Antisolvent Technique Research Articles

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.

Pickering high internal phase emulsions with excellent UV protection property stabilized by Spirulina protein isolate nanoparticles

Herein, we reported the use of natural, renewable, and food-grade Spirulina protein isolate nanoparticles (SPI NPs) as effective particle stabilizers for Pickering high internal phase emulsions (Pickering-HIPEs). SPI NPs were prepared using a straightforward antisolvent technique and characterized using dynamic light scattering (DLS), and zeta potential measurement as well as scanning electron microscopy (SEM). SPI NPs were afterward used as sole stabilizers to prepare the oil-in-water (O/W) HIPEs, the effects of oil content, particle concentration, and pH of aqueous phase on the microstructure, stability, and rheological behaviors of the resulting Pickering-HIPEs were investigated. The Pickering-HIPEs generated showed a self-supporting gel network, a high oil content (up to 85 vol%), and extraordinary storage stability after prolonged storage and UV exposure. Concurrently, the Pickering-HIPEs provided good UV protection for a variety of photosensitive compounds, including β-carotene, vitamin E, and limonene. These findings would not only advance the development of biocompatible particle stabilizers for Pickering-HIPEs in cosmetic, food, and pharmaceutical industries, but they would also provide a guidance for the protection of photosensitive compounds.

CO2 utilization as gas antisolvent for the pharmaceutical micro and nanoparticle production: A review

A reduction in particle size improves the solubility and bioavailability of pharmaceuticals. The traditional methods utilized in this regard are associated with problems so the use of supercritical fluid has been highlighted in recent decades. To prepare nanoparticles by employing the gas antisolvent (GAS) technique, a specific amount of solution (solute dissolved in organic solvent) was loaded into a cell in the oven. The supercritical carbon dioxide was injected and dissolved into the organic solvent. Therefore, volume expansion occurred and the solute was precipitated with a new particle size distribution on the filter at the end of the cell. This technique exhibits advantages such as particle size control, solvent-free product, and low-temperature process. Many experimental and modeling research has been conducted to synthesize nano- and microparticles based on the GAS process. The present study seeks to review the effective factors and literature on the GAS technique. All parameters affecting the GAS process including pressure, temperature, antisolvent addition rate, initial soluble concentration, and solvent were investigated. Volume expansion, thermodynamic modeling, and kinetic modeling of the GAS process were reviewed. A comparison was conducted between the advantages and disadvantages of this method with other methods of producing nanoparticles with supercritical fluid.

Performance of planar perovskite solar cells based on formamidinium cations: Simulation and fabrication

The best efficiency ever recorded for state-of-the-art perovskite solar cells (PSCs) is about 25% where the formamidinium (FA)-dominated perovskites were adopted. But the optimum content of FA perovskite solar cells based on Cs0.05(FAxMA[1−x])0.95Pb(I0.83Br0.17)3 films has yet to materialize the high-power conversion efficiency. Herein, high quality and uniform perovskite films constituting Cs-MA-FA (Cesium; Methylammonium) mixed cation in the A-site of the ABX3 structure with different FA content are synthesized by a typical spin coating based antisolvent technique. Because of the limitations of perovskite and solar cell materials, the influences of various FAs on the device performance are analyzed through device simulation. From the synthesized films, the band gap equation of Cs0.05(FAxMA[1−x])0.95Pb(I0.83Br0.17)3 has been estimated, ranging from 2.175 eV to 1.5 eV for various FA/(FA + MA) ratios respectively. Ultimately, the highest conversion efficiency of the planar solar cell based on graded perovskite with various FA content was obtained for the case where the positive Eg grading consists of the Eg of 2.175 eV at the front (FA/[FA + MA] of 0) and the Eg of 1.5 eV at the back (FA/[FA + MA] of 1). The Cs0.05(FA0.87MA0.13)0.95Pb(I0.83Br0.17)3 cell achieved an AM1.5G conversion efficiency of around 20.98%, showing improved VOC, JSC, and FF among the planar perovskite solar cells with different x.

Biodegradable Polymers-Based Smart Nanocrystals for Loxoprofen Delivery with Enhanced Solubility: Design, Fabrication and Physical Characterizations.

Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.

Supercritical Antisolvent Technique for the Production of Breathable Naringin Powder.

Flavonoids are polyphenolic compounds largely present in fruits and vegetables possessing antioxidant properties, anti-inflammatory and antibacterial activities. Their use in clinical practice is very poor due to their low bioavailability, susceptibility to oxidation and degradation. Moreover, their slight solubility in biological fluids and a consequent low dissolution rate leads to an irregular absorption from solid dosage forms, even though, anti-inflammatory formulations could be used as support for several disease treatment, i.e. the COVID-19 syndrome. To improve flavonoid bioavailability particle size of the powder can be reduced to make it breathable and to promote the absorption in the lung tissues. Supercritical fluid based antisolvent technique has been used to produce naringin particles, with size, shape and density as well as free flowing properties able to fit inhalation needs. The dried particles are produced with the removal of the solvent at lower temperatures compared to the most used traditional micronization processes, such as spray drying. The best breathable fraction for naringin particles is obtained for particles with a d50~7 µm manufactured at 35 °C-150 bar and at 60 °C-130 bar, corresponding to 32.6% and 36.7% respectively. The powder is produced using a high CO2 molar fraction (0.99) that assure a better removal of the solvent. NuLi-1 cell line of immortalised bronchial epithelial cells adopted to evaluate powder cytotoxicity indicated after 24 h absence of toxicity at concentration of 25 µM.

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.

Kinetic Study and Thermal Decomposition Mechanisms of Superthermite–Based Nitrocellulose Nanocomposite

ABSTRACT As ferric oxide is a well-known catalyst, aluminum can act as a high energy dense material. Ferric oxide/aluminum can experience nanothermite reaction with novel synergistic characteristics. On the other hand, nitrocellulose (NC) is the most energetic polymeric matrix. This study reports on the facile development of thermite-based NC nanocomposite. Ferric oxide nanoparticles (NPs) of 5 nm size and aluminum NPs of 80 nm size were dispersed in acetone. Colloidal ferric oxide/aluminum NPs were integrated into NC matrix via anti-solvent technique. Nanothermite particles offered an increase in NC decomposition enthalpy by 38.59% using differential scanning calorimetry (DSC). The apparent activation energy of NC was reduced by 14% and 14.5%, using Friedman and OZAW models, respectively. Activation energy at different conversion extent was evaluated, and decomposition mechanisms have been suggested to be heterogeneous solid phase reaction. The developed NC nanocomposite is considered bespoke material for first-fire ignition systems; where molten solid particle and high decomposition enthalpy are highly appreciated.

Enhanced aqueous dissolution of hydrophobic apixaban via direct incorporation of hydrophilic nanographene oxide

In this study, we have directly incorporated nanographene oxide (nGO) into a hydrophobic drug for enhanced dissolution performance through an antisolvent technique. Apixaban (APX) drug composites were synthesized with nGO incorporation ranging from 0.8% to 2.0% concentration. It was observed that the nGO was successfully embedded without any changes to the original drug crystal structure or physical properties. Dissolution of the drug composites was evaluated using US Pharmacopeia Paddle Method (USP 42). The time needed to reach a 50% release (T50) reduced from 106 min to 24 min with the integration of 1.96% nGO in APX and the T80 also dropped accordingly. Alternatively, dissolution rate showed promising performance with increase in nGO concentration. Initial dissolution rate increased dramatically from 74 µg/min to 540 µg/min. Further, work done in intestinal media revealed T50 went from not dissolving to 79.0 min. Decreased lipophilicity or logP value and increased aqueous solubility are both accredited to hydrophilic nGO water dispersion, producing a hydrophilic channel into the drug crystal surfaces through intermolecular interaction. Additionally, physical, and chemical characterizations confirm that hydrophobic apixaban was successfully transformed into a hydrophilic composite, showing potential for this technology to improve dissolution rate of a model hydrophobic compound.

