Supercritical Antisolvent Precipitation Research Articles

Supercritical Antisolvent Precipitation of Ampicillin in Complete Miscibility Conditions

Microparticles of ampicillin have been precipitated by a supercritical antisolvent process (SAS) using carbon dioxide and N-methylpyrrolidone as the antisolvent and solvent, respectively. The mean particle size (PS) and particle size distribution (PSD) of the processed antibiotic were chosen as responses to evaluate the process performance. The levels for a screening design of experiments were chosen to allow the process to take place in a single supercritical phase. Under these conditions, all of the experiments led to the successful precipitation of ampicillin. Concentration was a key factor as this had the most marked effect on both PS and PSD.

Synthesis of high surface area CuMn2O4 by supercritical anti-solvent precipitation for the oxidation of CO at ambient temperature

A series of high surface area nanocrystalline copper manganese oxide catalysts have been prepared by supercritical anti-solvent (SAS) precipitation using CO2 and tested for the ambient temperature oxidation of CO. The catalysts were prepared by precipitation from an ethanol/metal acetate solution and the addition of small quantities of water was found to result in a mixed acetate precursor with surface areas >200 m2 g−1, considerably higher than those prepared by conventional precipitation methods. The surface area of the final calcined mixed oxide was found to be dependent upon the initial water concentration. XRD and FT-IR analysis indicated that the addition of water promoted the formation of carbonate species in the amorphous acetate precursor, with high resolution TEM and STEM showing the material to consist of spherical agglomerations of fibrous strings of ca. 30 nm length. This is in contrast to the material prepared in the absence of water, using the same SAS methodology, which typically yields quasi-spherical particles of 100 nm size.

Purification of algal anti-tyrosinase zeaxanthin from Nannochloropsis oculata using supercritical anti-solvent precipitation

This work investigated the changes in content of algal zeaxanthin in submicronized precipitates generated from the supercritical anti-solvent (SAS) process of extracting microalgae Nannochloropsis oculata. Following a reverse phase elution chromatography, the particulates were successfully generated from feed solutions containing zeaxanthin that ranged from 0.4 to 0.8mg/mL by a SAS process. The precipitation condition was set at 323K and pressures ranged from 10 to 20MPa. Experimental results of a three-factor center composite response surface method for the SAS process indicated that the size of the precipitates was significantly affected by the flow rate of carbon dioxide. The purity of zeaxanthin increased with increasing solvent flow rate and with reducing solution concentration. The recovery of zeaxanthin and the morphology of the precipitates was also examined. The content of zeaxanthin in submicronsized precipitates increased from 485.9 (48.6%) to 673.7mg/g (67.4%). This work demonstrates that elution chromatography coupled with a SAS process is an environmentally benign method to recover anti-tyrosinase zeaxanthin from Nannochloropsis oculata as well as to generate submicrosized precipitates of the purest zeaxanthin from algal solutions.

Nanostructured cellulose acetate filaments produced by supercritical antisolvent precipitation

The supercritical antisolvent precipitation technique was used to precipitate cellulose acetate in form of nanostructured filaments. Two different solvents were used: acetone, chosen because it is a typical laboratory solvent, and a mixture acetic acid+water, that is industrially used in the cellulose acetylation process. The influence of the operating parameters, such as concentration of the liquid solution, pressure and temperature, on the structure of cellulose acetate filaments was studied. Several centimeter long structures, formed by nanoelements ranging from about 50 to 250nm, were obtained. Some experiments were replicated on a pilot plant to demonstrate the scalability of the process.

