A new approach to select solvents and operating conditions for supercritical antisolvent precipitation processes by using solubility parameter and group contribution methods

A new approach is proposed to select operating temperature and pressure for supercritical antisolvent particle precipitation based on solubility parameter calculated by group contribution methods and using only the critical properties of the solvent. Solubility parameters are also used to choose the most suitable organic solvent for a given application. Supercritical antisolvent precipitation operating conditions of 36 systems are investigated including 8 organic solvents (methanol, ethanol, acetone, DMSO, DCM, chloroform, NMP and acetic acid) and 6 solid solutes (atenolol, tartaric acid, flunisolide, paracetamol, amoxicillin and cholesterol) in the temperature and pressure ranges of 25⿿85 °C and 50⿿250 bar. The results show a good agreement between the experimental and calculated data for these systems. Although particle precipitation depends on several parameters such as mass-transfer rates and hydrodynamics, the focus of this work is on the role of thermodynamics to indicate the preliminary conditions for a successful antisolvent precipitation process. Validation and results of this new approach suggest that it can be a useful tool for a qualitative and completely predictive evaluation of supercritical antisolvent particle precipitation in a cheaper way than carrying out experimental runs.     

Manipulating the size,the morphology and the polymorphism of acetaminophen using supercritical antisolvent (SAS) precipitation

The supercritical antisolvent technology is used to crystallize paracetamol particles. Supercritical carbon dioxide (scCO₂) is used as antisolvent. Ethanol, acetone and mixtures of ethanol and acetone are used as solvents. The initial concentration of paracetamol in the solution was varied between 1 and 5 wt%, the composition of the ethanol/acetone solvent mixture between 50 and 90 wt% of ethanol and the operation pressure between 10 and 16 MPa at a temperature of 313 K. The most important finding is that the polymorph of paracetamol crystals can be adjusted between monoclinic and orthorhombic by varying the content of ethanol in the solution. The second important finding is that the occurrence of primary and secondary crystal structures can be explained solely by the overall supersaturation during the crystallization process. While X-ray diffraction was used to analyze the polymorph of the particles, their morphology was analyzed using scanning electron microscopy.     

Crystallization of silibinin from organic solutions using supercritical and aqueous antisolvents

Silibinin, an anticancer drug, was crystallized from organic solutions using supercritical and aqueous antisolvents. Silibinin was dissolved in acetone and ethanol at concentration range of 0.01–0.04 g/mL, and the drug solutions were placed in contact with two different antisolvents, carbon dioxide and water. The mixing of the drug solutions and antisolvents led to the prompt precipitation of silibinin in a solid crystal form. The experimental variables, such as temperature, solution concentration, mixing rate and solution/antisolvent volume ratio were manipulated. When the experiments were conducted with a supercritical antisolvent, the effects of external additives on the crystal habit were examined. α-d-Glucose penta acetate, triton X-100 and urea were added to the solution at concentration range of 0.001–0.003 g/mL as external additives. The temperature increase of 20 °C induced 25% increase in particle size. As the solution concentration was increased from 0.01 to 0.04 g/mL, the average particle size decreased from 35.5 to 22.0 μm in supercritical antisolvent experiments, while the particle size increased from 8.9 to 30.4 μm in aqueous antisolvent experiments. The use of different kinds of external additives resulted in different modifications of the particle shape and structures.     

Preparation and properties of AlN ceramic suspension for non-aqueous gel casting

A non-aqueous gel casting process based on the mixed solvent (ethanol and polyethylene glycol) and low-toxicity N,N-dimethylacrylamide (DMAA) was developed for an aluminum nitride (AlN) ceramic. In the present work, rheological properties of non-aqueous concentrated AlN suspensions were investigated in the presence of mixed solvent, dispersant, milling time, monomer and solid loading, in order to screen for the most suitable experimental conditions to obtain a good rheological behavior for gel casting. The results showed that the 50 vol% slurry with 0.2 wt% dispersant concentration, 2 h milling time, 6 wt% -monomer content, and a solvent ratio of 3:1, can meet the requirements for the casting process of AlN ceramic slurries. After being dried at 100 °C for 1 h, the optimum bulk density and maximum flexural strength of the AlN green bodies were as high as 1.97 g/cm³ and 18.68 MPa, respectively. SEM photographs revealed that the green body had a relative uniform microstructure when the solid loading was 50 vol%. The shrinkage and deformation of shaped sintered bodies prepared through gel casting were small after sintering. The sintering shrinkage, apparent porosity, bulk density and flexural strength were 14.8%, 0.22%, 3.21 g/cm³ and 310 MPa, respectively.     

