Supercritical Solvent Research Articles

Preparation of ROS-responsive drug-loaded hydrogels applied in wound dressings using supercritical solvent impregnation

Drug-loaded hydrogels with wound environment stimuli-responsive property can significantly promote wound healing and are widely applied in dressings. Two natural polymers, i.e. sodium alginate and sodium hyaluronate, were modified by 3-aminophenylboric acid and then cross-linked with polyvinyl alcohol to prepare ROS responsive hydrogels. Doxycycline hydrochloride was loaded onto hydrogels using supercritical solvent impregnation (SSI) technology, and the effects of immersion time, pressure and temperature on drug loading capacity (DLC) were investigated. DLC firstly increased and then decreased with the elevation of supercritical CO2 pressure, and maximum value was up to 11 mg/g at 15 MPa and 50 °C. In the in vitro drug release study, doxycycline hydrochloride was controllably released from hydrogels for 10 h via the sensitivity of boronate ester bonds to ROS. This work expands the application of SSI in wound dressing, which provides a new approach for the design of composite hydrogel formulations with uniform drug distribution.

Supercritical impregnation of chitosan sponges with 17β-estradiol

Chitosan sponges with open porous structures have great potential as drug delivery matrices for constructing transdermal patches. Supercritical solvent impregnation (SSI) is an advantageous green technique for the inclusion of hydrophobic drugs into porous matrices. In this work SSI of chitosan sponges with 17β-estradiol (E2) using a supercritical scCO2 /ethanol medium under static conditions was investigated. In the SSI study, the influence of such operating parameters as temperature (35 and 65 °C), pressure (15–120 MPa, which corresponds to density of CO2 815–1142 kg m-3.), and a molar fraction of the drug (from 2.3 ×10-3 mol% to 8.9 ×10-3 mol% from CO2 amount) in the reactor on the loading capacity and the efficiency of the uptake was evaluated. It was revealed that hormone loading increased linearly with the initial concentration of E2 and CO2 density in the reactor. The developed processing parameters for SSI made it possible to vary the loading of E2 into the chitosan sponges in a wide range from a few to hundreds of µg per mg of the matrix, which corresponds to the adequate doses range of the hormone used in transdermal delivery. The successful inclusion of E2 into the polymer matrices was proven by UV spectroscopy, powder X-ray diffraction, fluorescence microscopy, and scanning electron microscopy. It was found that SSI method provides a strong micronization and a uniform distribution of E2 crystallites in the sponge volume, which may positively affect the bioavailability of the drug.

Optimization of Heat Exchanger Operation at Supercritical Solvent Regeneration Unit of Heavy Resid Deasphalting Plant

Optimization of Heat Exchanger Operation at Supercritical Solvent Regeneration Unit of Heavy Resid Deasphalting Plant

Synthesis of cyclic polystyrene in supercritical carbon dioxide green solvent

This study presents the synthesis of cyclic polystyrene (cPS) in the supercritical carbon dioxide (SC-CO2) media for the first time. For this purpose, first of all α−ω difunctionalized polystyrene was prepared in the SC-CO2 solvent within the pressure range from 100 to 230 bar and at a temperature below the conventional methods 80℃. The end-to-end reaction method was then used to make cPS in SC-CO2 solvent with CH2Cl2 as a co-solvent. The effects of several factors such as pressure, time, and initiator concentration on polymer yield, morphology, and molecular weight were studied. FTIR,1H NMR, GPC, HPLC, DSC, TGA and SEM analyses were used to characterize the product and evaluate the effect of mentioned factors. The results indicated a prominent influence of SC-CO2 pressure on the product. Applying a green solvent, such as SC-CO2 allows us to produce a clean polymer with lower molecular weight and higher environmental compatibility.