Coprecipitation of Cefuroxime Axetil–PVP composite microparticles by batch supercritical antisolvent process

Batch supercritical antisolvent precipitation (SAS) process was used to coprecipitate Cefuroxime Axetil amorphous (CFA, antibiotic) and Polyvinylpyrrolidone (PVP-K30) for preparing drug–polymer composite particles. Solutions of CFA and PVP-K30 in methanol with overall concentrations of 50–150mg/ml and polymer/drug ratios of 1/1–4/1 were sprayed into the CO2 at 70–200bar and 35–50°C with drug+polymer solution injection rates of 0.85 and 2.5ml/min. Spherical particles having mean diameters of 1.88–3.97μm, distribution ranges of 0.82–9.7μm (the narrowest distribution) and 0.91–46.64μm (the broadest distribution) were obtained. Mean particle size was not affected significantly with the change of process parameters. It was only affected by pressure change. On the other hand particle size distribution was affected by pressure, temperature, drug+polymer solution injection rate and concentration. It was observed that temperature and polymer/drug ratio affected the particle morphology most. The drug release rate of SAS-coprecipitated CFA–PVP (1/1) particles was almost 10 times slower than the drug alone. As the ratio of the polymer increased drug release rate also increased due to the wetting effect of PVP.

Loading of Bacterial Cellulose Aerogels with Bioactive Compounds by Antisolvent Precipitation with Supercritical Carbon Dioxide

AbstractBacterial cellulose aerogels overcome the drawback of shrinking during preparation by drying with supercritical CO2. Thus, the pore network of these gels is fully accessible. These materials can be fully rewetted to 100% of its initial water content, without collapsing of the structure due to surface tension of the rewetting solvent. This rehydration property and the high pore volume of these material rendered bacterial cellulose aerogels very interesting as controlled release matrices. Supercritical CO2 drying, the method of choice for aerogel preparation, can simultaneously be used to precipitate solutes within the cellulose matrix and thus to load bacterial cellulose aerogels with active substances. This process, frequently termed supercritical antisolvent precipitation, is able to perform production of the actual aerogel and its loading in one single preparation step. In this work, the loading of a bacterial cellulose aerogel matrix with two model substances, namely dexpanthenol and L‐ascorbic acid, and the release behavior from the matrix were studied. A mathematical release model was applied to model the interactions between the solutes and the cellulose matrix. The bacterial cellulose aerogels were easily equipped with the reagents by supercritical antisolvent precipitation. Loading isotherms as well as release kinetics indicated no specific interaction between matrix and loaded substances. Hence, loading and release can be controlled and predicted just by varying the thickness of the gel and the solute concentration in the loading bath.

Organic nanoparticles recovery in supercritical antisolvent precipitation

One of the major problems in dry nanoparticles production and handling is their recovery. Indeed, they tend to disperse in all the precipitation chamber and, due to their dimensions, are very difficult to collect. Supercritical antisolvent precipitation (SAS) was frequently used to produce nanoparticles at very mild conditions of pressure and temperature, but the issues of sedimentation mechanisms and nanoparticles recovery as single units, have not been evaluated yet. In this work, SAS nanoparticles were produced for samarium acetate, rifampicin, astemizole, amoxicillin trihydrate, tetracycline hydrochloride, clemastine, cellulose acetate and disperse red 60; the powders were collected as aggregates, due to the specific sedimentation mechanism that characterizes the process. SAS produced nanoparticles of the previously listed materials were precipitated from different organic solvents. Then, they were post-processed by ultrafiltration, ultracentrifugation and ultrasound based techniques, demonstrating that they can be easily separated in single nano-units. Nanoparticles showed mean diameters in the range 50–150 nm.

Supercritical antisolvent precipitation of andrographolide from Andrographis paniculata extracts: Effect of pressure, temperature and CO 2 flow rate

Andrographis paniculata extracts were precipitated using the so-called supercritical antisolvent (SAS) technique. Ethanol was used as the solvent and compressed CO 2 as the antisolvent. The effects of process operating conditions (pressure: 5–24 MPa, temperature: 308–328 K and CO 2 flow rate: 0.5–1.5 g/min) on particle size and morphology of precipitated andrographolide were evaluated. X-ray diffraction (XRD) patterns showed significant changes in andrographolide morphology depending on process operating conditions; both column-like and slice-like crystals were observed depending on operating conditions. Crystals with mean diameters of 3.30–228.35 μm were produced, smaller crystals were obtained at high pressure, low temperature and high CO 2 flow rate and vice versa for large crystals. In addition, SAS process also produced high precipitation yields, since solubility of andrographolide is small in the supercritical CO 2 plus ethanol. When operating under subcritical conditions, amorphous particles were produced.