Supercritical fluid extracts with antioxidant and antimicrobial activities from myrtle (Myrtus communis L.) leaves. Response surface optimization

Supercritical Fluid Extraction (SFE) was used to obtain myrtle leaf extracts, and to study the antioxidant capacity (AOC) and in vitro antimicrobial activity of those extracts. To optimize the SFE operational conditions, the response surface methodology (RSM) was adopted. The parameters studied were: pressure (P), within the range 10 to 30 MPa; temperature (T), between 35 °C and 60 °C and supercritical carbon dioxide (SCCO₂) flow rate (Q) within the range 0.15 to 0.45 kg h⁻¹. The results show a good fit to the proposed model and the optimal conditions obtained (23 MPa, 45 °C, and SCCO₂ flow rate of 0.3 kg h⁻¹) were within the experimental range. The predicted values agreed with experimental ones, thus indicating the suitability of the RSM model for the optimization of the extraction conditions being investigated. With those values remaining constant, ethanol as a co-solvent was then studied. There was an observed rise in AOC as the amount of ethanol increased, within the range studied (0–30 wt% ethanol). The extract with the highest AOC was tested for its antimicrobial activity against gram-positive and gram-negative bacteria. The minimum inhibitory concentration (MIC) values obtained showed significant inhibitory effect against gram-positive bacteria.     

Formation of PVP hollow fibers by electrospinning in one-step process at sub and supercritical CO2

It was well known that electrospinning is one of the simple technical methods for the production of polymer nanoparticles and nanofibers. Various polymers have been successfully electrospun into ultrafine particles and fibers in recent years mostly in solvent solution and some in melt form. In this work, hollow fibers with walls made of organic polymer composites have been formed by electrospinning in a single processing step under pressurized carbon dioxide (CO₂). The experiments were conducted at 313 K and ∼8 MPa. The capability and feasibility of this technique was demonstrated by the production of polyvinylpyrrolidone (PVP) fibers whose size and wall thickness could be independently varied by controlling a set of experimental parameters. The PVP fibers had an average pore diameter 2–4 μm. At low pressures (<5 MPa; subcritical conditions), the solid fibers were formed, the baloon-like structures of PVP was formed with increasing pressure of CO₂ at 8 MPa (supercritical condition)     

Optimization of essential oil supercritical extraction from Algerian Myrtus communis L. leaves using response surface methodology

The present work deals with the application of the supercritical fluid extraction process to extract essential oils from the leaves of an Algerian myrtle plant (Myrtus communis L.). Using the surface response methodology, an optimization of the extraction recovery was carried out, varying the pressure in the range of [10–30 MPa], the temperature within [308–323 K], a solvent flow rate fixed at 0.42 kg h⁻¹ and a mean particle diameter equal to 0.5 mm or less than 0.315 mm. The maximum value of essential oil recovery relative to the initial mass of leaf powder was 4.89 wt%, and was obtained when the SC–CO₂ extraction was carried out under 313 K, 30 MPa and with a particle diameter less than 0.315 mm. A second-order polynomial expression was used to express the oil recovery. The calculated mass of recovered oil using the response surface methodology was very close to the experimental value, confirming the reliability of this technique.     