Experimental study of ketoconazole impregnation into polyvinyl pyrrolidone and hydroxyl propyl methyl cellulose using supercritical carbon dioxide: Process optimization

This study aims to increase the oral bioavailability of ketoconazole (KET, drug) by incorporating it into water-soluble polymers, using supercritical carbon dioxide (SC-CO2) as the impregnating solvent. For this purpose, loading of KET into poly (vinylpyrrolidone) (PVP) and hydroxy propyl methyl cellulose (HPMC) using supercritical solvent impregnation (SSI) was investigated for the first time. Box-Behnken design (BBD) was used to optimize the impregnation process. Effects of three process parameters, namely pressure (150, 200 and 250 bar), impregnation time (60, 120 and 180 min), and temperature (308, 318 and 328 K) on the loading were studied, leading to a range of 0.33%− 0.98% for KET into PVP and 0.46%− 1.41% for KET into HPMC polymer. Samples were examined using FTIR, DLS, SEM, XRD and DSC analyses. Additionally, the small particle size and the presence of polymers increased the dissolution rate of the drug in aqueous solutions up to 7.3 folds.

Design of volatile organic compounds profiles of roasted Coffea arabica extracts produced by supercritical and conventional solvents

SummaryThis work addresses the potential of supercritical fluid extraction (SFE) to design volatile organic compounds (VOCs) profiles using roasted Coffea arabica. On the whole, 57 VOCs were identified by HS‐SPME/GC–MS. A full factorial design was adopted to study the effect of pressure (180 and 300 bar), temperature (40 and 80 °C) and ethanol content (0 and 5 wt.%). The total extraction yield ranged from 1.4 wt.% to 9.8 wt.%. At 180 bar and 80 °C, two extracts exhibited VOCs amount up to 3.5 times higher than the dichloromethane extract. Temperature and pressure favoured VOCs amount and total yield in conflicting ways, and ethanol had a negligible effect on VOCs amount. At 180 bar and 80 °C, the VOCs profile revealed a reinforcement of pyrroles, phenols, cyclopentenes and pyrans, at the expense of pyridines, carboxylic acids and furans. Hence, this essay evidences the potential of SFE to engineer coffee VOCs profiles.

Supercritical Extraction of a Natural Pyrethrin-Rich Extract from Chrysanthemum Cinerariifolium Flowers to Be Impregnated into Polypropylene Films Intended for Agriculture Applications

The extensive use of synthetic pesticides and their addition to the field presents significant environmental problems that must be minimized. The use of natural insecticides and their addition using techniques that minimize their impact in the field are widely studied by the current scientific community. In this work an extraction method based on supercritical CO2 to obtain a pyrethrin-rich natural extract from different varieties of chrysanthemum flowers is analyzed. This extract would be used in a supercritical solvent impregnation (SSI) process to produce a commercial polypropylene (PP) film with insecticidal properties to be used in greenhouses. The extract selected for the impregnation process was that obtained from the Atlantis variety at 35 °C and 10 MPa pressure. The amount of insecticide impregnated into the polymer at 55 °C and under two different pressure levels (10 MPa and 40 MPa) have been determined. A batch impregnation method (BM) with 5 h constant impregnation time and low depressurization rates were used to favor the impregnation process. The results demonstrated that this procedure was suitable to produce pyrethrin-loaded PP films that could to be used in greenhouses as a protection against pests, while allowing a more rational and moderate use of other chemical pesticides.

A sustainable approach for material and metal recovery from E-waste using subcritical to supercritical methanol