Formulation and Characterization of Phytophospholipid Complex of Andrographis Paniculata Extract

Active constituents extracted from various parts of the plants have wide therapeutic potential for the treatment of diseases. Number of these compounds obtained elicits positive in vitro pharmacological effect; however poor in vivo absorption of polyphenolic compounds limited the widespread applicability. One of the novel strategies to improve the bioavailability and thereby oral absorption of these compounds is the use of phytophospholipid complexes. The present work is aimed to formulate and characterize phytophospholipid complex of methanolic extract of leaves of Andrographis paniculata by anti-solvent precipitation technique. Four different formulation batches (F1-F4) were prepared by combining the phospholipid and Andrographis paniculata leaves extract in different molar ratios. Formulated batches were characterized for particle size, polydispersity index, entrapment efficiency, FTIR, SEM, XRD, and in vitro drug release characteristic. On the basis of various experimental resulted the formulation batch (F4) with molar ratio of extract and phospholipids 1:2 was found to be stable giving highest drug loading and sustained drug release for prolonged period of time.

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.

Enhancement of Curcuma xanthorrhiza Roxb Phytochemical Dissolution via Micronization Using a Supercritical Antisolvent Technique.

Fine particles comprising Curcuma xanthorrhiza Roxb (C. xanthorrhiza) rhizome extract were successfully generated using a supercritical carbon dioxide (SCCO2) antisolvent technique. The SCCO2 antisolvent process was performed at 40 °C with 8–16 MPa operating pressures. The CO2 and feed solution flow rates were 15 and 0.25 mL min–1, respectively. The mixture of C. xanthorrhiza rhizome extract and a polyvinylpyrrolidone (PVP) polymer in acetone–ethanol was used as a feed solution. The collected particle products seemed to possess spherical and spherical-like morphologies with a diameter of less than 500 nm. The infrared spectroscopy analysis showed that the structural properties of C. xanthorrhiza rhizome extract did not change after treatment with the SCCO2 antisolvent. Furthermore, the addition of the PVP polymer in the C. xanthorrhiza rhizome extract particle products may improve their dissolution significantly in an aqueous solution medium.

Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

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.

Pickering Emulsions and Antibubbles Stabilized by PLA/PLGA Nanoparticles.

Micrometer-sized double emulsions and antibubbles were produced and stabilized via the Pickering mechanism by colloidal interfacial layers of polymeric nanoparticles (NPs). Two types of nanoparticles, consisting either of polylactic acid (PLA) or polylactic-co-glycolic acid (PLGA), were synthesized by the antisolvent technique without requiring any surfactant. PLA nanoparticles were able to stabilize water-in-oil (W/O) emulsions only after tuning the hydrophobicity by means of a thermal treatment. A water-in-oil-in-water (W/O/W) emulsion was realized by emulsifying the previous W/O emulsion in a continuous water phase containing hydrophilic PLGA nanoparticles. Both inner and outer water phases contained a sugar capable of forming a glassy phase, while the oil was crystallizable upon freezing. Freeze drying the double emulsion allowed removing the oil and water and replacing them with air without losing the three-dimensional (3D) structure of the original emulsion owing to the sugar glassy phase. Reconstitution of the freeze-dried double emulsion in water yielded a dispersion of antibubbles, i.e., micrometric bubbles containing aqueous droplets, with the interfaces of the antibubbles being stabilized by a layer of adsorbed polymeric nanoparticles. Remarkably, it was possible to achieve controlled release of a flourescent probe (calcein) from the antibubbles through heating to 37 °C leading to bursting of the antibubbles.

Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of solubility and dissolution rate

Nimodipine (NMD) is a dihydropyridine calcium channel blocker useful for the prevention and treatment of delayed ischemic effects. It belongs to class ? drugs, which is characterized by low solubility and high permeability. This research aimed to prepare Nimodipine nanoparticles (NMD NPs) for the enhancement of solubility and dissolution rate. The formulation of nanoparticles was done by the solvent anti-solvent technique using either magnetic stirrer or bath sonicator for maintaining the motion of the antisolvent phase. Five different stabilizers were used to prepare NMD NPs( TPGS, Soluplus®, HPMC E5, PVP K90, and poloxamer 407). The selected formula F2, in which Soluplus 
 has been utilized as a stabilizer, has a particle size (77 nm) and polydispersity index (PDI) (0.016). The formulas with the smallest particle size were freeze dried with the addition of 1 % w/w mannitol as cryoprotectant. The saturation solubility of NMD in the prepared nanoparticles was increased twenty four-folds, and the complete dissolution was achieved at 90 minutes compared with pure NMD, which reaches only 6%. The formation of hydrogen bonding between NMD and the polymer or the cryoprotectant, as confirmed by the FTIR study. In conclusion, the preparation of NMD as polymeric nanoparticles is a useful technique for enhancing the solubility and dissolution rate.