Interactions of phase equilibria,jet fluid dynamics and mass transfer during supercritical antisolvent micronization

Supercritical antisolvent (SAS) precipitation has been successfully used in the micronization of several compounds. Nevertheless, the role of high-pressure vapor–liquid equilibria, jet fluid dynamics and mass transfer in determining particle size and morphology is still debated. In this work, CO₂ has been adopted as supercritical antisolvent and elastic light has been used to acquire information on jet fluid dynamics using thin wall injectors for the investigation of the liquid solvents acetone and DMSO at operating conditions of 40 °C in the pressure range between 6 and 16 MPa. The results show that two-phase mixing after jet break-up is the phenomenon that characterizes the jet fluid dynamics at subcritical conditions. When SAS is performed at supercritical conditions a transition between multi-phase and single-phase mixing is observed by increasing the operating pressure. Single-phase mixing is due to the very fast disappearance of the interfacial tension between the liquid solvent and the fluid phase in the precipitator. The transition between these two phenomena depends on the operating pressure, but also on the viscosity and the surface tension of the solvent. Indeed, single-phase mixing has been observed for acetone very near the mixture critical point, whereas DMSO showed a progressive transition for pressures of about 12 MPa.In the second part of the work, a solute was added to DMSO to study the morphology of the microparticles formed during SAS precipitation at the different process conditions, to find a correlation between particle morphology and the observed jet. Expanded microparticles were obtained working at subcritical conditions; whereas spherical microparticles were obtained operating at supercritical conditions up to the pressure where the transition between multi- and single-phase mixing was observed. Nanoparticles were obtained operating far above the mixture critical pressure. The observed particle morphologies have been explained considering the interplay among high-pressure phase equilibria, fluid dynamics and mass transfer during the precipitation process.     

Foaming strategies for bioabsorbable polymers in supercritical fluid mixtures. Part II. Foaming of poly(ɛ-caprolactone-co-lactide) in carbon dioxide and carbon dioxide + acetone fluid mixtures and formation of tubular foams via solution extrusion

This paper reports on the foaming of poly(ɛ-caprolactone-co-lactide) in carbon dioxide and carbon dioxide + acetone mixtures. Experiments were carried out in specially designed molds with porous metal surfaces and fluid circulation features to generate foams with uniform dimensions at 60, 70 and 80 °C at pressures in the range 7–28 MPa. Depending upon the conditions, foams with pores in the range from 5 to 200 μm were generated. Adding acetone to carbon dioxide improved the uniformity of the pores compared to foams formed by carbon dioxide alone. In addition, a unique high-pressure solution extrusion system was designed and used to form porous tubular constructs by piston-extrusion of a solution from a high-pressure dissolution chamber through an annular die into a second chamber maintained at controlled pressure/temperature and fluid conditions. Long uniform porous tubular constructs with 6 mm ID and 1 mm wall thickness were generated with glassy polymers like poly(methyl methacrylate) by extruding solutions composed of 50 wt% polymer + 50 wt% acetone, or 25 wt% polymer + 10% acetone + 65% carbon dioxide at 70 °C and 28 MPa. Pores were in the 50 μm range. The feasibility of forming similar tubular constructs were demonstrated with poly(ɛ-caprolactone-co-lactide) as well. Tubular foams of the copolymer with interconnected pores with pore sizes in the 50 μm range were generated by extrusion of the copolymer solution composed of 25 wt% polymer + 10 wt% acetone + 65 wt% carbon dioxide at 70 °C and 28 MPa. Reducing the acetone content in the solution led to a reduction of pore sizes. Comparisons with the foaming behavior of the homopolymer poly(ɛ-caprolactone) that were carried out in the molds with porous metal plates show that the foaming behavior of the copolymer is more akin to the foaming behavior of the caprolactone homopolymer component.     

Enzyme and high pressure assisted extraction of carotenoids from tomato waste

Enzyme (EA) and high pressure (HP) assisted extraction of carotenoids, especially lycopene, from tomato waste using various organic solvents was examined. Total carotenoid and lycopene extraction yields were increased by the use of pectinase and cellulase enzymes, when compared to the non enzyme treated solvent extraction process. The increase of extraction yield depended on the solvent. Maximum total carotenoid (127 mg/kg d.w.) and lycopene (89.4 mg/kg d.w.) extraction yields were obtained in enzyme treated samples extracted with ethyl lactate (solvent:solid = 10:1 mL:g), corresponding to almost 6-fold and 10-fold increase, respectively, with respect to non enzyme treated samples. HP assisted extraction led to higher extraction yields (from 2 to 64% increase depending on the solvent used) compared to conventional solvent extraction process performed at ambient pressure for 30 min. HP assisted solvent extraction was successfully performed at 700 MPa by using significantly (P < 0.05) lower ratios of solvent:solid (6:1 and 4:1 mL:g) and reduced processing time (10 min), compared to solvent extraction performed at ambient pressure, solvent:solid ratio 10:1 mL:g and 30 min extraction time.     

