Supercritical Antisolvent Technique Research Articles

CeO2-CuO composites prepared via supercritical antisolvent precipitation for photocatalytic hydrogen production from lactic acid aqueous solution

The global increase in energy demand requires a continuous search for renewable and clean alternative resources to fossil fuels. Hydrogen is emerging as a promising energy carrier for the future; its production via photocatalysis, driven by sunlight, can directly convert solar energy into a usable or storable energy resource. However, water splitting requires sacrificial agents or electron donors/hole scavengers, such as short-chain organic acids. This research explores the use of lactic acid as a source for photocatalytic hydrogen production, offering valuable alternatives for wastewater management and renewable energy production. This study employed the innovative supercritical antisolvent (SAS) technique to micronize the precursors of both the active phase (CeO2) and co-catalyst (CuO), ensuring rapid and complete solvent removal and size reduction of photocatalyst precursors. The prepared samples were characterized by field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) analysis, Brunauer-Emmett-Teller (BET) analysis and thermogravimetric analysis (TGA). This study has shown that the micronization process resulted in a notable improvement in CeO2 photocatalytic activity, attributed to the reduction of the dimensions of the powders. Hydrogen production was equal to 3989 μmol L−1 for the SAS-produced photocatalyst while using a commercial CeO2 sample resulted in H2 production of 2519 μmol L−1. The enhanced photoactivity of CeO2-CuO composites was found to be related to the presence of CuO. The optimal CuO amount was equal to 0.5 wt%, determining a hydrogen production of 9313 μmol L−1 after 4 h of UV irradiation time. A photocatalytic test carried out with deuterated water (D2O) instead of distilled H2O demonstrated that hydrogen was preferentially produced from water splitting reaction, whereas lactic acid acted as a sacrificial agent being oxidized from positive holes photogenerated in the valence band of CuO.

Biosensing of Cysteine through the Induction of Oxygen Vacancies in a Cu/Zr Heterostructure Prepared by Supercritical Antisolvent Technique.

There has been a growing emphasis on facile preparation of binary heterogeneous composite materials. Leveraging the eco-friendly efficiency of supercritical CO2 technology, we achieved precise control over the influencing factors of mass transfer, enabling the accurate modulation of the resulting product morphology and properties. In the current study, CuxO/ZrOy composite materials were prepared using this technology and calcined to obtain electrode materials for the detection of cysteine (Cys). Essential comprehensive characterization techniques were employed to elucidate the heterojunction. The resulting electrode demonstrated a linear response to Cys within a concentration range of 0.5 nM to 1 μM, featuring a high sensitivity of 1035 μA·cm-2·μM-1 and a low detection limit of 97.3 nM. Thus, establishing a novel avenue for nonenzyme-based electrochemical sensors tailored for biologically active Cys detection through the implementation of a heterogeneous structure.

Solubility of oxazepam in supercritical carbon dioxide: Experimental and modeling

This study thoroughly investigates the solubility of oxazepam in supercritical carbon dioxide (SC-CO2) at temperatures of 308, 318, 328, and 338 K and pressures ranging from 12 to 30 MPa. The solubility measurements revealed a mole fraction of oxazepam ranging from 2.50 × 10−6 to 7.13 × 10−5, with the highest solubility observed at 338 K and 30 MPa. The solubility data were effectively modeled using semi-empirical density-based models (Mendez-Santiago and Teja (MST), Chrastil, Bartle et al., Kumar and Johnston (K-J), and Alwi-Garlapati), two equations of state (Peng-Robinson and modified-Pazuki) and regular solution models. The K-J model emerged as the best fit for the experimental data, boasting the lowest Average Absolute Relative Deviation (AARD) value of 7.73 %. The Peng-Robinson equation of state outperformed the modified-Pazuki equation, with AARD values of 15.71 % and 18.15 %, respectively. The study's key finding is the low solubility of oxazepam in SC-CO2, which suggests that supercritical antisolvent techniques could be effectively employed for synthesizing nanoparticles of this pharmaceutical compound. These findings have practical implications as they provide valuable insights for optimizing drug formulation processes and demonstrate the potential of SC-CO2 in pharmaceutical applications.

Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of –33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.

Curcumin/Carrier Coprecipitation by Supercritical Antisolvent Route.