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.

Simvastatin nanosuspensions prepared using a combination of pH-sensitive and timed-release approaches for potential treatment of colorectal cancer

A dual pH- and time-dependent polymeric coated capsule was developed to achieve the site specificity of simvastatin (SIM) release in the colon. To improve the SIM solubility, soluplus-based nanosuspension of the drug were prepared by applying the anti-solvent crystallization technique; this was then followed by lyophilization. Particle size, polydispersity index, and saturation solubility were evaluated. The optimized nanosuspension was combined with SLS and freeze-dried before filling into hard gelatin capsules. Drug release characteristics of the coated capsules were studied in HCl 0.1 N, the phosphate buffers 6.8 and 7.4, and the simulated colonic fluid (pH 6.8). The in-vitro cytotoxic effects of SIM nanoparticles against HT29 cells were then evaluated using the MTT assay. The prepared nanoparticles were spherical with a mean size of 261.66 nm, the zeta potential of −18.20 and the dissolution efficiency of 59.71%. X-ray diffraction and differential scanning calorimetry studies showed that the nanosizing technique transformed the crystalline drug into the more soluble amorphous form. The coated capsules had no release in the gastric media, providing the specific delivery of SIM in the colon. The cytotoxic effect of the SIM nanoparticles was significantly increased, as compared to the free SIM. The findings, therefore, showed that the coated capsules using the two polymers of ethyl cellulose and Eudragit S100 could be suitable for the colon target delivery of SIM.

Encapsulation of trans-resveratrol in poly(ε-caprolactone) by GAS antisolvent

In this study, poly(ε-caprolactone) particles containing resveratrol were developed employing the GAS antisolvent technique. A central composite design 22 evaluated the influence of polymer, resveratrol mass ratio (2:1, 1:1, 1:2), and pressure (100, 120, 140 bar) on encapsulation percentage, and efficiency. The values obtained for encapsulation efficiency and percentage of encapsulation at the best conditions attained were 99.34% and 65.31%. In addition, the statistical analysis showed that only the mass ratio had significantly affected the percentage of encapsulation, but neither variable significantly affected efficiency. Microparticles produced demonstrably heterogeneous characteristics and irregular morphology. However, this process did not change either the compound chemical structures or the resveratrol antioxidant activity. Microparticles maintained constant release for 48 h, and in thermal oxidative analysis, the difference between samples and control was 2.57 times smaller than the difference between pure resveratrol and the control sample.

Precipitation of quercetin and nicotinamide in carbon dioxide + ethanol systems at high pressures: Phase equilibrium data for antisolvent processes

The dataset obtained in this work comprise original new data on the phase equilibrium of ternary systems CO2 + ethanol + quercetin (QCN), CO2 + ethanol + nicotinamide (NIC), and the quaternary system CO2 + ethanol + QCN + NIC with a molar ratio of 1:1 (QCN:NIC), which comprehension of phase behavior can be useful to establish experimental conditions for further co-precipitation, co-crystallization or related particle-obtaining processes with QCN and/or NIC at elevated pressures by antisolvent techniques. The data were obtained with the synthetic-visual method at temperatures of 308.15, 318.15, and 328.15 K and pressures up to 10.17 MPa. The vapor-liquid equilibrium (VLE) with or without the presence of a solid phase (VLSE) was observed for all systems evaluated. For ternary systems, VLSE occurred at all temperatures from CO2 molar fractions between 0.7625 and 0.8499 for QCN, and close to 0.9 for NIC, at solid concentrations ranging from 0.02 to 0.06 %mol of solute in ethanol. Solid presence did not considerably alter the binary VLE behavior of solvent/antisolvent mixtures in terms of transition pressures, and the Peng-Robinson equation of state (PR-EoS) fitted well to the data considering systems as pseudobinaries.