Extraction of jojoba seed oil using supercritical CO2+ethanol mixture in green and high-tech separation process

In this study, the extraction of jojoba seed oil obtained from jojoba seed using both supercritical CO₂ and supercritical CO₂+ethanol mixtures was investigated. The recovery of jojoba seed oil was performed in a green and high-tech separation process. The extraction operating was carried out at operating pressures of 25, 35 and 45 MPa, operating temperatures of 343 and 363 K, supercritical fluid flow rates of 3.33 × 10⁻⁸, 6.67 × 10⁻⁸ and 13.33 × 10⁻⁸ m³ s⁻¹, entrainer concentrations of 2, 4 and 8 vol.%, and average particle diameters of 4.1 × 10⁻⁴, 6.1 × 10⁻⁴, 8.6 × 10⁻⁴ and 1.2 × 10⁻³ m. It was found that a green chemical modifier such as ethanol could enhance the solubilities, initial extraction rate and extraction yield of jojoba seed oil from the seed matrix as compared to supercritical CO₂. In addition, it was found that the solubility, the initial extraction rate and the extraction yield depended on operating pressure and operating temperature, entrainer concentration, average particle size and supercritical solvent flow rate. The solubility of jojoba seed oil and initial extraction rate increased with temperature at the operating pressures of 35 and 45 MPa and decreased with increasing temperature at the operating pressure of 25 MPa. Furthermore, supercritical fluid extraction involved short extraction time and minimal usage of small amounts entrainer to the CO₂. About 80% of the total jojoba seed oil was extracted during the constant rate period at the pressure of 35 and 45 MPa.     

Influence of pretreatment on supercritical CO2 extraction from Nannochloropsis oculata

This work demonstrates that supercritical carbon dioxide extraction is efficient for the complete recovery of neutral lipids from microalgae with a water content up to 20 wt%, allowing thus a further full characterization of this oil. This is a first useful step in the framework of lipid production from microalgae either for nutraceutical, food or for energy applications. This study is particularly focused on the influence of the pretreatments upon extraction kinetics and yields. This study proposes a complete study at laboratory scale (10 g per batch of dry biomass) of the influence of pretreatments (type of drying and grinding) and of water content on the extraction kinetics and yields as well as on the oil composition in terms of lipidic classes and profiles. Two drying pretreatments (drying under air flow and freeze-drying) applied on Nannochloropsis oculata were studied. Extraction experiments were carried out at 40 MPa, 333 K, with a carbon dioxide flow rate of 0.5 kg h⁻¹ and for different granulometries. Results showed that drying under air flow at 308 K is the most adequate pretreatment leading to the most rapid kinetics. Whatever the pretreatment used, the extracted oil contains more than 90 wt% of triglycerides and does not contain phospholipids. As expected, the smaller the particle size, the faster the extraction kinetics. Finally, an increase in the biomass water content up to 20 wt% increases the global extraction kinetics (extraction of both water and oil) but appears to have no influence on oil extraction yields. Moreover, the extraction of neutral lipids happens to be complete for a CO₂/charge mass ratio ranging from 30 to 130 depending on the operating conditions and on the characteristics of the treated biomass. Finally, pilot scale experiments were performed with batches up to 15 kg in order to evaluate the influence of pressure and particle size on the extraction kinetics and yields. Extracts obtained at 333 K with operating pressures of 50 MPa and 85 MPa have similar compositions and do not contain phospholipids.     

Extraction of palm oil using propane,ethanol and its mixtures as compressed solvent

This work is aimed to investigate the extraction of palm oil using pressurized ethanol and propane as solvents. The effects of temperature (293⿿333 K), pressure (from 10 to 20 MPa), solvent flow rate (from 1 to 5 mL/min), and composition of the solvent mixture were evaluated on the oil extraction yield, and chemical profile of the extracted oils. The experiments were conducted in a 100 mL extractor coupled to a HPLC pump for ethanol and a syringe pump for the propane displacement. Global yields up to 75 wt% were obtained in the experiments. The kinetic profiles of the extractions were described by the Sovová⿿s model, which presented good agreement with the experimental observations. The palm oils extracted with distinct solvents were characterized regarding its density and viscosity in a temperature range from 293 to 343 K, its chemical profile determined by GC/MS, and carotenoid content.     