In this work, polyvinylpyrrolidone (PVP)- and β-cyclodextrin (β-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 μm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using β-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 μm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ β-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that β-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and β-CD have an improved release rate.

Design of esomeprazole solid dispersion for improved dissolution and bioavailability using the supercritical anti-solvent technique

Design of esomeprazole solid dispersion for improved dissolution and bioavailability using the supercritical anti-solvent technique

A Brief Review of the Supercritical Antisolvent (SAS) Technique for the Preparation of Nanocatalysts to Be Used in Biodiesel Production

In an era where sustainability is becoming the main driving force for research and development, supercritical fluids-based techniques are presented as a very efficient alternative technology to conventional extraction, purification, and recrystallization processes. Supercritical antisolvent (SAS) precipitation is a novel technique that can replace liquid antisolvent precipitation techniques. Additionally, through the optimization of precipitation operating conditions, morphology, particle size, and particle size distribution of nanoparticles can be controlled. As an antisolvent, supercritical carbon dioxide (scCO2) is far more sustainable than its conventional liquid counterparts; not only does it have a critical point (304 K and 73.8 bar) on its phase diagram that allows for the precipitation processes to be developed so close to room temperature, but also its recovery and, consequently, the precipitated solute purification stage is considerably simpler. This technique can be used efficiently for preparing nanocatalysts to be used in biodiesel production processes.

Production of hybrid TiO2/β-CD photocatalysts by supercritical antisolvent micronization for UV light-driven degradation of azo dyes

The aim of this work was to obtain hybrid photocatalysts by combining micronized β-cyclodextrin (β-CD) with TiO2 (PC500). β-CD was micronized using the supercritical antisolvent technique (SAS) to observe the influence of the solute concentration on the hybrid photocatalysts’ morphology. At all the β-CD concentrations, the photocatalyst was constituted of microparticles (mean diameter=1.6–2.1 µm). The photocatalysts were analyzed by various chemical-physical characterization techniques. In particular, wide angle X-ray diffraction and Raman analyses showed the presence of the anatase phase characteristic of commercial PC500. Moreover, FT-IR spectra highlighted the interaction between β-CD and PC500. Photocatalytic performances are evaluated in the UV-light degradation of Acid Orange 7 azo dye. The addition of micronized β-CD improves the photocatalytic activity of bare PC500. Indeed, the optimized hybrid photocatalyst exhibited the complete color removal and the highest mineralization efficiency (96%) under UV irradiation. In addition, the optimized PC500/CD SAS50 sample proved to be stable and reusable.

Dispersion of bioactive substances in oils by supercritical antisolvent technology (BIOSAS process)

This work presents the novel method named BIOSAS to formulate homogenous dispersions of bioactive substances in an oily matrix. The method is based on the carbon dioxide supercritical antisolvent (SAS) technique to produce small drops of a solution containing the bioactive substances, in the presence of a lipid substance. Ethanolic and aqueous solutions were used to solubilize complex mixtures of phytochemicals depending on the polarity of compounds. Ethanol was removed entirely from the droplets by SAS effect, and solid bioactive particles with mean diameters below 1 μm were uniformly dispersed in the lipid matrix; for aqueous solutions, the water droplets produced were high-pressure mixed with the lipid phase containing an emulsifier, and stable emulsions were obtained. BIOSAS permits particle size control and can be used to formulate lipid-based nutraceuticals or food supplements in an inert atmosphere and at low temperatures, contributing to reducing the oxidation and thermal degradation of bioactive substances and lipid matrix.

Control some foodborne pathogens, contaminated bacteria and fungi by fabrication calyx cape gooseberry (Physalis peruviana L.) nanoparticles

We studied the effect of the calyx of cape gooseberry nanoparticles manufactured by a novel technique. There are several methods, such as jet mill, spray freezing, supercritical anti-solvent technique (SAS), and high-pressure homogenization, available for the production of drug micro/nanoparticles to improve drug solubility. Anti-solvent precipitation is also used to prepare micro- and nanosized particles to explain their effects on different foodborne pathogens, contaminated bacteria, and some fungi. Results indicated that nanoparticles of the cape gooseberry calyx contained higher antioxidant activity than that found in the normal calyx, seed, and juice. While studying the effect of cape gooseberry calyx nanoparticles on microorganisms, it was found that the zone of inhibition was highly positive against Bacillus cereus, B. subtilis, Staphylococcus aureus, Clostridium perfringens, and Salmonella typhimurium compared to that of the normal cape gooseberry calyx. All species of molds, including Mucor sp., Aspergillus niger, Penicillium sp., and Alternaria sp., and yeasts like Saccharomyces cerevisiae and Rhodotorula glutinis were affected by nanoparticles of the cape gooseberry calyx compared to those of the normal calyx.