Controlled precipitation and purification of hemicellulose from DMSO and DMSO/water mixtures by carbon dioxide as anti-solvent

Anti-solvent precipitation of xylans and mannans from dimethylsulfoxide (DMSO) or DMSO/water mixtures, and subsequent drying with supercritical carbon dioxide (scCO 2) were developed into a useful technique for preparing spherical hemicellulose micro-particles. Depending on the type of hemicellulose, water content of DMSO, precipitation pressure and temperature, the particle size can be adjusted within a wide range from less than 0.1 to more than 5 μm. For example, fast super-saturation which can be achieved by applying supercritical conditions results in the formation of very small particles as mass transfer between the solvent DMSO and anti-solvent scCO 2 is reduced to a minimum. Anti-solvent precipitation from aqueous DMSO (e.g., 10% water) allows for processing distinctly larger amounts of hemicelluloses compared to pure DMSO without the necessity of increasing the precipitation pressure. The formation of an additional inert aqueous phase increases the mass transfer resistance, which results in the formation of larger, stable agglomerates. Curiepoint pyrolysis GC/MS, gel permeation chromatography (GPC) and analysis of the monosaccharide composition of both the parent hemicellulosic material and the corresponding precipitates demonstrated that hemicelluloses can be purified from residual lignin by supercritical anti-solvent precipitation with carbon dioxide without altering the structure of the biopolymers.

Preparation of poly-lactic acid nano/microparticles using supercritical anti-solvent with enhanced mass transfer

Supercritical anti-solvent precipitation with enhanced mass transfer (SAS-EM) was applied for the production of micro and sub-microparticles of poly-lactic acid (PLA). SAS-EM technique uses an ultrasonic vibrating surface to enhance mass transfer rate between supercritical CO 2 and solvent. Without applying ultrasonic power, which is same as SAS process, PLA particles with average diameters ranging between 1 μm and 3 μm were obtained. Using SAS-EM with the power supply of 200 W, spherical PLA particles smaller than 1 μm were obtained. The particle size was able to be controlled in the range of 0.4 μm–1.0 μm, by adjusting the power supply of ultrasonic field, the system pressure and temperature.

A combinational supercritical CO 2 system for nanoparticle preparation of indomethacin

An improved system using both supercritical antisolvent precipitation and rapid expansion from supercritical to aqueous solution (RESAS) was proposed to overcome the problem of low solubility of medicinal substances in scCO 2. When the ethanol solution with IMC was sprayed into the vessel purged with scCO 2, no precipitation of IMC was observed if the CO 2 pressure was more than 15 MPa at 40 °C. This indicates that very small droplets of the ethanol solution with IMC could disperse in the high pressure CO 2. After expansion into distilled water using an RESAS device, this same solution, in CO 2 at high pressure, produced submicron particles of IMC. For the pharmaceutical application, the IMC suspension was freeze-dried and re-dispersed to the aqueous media. SEM images of freeze-dried sample showed that the suspension was composed of submicron particles with 300–500 nm. Although the average particle size of re-dispersed IMC related significantly to the pressure and temperature in the vessel on scCO 2 processing, the freeze-dried sample of the IMC suspension after the treatment shows good redispersibility as a nanosuspension. This apparatus is found to be a promising way to produce fine crystals of IMC with a high yield.

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, CO 2 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.

New Nanocrystalline Cu/MnOx Catalysts Prepared from Supercritical Antisolvent Precipitation

AbstractSupercritical CO2 is used as an antisolvent to precipitate out nanostructured homogeneous mixtures of Cu2+ and Mn3+ with crystallites of 10–20 nm in diameter. Following calcination, this material forms a crystalline tetragonal spinel, CuMn2O4, with a branched chainlike structure with a length of 160–200 nm and diameters of approximately 40 nm. This new material is more than twice as active per unit surface area as the conventionally prepared hopcalite catalysts for the oxidation of carbon monoxide. This is the first time that homogeneous mixed oxides have been formed using this method.