Dense CO2 antisolvent precipitation of levothyroxine sodium: A comparative study of GAS and ARISE techniques based on morphology and particle size distributions

Morphology and particle size distribution of levothyroxine sodium are experimentally investigated by comparing gas antisolvent (GAS) and atomized rapid injection for solvent extraction (ARISE) techniques using dense CO₂. Precipitation of levothyroxine sodium from ethanol was carried out at 25, 40 and 50 °C, with pressure in the 90–120 bar range and different concentrations of the organic solution. Particles produced by the GAS process are nanospheres whereas ARISE processed particles are either spherical or rod-like micro and nanoparticles. Particle size and size distributions of GAS processed levothyroxine sodium are in the 370–500 nm range, while the ARISE process produced particles in the 360–1200 nm range. In most cases, both techniques produced bimodal size distributions, due to particle agglomeration. The different morphological characteristics and particle size distributions of levothyroxine sodium obtained using GAS and ARISE at different operating conditions can be useful depending on the type of drug formulation chosen, as well as the route of drug administration and delivery system.     

The use of polyacrylamide-aluminosilicate composites for thorium adsorption

The adsorption of Th⁴⁺ ions was studied on composites of polyacrylamide (PAAm) with montmorillonite (Mt), clinoptilolite (Z) and zeolite Y (ZY), and after phytic acid (Phy) modification.The monolayer adsorption capacity was 0.33 and 0.65 mol kg^? 1 for PAAm-Mt and PAAm-Mt-Phy, 0.07, 0.21 and 0.60 mol kg^? 1 for Z, PAAm-Z and PAAm-Z-Phy, and 0.74, 0.89 and 1.18 mol kg^? 1 for ZY, PAAm-ZY and PAAm-ZY-Phy. The enthalpy and entropy changes were positive for all adsorbents. The adsorption kinetics followed the pseudo-second order model indicating that the rate controlling step was chemical adsorption by ion exchange. The reusability tests for five uses proved that the PAAm-Mt and PAAm-Z were reusable and complete recovery of the adsorbed ions was possible. ZY and the composites modified with Phy were not reusable. The presence of foreign metal cations did not influence the Th⁴⁺ adsorption. The adsorbed Th⁴⁺ onto the columns was effectively recovered with diluted HNO₃.     

Temperature induced gelation of non–aqueous alumina suspension using oleic acid as dispersant

A novel temperature induced gelation method for alumina suspension using oleic acid as dispersant is reported. Non–aqueous suspension with high solid loading and low viscosity is prepared using normal octane as solvent. Influence of oleic acid on the dispersion of suspension was investigated. There was a well disperse alumina suspension with 1.3 wt% oleic acid. Influence of gelation temperature on the coagulation process and properties of green body was investigated. The sufficiently high viscosity to coagulate the suspension was achieved at −20 °C. The gelation temperature was controlled between the melting point of dispersant and solvent. The gelation mechanism is proposed that alumina suspension is destabilized by dispersant separating out from the solvent and removing from the alumina particles surface. The alumina green body with wet compressive strength of 1.07 MPa can be demolded without deformation by treating 53 vol% alumina suspension at −20 °C for 12 h. After being sintered at 1550 °C for 3 h, dense alumina ceramics with relative density of 98.62% and flexural strength of 371±25 MPa have been obtained by this method.     

Extraction of bioactive components from Centella asiatica using subcritical water

Bioactive components, asiatic acid and asiaticoside, were extracted from Centella asiatica using subcritical water as an extraction solvent. Extraction yields of asiatic acid and asiaticoside were measured using high-performance liquid chromatography (HPLC) at temperatures from 100 to 250 °C and pressures from 10 to 40 MPa. As temperature or pressure increased, the extraction yield of asiatic acid and asiaticoside increased. At the optimal extraction conditions of 40 MPa and 250 °C, the extraction yield of asiatic acid was 7.8 mg/g and the extraction yield of asiaticoside was 10.0 mg/g. Extracted asiatic acid and asiaticoside could be collected from water as particles with a simple filtering process. Dynamic light scattering (DLS) was used to characterize particle size. Particles containing asiatic acid were larger (1.21 μm) than particles containing asiaticoside (0.76 μm). The extraction yields of asiatic acid and asiaticoside using subcritical water at 40 MPa and 250 °C were higher than extraction yields using conventional liquid solvent extraction with methanol or ethanol at room temperature while the subcritical water extraction yields were lower than extraction yields with methanol or ethanol at its boiling point temperature.     