Applications of Supercritical Anti-Solvent Process in Preparation of Solid Multicomponent Systems.

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle solid-state properties, such as size, morphology, and crystal form is required to optimize the SMS formulation. By utilizing the unique and tunable properties of supercritical fluids, supercritical anti-solvent (SAS) process holds great promise for the manipulation of the solid-state properties of APIs. The SAS techniques have been developed from batch to continuous mode. Their applications in SMS preparation are summarized in this review. Many pharmaceutical co-crystals and solid dispersions have been successfully produced via the SAS process, where the solid-state properties of APIs can be well designed by controlling the operating parameters. The underlying mechanisms on the manipulation of solid-state properties are discussed, with the help of on-line monitoring and computational techniques. With continuous researching, SAS process will give a large contribution to the scalable and continuous manufacturing of desired SMS in the near future.

Simultaneous formation of inclusion complex and microparticles containing Albendazole and β-Cyclodextrin by supercritical antisolvent co-precipitation

Albendazole (ABZ) is an effective anthelmintic and an anticancer candidate. Due to the low oral bioavailability associated with its poor aqueous solubility, high doses are required, and dose-related side effects are reported. To enhance ABZ dissolution different formulation approaches were proposed, among others, its combination with cyclodextrins. In this work, co-precipitation of β-cyclodextrin and ABZ was performed by supercritical antisolvent technique as an alternative preparation method. The operating temperature and pressure of the experiments were selected by thermodynamic modeling with the purpose of obtaining a miscible solution between solvent mixture (DMSO + acetone) and CO2. Precipitated microparticles were characterized by spectroscopic, thermal, and crystallographic analysis in order to demonstrate the formation of a new solid form. The characterization evidenced that tautomer II of ABZ was obtained by precipitation in supercritical CO2 medium. The change of the crystalline phase was discussed in light of the results reported in the literature. Composite microparticles were obtained with a mean diameter ranging from 0.45 to 1.4 μm. An increase of about 4 times in the ABZ dissolution rate was measured for the particles with a 3:1 ABZ:β-cyclodextrin molar ratio with respect to the corresponding physical mixture and pure ABZ obtained by the same method. The dissolution improvement was attributed to the formation of the inclusion complex and a synergetic effect between both components, rather than the increase obtained for the change of ABZ to polymorphic form II.

Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process

This study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug in a one-step process. The chemotherapeutic agent docetaxel (DTX) is encapsulated with a block copolymer ELR containing the RGD peptide, a specific target sequence for cancer cells, using the supercritical anti-solvent (SAS) technique in a high process yield of up to 70%. SEM studies show spherical microparticles of 10μm after encapsulation. After dispersion under physiological conditions, microparticles disaggregate into stable monodisperse nanoparticles of 40nm size and −30mV ζ-potential. This protects the drug, as confirmed by NMR analysis, thereby increasing the water solubility of DTX up to fifty orders of magnitude. The delivery process is governed by the Fick diffusion mechanism and indicates that the presence of DTX on the particles surface is practically negligible. Cellular assays showed that, due to the presence of the cancer target sequence RGD, breast cancer cells were more affected than human endothelial cells, thus meaning that the strategy developed in this work opens the way to new controlled release systems more precise than non-selective chemotherapeutic drugs.