The heterogeneous nature of e-waste, which is a rich source of metals, polymers, glass fibres and ceramics, is troublesome. Multi-step processes are employed to effectively treat e-waste with minimum environmental impact. In this research, a subcritical to supercritical methanol environment was investigated to pre-treat e-waste, recovering non-metallic fractions and eventually concentrate metals from e-waste. Experiments were conducted in the temperature range of 150 °C to 300 °C at an autogenous pressure with initial atmospheric pressure. The mechanism of depolymerization was investigated by varying reaction time from 30 min to 240 min; solid to liquid ratio of 1:10 to 1:30 g/ml in a batch reactor under N2 environment. Comparative analysis of liquid products obtained after Supercritical Methanol (SCM) treatment for both Waste Random Access Memory (WRAM) and Waste Printed Circuit Board (WPCB) was done with pyrolyzed oil/liquid product. This research briefly illustrates oil and solid product compositional changes with operating temperature, pressure, and solid/liquid ratio range. The metal concentrations of copper, nickel, silver, zinc, and gold are greater than 90% after SCM treatment. For comparison, the feed material was pyrolyzed under the same condition, the difference in oil and solid products are assessed. In the end section, the environmental and economic benefits of SCM were also discussed compared to other supercritical and conventional technologies. An efficient and greener approach of supercritical solvent is proposed via this research for e-waste recycling.

Development and validation of machine learning models for prediction of nanomedicine solubility in supercritical solvent for advanced pharmaceutical manufacturing

Salsalate solubility in supercritical carbon dioxide was studied in this research by computational simulation to correlate the solubility to input parameters including temperature and pressure. A dataset was collected from resources and the models were correlated to the data. Both training and validation steps have been performed to implement the computational tasks. Indeed, we are dealing with a dataset with two P and T inputs and one output (drug solubility), and 32 data points. We chose three models based on Gaussian Process Regression (GPR) including simple (raw) GPR, Ada-boosted GPR, and Bagged GPR as two ensemble methods for correlation of the solubility data. All hyper-parameters were tuned for more general models and models evaluated with standard metrics. The GPR, Adaboost + GPR, and Bagging + GPR have scores of 0.9779, 0.9992, and 0.9795 using R-squared, respectively. Also, in terms of RMSE models have error rates of 1.25 × 10−4, 1.20 × 10−4, and 1.29 × 10−4, respectively. Finally, considering the standard criteria and visual analysis, the boosted GPR model is selected as the main model. The optimal values found as (P = 400, T = 338.0, Y = 0.003879).

Nanoparticle Production of Zingiber officinale Roscoe Rhizome Extracts by ESS (Expansion of Supercritical Solution)

Aims: To propose a modified RESS method of herbal pharmaceutical extracts nanoparticle production. Background: A vast number of methods have been applied to water-insoluble pharmaceuticals to improve their solubility. Nanoparticle production of pharmaceuticals is considered as one of the high-speed ways to improve solubility. Objective: Supercritical CO2 was applied to extract Zingiber officinale Roscoe rhizome pharmaceutical. Then, a modified RESS (Rapid Expansion of Supercritical Solution) method, called ESS (Expansion of Supercritical Solution), was exerted to obtain NPs (nanoparticles) of the extracted pharmaceuticals. Methods: Initially, applying high pressure in supercritical CO2 contributed to the extract dissolution such that supercritical CO2 was saturated with the sample. Then, by decreasing the pressure, an expansion occurred in the saturated medium. This expansion reduced the power of supercritical CO2 solvent and induced the sample nanoparticle nucleation in the needle valve. Results: LC-MS (Liquid Chromatography-Mass Spectrometry) and EDX (energy dispersive X-ray spectroscopy) result provided solid evidence for the presence of anti-cancer pharmaceutical, [6]-Gingerol, in the extract. The medium size of the nanoparticles in FESEM (Field Emission Scanning Electron Microscopy) analysis was 36 nm. The most satisfactory parameters for a 2 mg mL-1 feeding solution were the initial pressure of 350 atm, secondary pressure of 160 atm, equilibrating time of 10 min, precipitating time of 20 min, and temperature of 48 °C. Conclusion: Unlike rapid expansion of supercritical solution methodology, in this technique, the initial and secondary pressures were permanently above the critical pressure to provide a gentle expansion, which contributes to the production of uniform and small particles. The obtained uniform NPs had a narrow size distribution. Consequently, ESS technique can be considered as an efficient technique for improving the solubility of hydrophobic pharmaceuticals, such as [6]-gingerol.