Polymeric microparticles prepared by supercritical antisolvent precipitation

This work has as main objective the development of a model process to obtain microparticles of an acrylate–methacrylate copolymer (Eudragit L100 ® and Eudragit EPO ®) using supercritical carbon dioxide (SC-CO 2) as antisolvent (GAS). After studying the behaviour of the copolymers in SC-CO 2 at different operation conditions (pressure, temperature and presence of ethanol (EtOH)), efforts were invested in the optimization of Eudragit EPO ® precipitation from an organic solution using carbon dioxide as antisolvent in batch mode. After loading the precipitation vessel with a fixed quantity of the copolymer dissolution, the SC-CO 2 has been added until the pressure of operation has been reached. Three process parameters, namely, solution nature, presence of surfactants and organic solvent removal step, have been evaluated. Microparticles with mean diameter from about 2 to 12 μm are obtained.

Supercritical antisolvent precipitation from an emulsion: β-Carotene nanoparticle formation

Supercritical antisolvent precipitation of β-carotene from an oil-in-water emulsion in which the solute is dissolved in the droplets that confirm the dispersed phase has been studied, with the objective of producing particles with a mean particle size in the nanometer scale. The aim of the current research work was to confirm the possibility to control the particle size of the carotene + surfactant suspensions obtained with this process, with the initial drop size present in the emulsions. The final products were formed by particles with a mean size below 400 nm in suspension in an aqueous media, which was also the mean droplet size of the emulsion. This result suggests that produced particles are encapsulated in surfactant micelles. The final suspension was then lyophilized and observed by means of a scanning electron microscopy. In order to obtain a better comprehension of the process, a mass transfer model was developed. This model is based on previous observations of the evolution of the organic phase drop and the solute, obtained with a view cell.

Characterization of azacytidine/poly( l-lactic) acid particles prepared by supercritical antisolvent precipitation

A controlled azacytidine release system based on drug encapsulation with a polymer material has been prepared and characterized. The drug systems were prepared by precipitation from solutions, using supercritical CO 2 antisolvent technique operating in a semi-continuous mode. Azacytidine was dissolved in dimethylsulfoxide and poly-lactic acid in methylene chloride. The two solutions were mixed before being sprayed into the supercritical reactor. Experimental conditions were 40 °C for temperature, 11 MPa for pressure, and a CO 2 flow rate of 30 ml min −1. The precipitated drug–polymer particles were further characterized to determine the percentage of encapsulated drug and establish the delivery kinetics under various release conditions. A sustained delivery of the drug over a period of various hours was obtained. Besides, an improved stability of the coated drug with respect to the pure azacytidine was found, thus proving the suitability of this approach for dealing with unstable compounds.

Particle Size and Bulk Powder Flow Control by Supercritical Antisolvent Precipitation

The purpose of this study was to use silicas for controlling the particle size of a poorly soluble drug in the micrometer to submicrometer range and enhancing the flowability of those particles in a supercritical fluid process. The concept used consists in entrapping a fast precipitated drug into the silica pores and drying the resulting particles fast enough to avoid particle growth and ensure proper size control. Because silica will also enhance the bulk density, it will help in inducing higher flowability to the final product. To prove this concept, a suspension containing a poorly soluble drug and silica was processed using the batch gas antisolvent (GAS) method. Griseofulvin (GF) was used as a model of a poorly water-soluble drug substance, and two types of silica with different pore size and particle size, respectively, were tested. Each experiment was performed at various drug/silica ratios to determine the optimal ratio for particle size control. The products of each experiment were then analyzed using optical microscopy, X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In addition, differential scanning calorimetric tests and dissolution rate studies were performed. Increasing the drug/silica ratio results in more pronounced particle size reduction and is accompanied by a change in drug particle morphology. The produced powders with silica showed enhanced flowability by visual inspection with the naked eye when compared to the neat drug. However, the available data shows that the silica has strong affinity with GF particles and affects the dissolution profile even though GF particle size is reduced. Kinetics instead of thermodynamics seems to be the controlling parameter for GF particles. All the experiments in this work were conducted in batch process mode, and further exploration is planned using the continuous supercritical antisolvent (SAS) process. Quantitative analysis of flowability is also part of the future work.