Supercritical Antisolvent Process for Pharmaceutical Applications: A Review

The supercritical antisolvent (SAS) technique has been widely employed in the biomedical field, including drug delivery, to obtain drug particles or polymer-based systems of nanometric or micrometric size. The primary purpose of producing SAS particles is to improve the treatment of different pathologies and to better the patient’s compliance. In this context, many active compounds have been micronized to enhance their dissolution rate and bioavailability. Aiming for more effective treatments with reduced side effects caused by drug overdose, the SAS polymer/active principle coprecipitation has mainly been proposed to offer an adequate drug release for specific therapy. The demand for new formulations with reduced side effects on the patient’s health is still growing; in this context, the SAS technique is a promising tool to solve existing issues in the biomedical field. This updated review on the use of the SAS process for clinical applications provides useful information about the achievements, the most effective polymeric carriers, and parameters, as well as future perspectives.

Supercritical antisolvent precipitation of calcium acetate from eggshells

The search for sustainable resources remains a matter of global interest. The presence of calcium in food waste may be a material to be valued. In this paper we show a new way of precipitating calcium acetate, produced from eggshells, using the supercritical antisolvent technique (SAS). It also presents the study of the precipitation efficiency as a function of the experimental conditions that affect the SAS results - temperature, pressure, liquid solution concentration and injection flow. It was possible to obtain good results under almost all experimental conditions, highlighting a higher yield for 200 bar pressures and lower solution injection flows. The obtained particles have a rod-like appearance having different sizes depending on the operating conditions.

Lowering the Operating Temperature of Perovskite Catalysts for N2O Decomposition through Control of Preparation Methods

Discovering catalysts that can decompose N2O at low temperatures represents a major challenge in modern catalysis. The effect of preparative route on N2O-decomposition activity has been examined for a PrBaCoO3 perovskite catalyst. Initially, a citric acid preparation was utilised where the A site ratio was altered in order to increase phase purity. Comparable compositions were then prepared by an oxalic acid precipitation method and by a supercritical anti-solvent technique to produce perovskites with a higher surface area (> 30 m2g-1). By altering the A site ratios it was possible to reduce the temperature required to produce a pure phase perovskite whilst maintaining a higher-surface area. The use of the different preparation methods resulted in perovskites with varying properties, as determined by N2 adsorption, XPS and O2-TPD. This work confirms the importance of lattice oxygen species that have high oxygen mobility for enhanced decomposition of N2O, as oxygen recombination is considered the rate-limiting step. Here, the formation of molecular oxygen is limited by surface adsorbed O species being within a distance at which oxygen recombination is possible. The most active PrBaCo-based catalyst did not have the highest percentage of lattice oxygen as shown by XPS, however, the catalytic activity could be correlated to the mobile oxygen species and high surface area. The PrBaCo-based catalyst prepared by supercritical anti-solvent converted 50 % of the N2O present in the feed (T50) at 410 °C, which represents a significant improvement over reported catalytic performance measured under similar conditions.

Fractionation and precipitation of licorice (Glycyrrhiza glabra L.) phytochemicals by supercritical antisolvent (SAS) technique

Supercritical anti-solvent precipitation (SAS) using carbon dioxide is a novel technique that can be used to produce powdered ingredients in small size particles, facilitating their incorporation into food matrices. In this work, the SAS precipitation of a licorice root ethanolic extract was studied. SAS assays were carried out at 15–20 MPa, 308.15 and 313.15 K, and two different concentrations (9.6 and 14.2 mg/ml) of the ethanolic licorice extract. In the range of conditions investigated, SAS pressure and temperature did not affect significantly the precipitation yield, but phytochemicals recovery was higher with the lower licorice extract concentration. Moreover, the fractionation of licorice bioactives (liquiritin, liquiritigenin, isoliquiritigenin, glabridin and glycyrrhizic acid) was assessed, together with the content of total phenolic compounds and antioxidant activity of the powders and oleoresin by-products obtained. In this respect, precipitates and oleoresins presented significant differences in the concentration of some licorice bioactives, and higher antioxidant activity was observed in precipitates. Additionally, significant effect of pressure, temperature and licorice extract concentration on the morphology and particle size of precipitates was observed, recovering smaller and more regular particles at 15–20 MPa, 313.15 K and 9.6 mg/ml licorice extract concentration, attaining satisfactory yield and antioxidant activity.