Supercritical CO2 impregnation approach for enhancing dissolution of fenofibrate by adsorption onto high-surface area carriers

Hydrophobic drugs pose a challenge to pharmaceutical oral dosage forms because their low dissolution reduced bioavailability. In this study, we developed different strategies to adsorb fenofibrate (FB), a BCS II drug, onto high-surface-area carriers (Ae200) to enhance its dissolution. As compared to physical mixing and spray drying, physical adsorption and supercritical fluid methods showed the highest dissolution rates (over 80% in 30 min and over 90% in 60 min) with the highest surface area values. Among the two best methods, supercritical solvent impregnation technique (SCF1) offered better dissolution behavior, attributed to the FB physical state transition from crystalline to amorphous. This improvement suggests the potential of the SCF1 in the development of hydrophobic drugs.

Computational prediction of drug solubility in supercritical carbon dioxide: Thermodynamic and artificial intelligence modeling

In this study, machine learning (ML) computations were carried out for description of drug solubility in supercritical carbon dioxide. Supercritical solvent has been used in this work due to its superior properties and high solvation capacity for drug dissolution. The model has been developed and tested for salsalate as well as decitabine drugs, and their solubility at various pressures and temperatures were predicted using the developed machine learning model. The models were developed by taking into account the pressure between 120 and 400 bar, and temperature between 308 and 338 K for understanding the influence of pressure and temperature on salsalate and decitabine drug dissolution in the solvent. Moreover, the model’s accuracy was compared with some empirical correlations from previous studies. It was indicated that the ML model had better accuracy compared to the semi-empirical correlations. The pressure was indicated to have considerable influence on the solubility variations for both drugs. The best thermodynamic model showed the least average absolute relative deviation percent of around 8 % for the whole data points for salsalate. For development of machine learning model, artificial neural network was trained using the measured data. The neural network was developed using one hidden layer, two inputs, and one output. Pressure and temperature were taken as inputs for the network, and the solubility of drug as the predicted output in the neural network. The training and validation of the neural network using salsalate and decitabine solubility indicated great accuracy with coefficient of determination higher than 0.99 for both steps.

Thermodynamic modeling of pharmaceuticals solubility in pure, mixed and supercritical solvents

In this study, the capability of the PHSC model was evaluated to predict the solubility of the pharmaceuticals in pure, mixed, and supercritical solvents over a wide range of temperatures and pressures. The PHSC model was utilized for fifteen pharmaceutical compounds in pure and mixed solvents. The prediction results of the PHSC model were compared to PC-SAFT, COSMO-RS, and COSMO-SAC models. Twenty-one ternary systems were considered to study the solubility of pharmaceuticals in the mixed solvents. Finally, the solubility of five pharmaceuticals in supercritical CO2 at different temperatures was estimated using an adjustable temperature-dependent binary interaction parameter. The obtained results show that the solubility of pharmaceuticals in different solvents and supercritical CO2 can be estimated using the PHSC model satisfactory.

Production of Oil and Phenolic-Rich Extracts from Mauritia flexuosa L.f. Using Sequential Supercritical and Conventional Solvent Extraction: Experimental and Economic Evaluation

Mauritia flexuosa L.f. is a palm from the Amazon. Pulp and oil are extracted from its fruits, with a high content of bioactive compounds. This study presents the economic evaluation of two extraction processes: (a) Conventional solvent extraction (CSE) with 80% ethanol for the recovery of phenolic-rich extracts; and (b) Supercritical fluid extraction (SFE) followed by CSE to obtain oil and phenolic-rich extracts. The objective of this study was to compare the feasibility of both extraction processes. The economic evaluation and the sensitivity study were evaluated using the SuperPro Designer 9.0® software at an extraction volume of 2000 L. Similar global extraction yields were obtained for both processes; however, 8.4 and 2.4 times more total polyphenol and flavonoid content were extracted, respectively, using SFE+CSE. Cost of manufacturing (COM) was higher in SFE+CSE compared to CSE, USD 193.38/kg and USD 126.47/kg, respectively; however, in the first process, two by-products were obtained. The sensitivity study showed that the cost of the raw material was the factor that had the highest impact on COM in both extraction processes. SFE+CSE was the most economically viable process for obtaining bioactive compounds on an industrial scale from M. flexuosa L.f.