Production of Polymorphs of Ibuprofen Sodium by Supercritical Antisolvent (SAS) Precipitation

Ibuprofen sodium has been successfully micronized using the supercritical antisolvent (SAS) process. The influence of different process and operating parameters such as pressure, temperature, concentration, flow ratios, mixer design, and precipitator size on product characteristics (purity, particle size and morphology, and polymorphism) has been analyzed. It has been shown that with an adequate selection of process conditions it is possible to selectively produce either crystalline rodlike particles with particle sizes of 1−5 μm, or amorphous spherical particles with particle sizes of about 500 nm.

Nanoencapsulation of Lutein with Hydroxypropylmethyl Cellulose Phthalate by Supercritical Antisolvent

Lutein was nano-encapsuled with hydroxypropylmethyl cellulose phthalate (HPMCP) to maintain its bioactivity and to avoid thermal/light degradation. Supercritical antisolvent precipitation was applied to prepare lutein/HPMCP nano-capsule. The effects of several operating parameters on the yield, lutein loading, encapsulation efficiency, particle size and particle size distribution of the nanocapsule were investigated. The mean diameter of nanocapsules ranged from 163 nm to 219 nm under appropriate experimental conditions. The result of scanning electron microscope showed that the nanocapsules were nearly spherical. The highest yield reached 95.35% when the initial concentration of lutein was saturated. The highest lutein loading of 15.80% and encapsulation efficiency of 88.41% were obtained under the conditions of 11 MPa, 40°C and C HPMCP: C lutein = 5:l. The results may promote the application of lutein in food industry.

Ceria prepared using supercritical antisolvent precipitation: a green support for gold–palladium nanoparticles for the selective catalytic oxidation of alcohols

CeO2 has been prepared from an acetate precursor by an antisolvent precipitation technique using supercritical CO2. The supercritically synthesized ceria support was used to prepare Au–Pd based catalysts for the selective oxidation of alcohols in solvent-free conditions using molecular oxygen as oxidant. The supercritically precipitated catalyst demonstrated high activity for alcohol oxidation, and it was much more active than catalysts prepared using a CeO2 support derived from the acetate through a non-supercritical synthesis route. The bimetallic Au–Pd supported catalyst was considerably more active than monometallic catalysts containing Au and Pd only. HAADF imaging and STEM–XEDS mapping showed that both Au and Pd metallic components were intimately mixed and uniformly highly dispersed over the supercritical nanocrystalline CeO2 support spheres. In contrast, the Au–Pd catalyst on the non-supercritical CeO2 support showed discrete uniform Au–Pd alloy particles with a size range of 50 to 150 nm. The homogeneous alloy particles were Au-rich and Pd-deficient as compared with the preparation ratio and a low number of highly dispersed Pd was also associated with the support. XPS data for the ceria supported catalysts confirmed the differences of metal dispersion and identified that in both cases the surface species present were Au0 and Pd2+. On extended re-use the non-supercritical Au–Pd/CeO2 catalyst showed sequential deactivation. On the contrary, the supercritical Au–Pd/CeO2 catalyst showed a significant increase of activity, and it was only during the third re-use that the activity was marginally lower than the fresh catalyst. After use the spherical morphology of nanocrystalline supercritical CeO2 started to increasingly break down, until the morphology started to resemble the CeO2 prepared by the non-supercritical route. Simultaneously there was an increase of the metal particle size on the supercritically prepared CeO2 support, as discrete Au-rich and Pd-rich bimetallic particles were formed, and there was a decrease of the metal content. XPS confirmed the loss of metal on use and showed that there was reduction of the ceria surface during use. The increase of activity with a corresponding loss of metal components indicates that the fresh catalyst contains Au and Pd in inactive forms, whilst the active sites have extremely high turnover frequencies.