiency (%EE), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), drug release, in vivo pharmacokinetics, antioxidant assays, radiation-induced lipid peroxidation and plasmid DNA relaxation assays were studied. Stability studies were performed to analyze drug degradation and shelf life. Optimized formulation (F9) had %yield, particle size, PDI, %EE and %drug release (after 72 h) of 68.48 ± 5.73 %, 276.7 ± 5.33 nm, 0.18 ± 0.032, 62.66 ± 4.52 % and 70.05 ± 3.003 %, respectively. Electron microscopy revealed nearly spherical particles, while DSC and XRD showed reduced crystalline peaks. F9 showed higher AUC and sustained release of RVL in rats (i.v. bolus) and increased antioxidant activities and radioprotection as compared to RVL solution. Shelf life of >2 years was predicted for F9 (at 8 °C). Results are encouraging to use F9 for radiation exposure prophylaxis.

X-ray absorption spectroscopy studies in supercritical aqueous solutions

ABSTRACTThe past two decades have witnessed significant advances in the application of X-ray absorption spectroscopy (XAS) to the study of supercritical aqueous fluids. The data obtained using in situ XAS have provided insights into the stability and the structure of metal complexes that are fundamental to understanding natural and industrial hydrothermal processes. Important recent advances using XAS can be attributed to the use of new high temperature and pressure autoclaves designed specifically for the analysis of fluids at extreme temperatures and pressures, improved techniques for the acquisition of X-ray absorption spectra and molecular-level computational modelling used in association with XAS analysis. High-brilliance light sources have not only provided new opportunities for XAS investigations of supercritical fluids, but have also revealed the effects of beam-induced radiolysis of the same fluids. The advent of energy-dispersive and rapid-acquisition XAS holds promise for future studies of beam-induced radiolysis and of the kinetics associated with the formation of metal complexes in high-temperature fluids.