One-Step Grown Carbonaceous Germanium Nanowires and Their Application as Highly Efficient Lithium-Ion Battery Anodes.

Developing a simple, cheap, and scalable synthetic method for the fabrication of functional nanomaterials is crucial. Carbon-based nanowire nanocomposites could play a key role in integrating group IV semiconducting nanomaterials as anodes into Li-ion batteries. Here, we report a very simple, one-pot solvothermal-like growth of carbonaceous germanium (C-Ge) nanowires in a supercritical solvent. C-Ge nanowires are grown just by heating (380–490 °C) a commercially sourced Ge precursor, diphenylgermane (DPG), in supercritical toluene, without any external catalysts or surfactants. The self-seeded nanowires are highly crystalline and very thin, with an average diameter between 11 and 19 nm. The amorphous carbonaceous layer coating on Ge nanowires is formed from the polymerization and condensation of light carbon compounds generated from the decomposition of DPG during the growth process. These carbonaceous Ge nanowires demonstrate impressive electrochemical performance as an anode material for Li-ion batteries with high specific charge values (>1200 mAh g–1 after 500 cycles), greater than most of the previously reported for other “binder-free” Ge nanowire anode materials, and exceptionally stable capacity retention. The high specific charge values and impressively stable capacity are due to the unique morphology and composition of the nanowires.

In-plane defect engineering on MoS2 through a novel two-phase hydrothermal synthesis

In this work, we proposed a two-phase hydrothermal synthesis approach to fabricate high-curvature bulk surface with engineered in-plane defects. Organic or supercritical solvents were introduced as a second immiscible media to alter MoS2 hydrothermal growth. Two mixing scenarios, depending on the ratio of organic solvent to aqueous solution. In the case of the organic solvent isolated by aqueous solution, the growing slabs change its original direction when getting contact with the organic droplets. In the scenario that aqueous droplets dispersed in organic solvent, MoS2 slabs grow along the curved interfaces of aqueous droplets. Experimental results showed that the curved basal planes were generated in the two cases and more curvatures were introduced in the second phase under adequate mixing energy. Higher curvature degree led to a better catalytic performance. Compared to decalin, supercritical heptane that can facilitate the dispersion of the precursor-containing aqueous solution into homogeneous nano-size reaction cells, showed a great capacity to generate highly curved slabs. MoS2 synthesized with supercritical solvent exhibits the highest activity among the investigated catalysts. The catalysts were characterized by SEM, XRD, XAFS, TPR and nitrogen adsorption analysis. The results were proved by the theoretical calculations that the formation energy (Eform) of sulfur vacancy (VS) on curly structure possesses a reduction of 0.19 eV comparing with planar MoS2 monolayer. The curved structure can facilitate the surface VS generation by depopulating the occupied bonding states of corresponding Mo-S bonds. This work provides an effective approach to create basal defects on the MoS2 to promote its catalyst activity.

Curcumin and n-acetylcysteine cocrystal produced with supercritical solvent: characterization, solubility, and preclinical evaluation of antinociceptive and anti-inflammatory activities.