Solubility and modeling of telmisartan in binary solvent mixtures of dichloromethane and (methanol, ethanol, n-propanol, or n-butanol) and its application to the preparation of nanoparticles using the supercritical antisolvent technique

In this study, the mole-fraction solubility data for telmisartan in dichloromethane + primary alcohol (methanol, ethanol, n-propanol or n-butanol) mixtures were measured at five different temperatures by employing a solid-liquid equilibrium using the shake-flask technique. In addition, the melting temperature and enthalpy of telmisartan were determined by differential scanning calorimetry, while powder X-ray diffraction analysis was used to evaluate the crystal form of telmisartan obtained before and after the solubility experiments. The solid state characterization confirmed no transformation of telmisartan into polymorphs. The solvent synergistic effect was observed in all binary mixtures. In particular, the telmisartan solubility in the mass fraction values of dichloromethane (w) of 0.8 at 298.15 K was found to be approximately 90.77 and 4.98 times higher than that in pure methanol and pure dichloromethane, respectively. The experimental solubility data for telmisartan were correlated and fitted to the van't Hoff, modified Apelblat, simplified CNIBS/R-K, Jouyban-Acree, Jouyban-Acree-van't Hoff, Jouyban-Acree-Apelblat, Ma, and Sun models. The thermodynamic parameters, such as the dissolution enthalpy (∆H°), Gibbs free energy (∆G°), and dissolution entropy (∆S°), confirmed that the dissolution of telmisartan in the mixtures was an endothermic process. Furthermore, dichloromethane and primary alcohol mixtures (w = 0.8) were used as the solvent in the preparation of telmisartan nanoparticles using the supercritical antisolvent (SAS) technique. The smallest particle size (630.8 nm) of the telmisartan nanoparticle obtained from a solvent mixture of dichloromethane and methanol was obtained. Results confirmed that the solubility data and estimated equations for telmisartan in the dichloromethane + primary alcohol mixtures with a strong synergistic solvation are useful in research and development for the purification and preparation of nanoparticles as well as in future studies on telmisartan to design and develop dosage forms.

Supercritical anti-solvent process as an alternative technology for vitamin complex encapsulation using zein as wall material: Technical-economic evaluation

The objective of this study was to investigate the technical-economic feasibility of supercritical antisolvent (SAS) technique for the precipitation of a vitamin complex containing riboflavin, δ-tocopherol and β-carotenein zein microcapsules. First, the following parameters were investigated for the precipitation of pure zein: pressure (7.0–16.0 MPa), anti-solvent flow rate (20–60 g/min), solution flow ratio (0.5–1.5 mL/min) and concentration of zein in an aqueous ethanol solution (0.02–0.04 g/mL). Then, at optimized SAS condition for zein precipitation (pressure of 16 MPa, temperature of 313 K, zein concentration of 0.02 mg/mL, solution flow rate of 1 mL/min and anti-solvent flow rate of 60 g/min) was performed the co-precipitation of the vitamins with zein. The results showed that the mean particle size of the microcapsules varied from 8 to 18 μm, depending on the vitamins encapsulated, being its morphology spherical, meanwhile the precipitation yield was within the range of 41–82 g/100 g.

Production and Characterization of a New Copper(II) Propanoate-Isonicotinamide Adduct Obtained via Slow Evaporation and using Supercritical CO2 as an Antisolvent

A new adduct of isonicotinamide (INA) with copper(II) propanoate [Cu(C3)2] was prepared [Cu2(C3)4(INA)4] using two different methods. This type of compound shows high fungicidal activity. Solvent evaporation from ethanol rendered crystals suitable for single-crystal X-ray diffraction. Furthermore, a new semicontinuous method capable of simultaneous crystallization and micronization of the adduct using supercritical CO2, the supercritical antisolvent technique (SAS), was also assessed. Crystals were characterized using powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis coupled with mass spectrometry, scanning electron microscopy, and microelemental analysis. In the adduct, two copper(II) ions are coordinated through two bridging and two chelating carboxylates to the propanoate anions forming approximately a plane. Each metal ion is then coordinated with the pyridine nitrogen of two different INA molecules that behave as monodentate ligands. The amide groups of the INA form H-bonds with other amide and carboxylate groups forming a molecular crystal with a three-dimensional H-bond arrangement of the binuclear units. With the SAS technique, crystals 100-fold smaller than those obtained by slow evaporation were obtained, proving SAS as a suitable method for mixed-ligand complexes preparation with reduced particle size and therefore expected bioavailability enhancement.