Supercritical extraction of carob kibbles (Ceratonia siliqua L.)

Carob pulp kibbles, a by-product of carob been gum production, was studied as a source of bioactive agents. Firstly, the carob kibbles were submitted to an aqueous extraction to extract sugars, and supercritical fluid extraction (SFE) was applied to the solid residue of that aqueous extraction, by using compressed carbon dioxide (SC-CO₂) as the solvent and a mixture of ethanol and water (80:20, v/v) as a co-solvent. Pressure and temperature were studied in the ranges 15–22 MPa, and 40–70 °C. Particle diameter, and co-solvent percentage in ranges of 0.27–1.07 mm, and 0–12.4%, respectively, were also studied, as well as the flow rate of SC-CO₂ between 0.28 and 0.85 kg h⁻¹, corresponding, respectively, to 0.0062 and 0.0210 cm s⁻¹ of superficial velocity. The extracts were characterised in terms of antioxidant capacity by DPPH method, and total phenolics content by the Folin–Ciocalteu method. The central composite non-factorial design was used to optimise the extraction conditions, using the Statistica, version 6 software (Statsoft). The best results, in terms of yield and antioxidant capacity, were found at 22 MPa, 40 °C, 0.27 mm particle size, about 12.4% of co-solvent and a flow rate of 0.29 kg h⁻¹ of SC-CO₂. The phenolics profile of the extracts obtained at these conditions was qualitatively evaluated by HPLC-DAD. The solid residue of the supercritical extraction was also studied showing to be a dietary fiber, which can be compared to Caromax™, a carob fiber commercialised by Nutrinova Inc.     

Fabrication of transparent yttria ceramics by alcoholic slip-casting

Y₂O₃ transparent ceramics were prepared from alcoholic slurries of Y₂O₃ nanopowders via a slip-casting method to avoid the hydrolysis issue. Polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG) and polyethylenimine (PEI) were used as dispersants to improve the rheological properties of the slurries. It was found that PEI is the most effective dispersant in ethanol. The adsorbed amount of PEI was evaluated by infrared absorption and rheology measurements. Y₂O₃ slurry with a solid loading of 20.8 vol% and a viscosity of <0.1 Pa s at the shear rate of 10 s⁻¹ was obtained using 1.5 wt% PEI. The slurry yielded a homogeneous green body, and finally resulted in a high-quality Y₂O₃ ceramic with the in-line transmittance of 80% at 800 nm.     

Microstructured ternary solid dispersions to improve carbamazepine solubility

The aim of this study was to investigate the improvement of the aqueous solubility of carbamazepine by preparing microstructured ternary solid dispersions using polyoxylglycerides and colloidal silicon dioxide. Microstructured solid dispersions were obtained in a spray dryer. The influence of the spray drying conditions on the properties of the microparticles was investigated using a full 3² factorial design in which the factors studied were the silicon dioxide content and the air outlet temperature. The microparticles were thoroughly characterized in terms of yield, solubility, angle of repose, particle size, drug content, moisture content, sorption isotherms, morphology, thermal behavior, infrared spectroscopy and crystallinity. The dissolution rates of carbamazepine and of the microparticles in water were also determined. In general, the microstructured solid dispersions demonstrated good yield, adequate flow and moisture content (< 3%), drug recovery (91.98 to 100.22%) and particle size (< 142.90 μm). Thermal and infrared analysis showed that there was no drug interaction during the process. On the other hand, the results of X-ray diffraction evidenced a partial polymorphic modification of carbamazepine. The solubility and dissolution rates of carbamazepine were remarkably improved. Therefore, the results confirm the high potential of the spray drying technique to obtain microstructured ternary solid dispersions.