Curcumin presents a promising anti-inflammatory potential, but its low water-solubility and bioavailability hinder its application. In this sense, cocrystallization represents a tool for improving physicochemical properties, solubility, permeability, and bioavailability of new drug candidates. Thus, the aim of this work was to produce curcumin cocrystals (with n-acetylcysteine as coformer, which possesses anti-inflammatory and antioxidant activities), by the anti-solvent gas technique using supercritical carbon dioxide, and to test its antinociceptive and anti-inflammatory potential. The cocrystal was characterized by differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy. The cocrystal solubility and antichemotaxic activity were also assessed in vitro. Antinociceptive and anti-inflammatory activities were carried out in vivo using the acetic acid-induced abdominal writhing and carrageenan-induced paw oedema assays in mice. The results demonstrated the formation of a new crystalline structure, thereby confirming the successful formation of the cocrystal. The higher solubility of the cocrystal compared to pure curcumin was verified in acidic and neutral pH, and the cocrystal inhibited the chemotaxis of neutrophils in vitro. In vivo assays showed that cocrystal presents increased antinociceptive and anti-inflammatory potency when compared to pure curcumin, which could be related to an improvement in its bioavailability.

Formation of Curcuma xanthorrhiza extract microparticles using supercritical anti solvent precipitation

Curcuma xanthorriza (C. xanthorrizha) is one of the most medicinal plant used in pharmacy and have many scientifically proven health benefits. In this work, C. xanthorrhiza extract was used as starting material to form microparticles. To prevent the rapid oxidation and to enhance stability, bioavailability, and solubility in water, C. xanthorrhiza extract was combined with polyvinylpyrrolidone (PVP) to form microparticles using supercritical anti solvent (SAS) precipitation. Acetone was used as solvent while supercritical CO2 was used as the antisolvent. The effects of pressure and extract-PVP ratio on the particle size and morphology of particles formed were evaluated. The characterization of microparticles included the particles morphology and functional group of bioactive compounds. SAS process was carried out at various pressures of 8, 12, and 16 MPa, various extract/PVP ratios of 1:0, 1:10, and 1:20, constant CO2 flow rate of 15 mL/min, and constant solution flow rate of 0.5 mL/min. The result showed that nanoparticles were successfully produced with particle sizes ranging from 175 ± 95 nm to 376 ± 137 nm. Scanning electron microscopy (SEM) images described that irregular shape particles were precipitated from C. xanthorrizha extract solution, and spherical shape particles were formed from C. xanthorrizha/PVP solution. Computational Fluid Dynamic (CFD) simulation has successfully applied to realize the internal flow of the nozzle in micronization of SAS process. The results of this work are expected to improve the applications of the bioactive compounds from natural products in pharmaceutical industry.

Supercritical CO2 assisted extraction of essential oil and naringin from Citrus grandis peel: in vitro antimicrobial activity and docking study.

The extraction of bioactive compounds, including essential oils and flavonoids, using organic solvents is a significant environmental concern. In this work, waste C. grandis peel was the ingredient used to extract essential oil and naringin by conducting a supercritical CO2 technique with a two stage process. In the first stage, the extraction with only supercritical CO2 solvent showed a significant enhancement of the d-limonene component, up to 95.66% compared with the hydro-distillation extraction (87.60%). The extraction of naringin using supercritical CO2 and ethanol as a co-solvent was done in the second stage of the process, followed by evaluating in vitro antimicrobial activity of both the essential oil and naringin. The essential oil indicated significant activity against M. catarrhalis (0.25 mg ml−1), S. pyogenes (1.0 mg ml−1), S. pneumoniae (1.0 mg ml−1). Whilst naringin gave good inhibition towards all tested microbial strains with MIC values in the range of 6.25–25.0 μM. In particular, naringin exhibited high antifungal activity against T. rubrum, T. mentagrophytes, and M. gypseum. The molecular docking study also confirmed that d-limonene inhibited bacterium M. catarrhalis well and that naringin possessed potential ligand interactions that proved the inhibition effective against fungi. Molecular dynamics simulations of naringin demonstrated the best docking model using Gromacs during simulation up to 100 ns to explore the stability of the complex naringin and crystal structure of enzyme 2VF5: PDB.

Towards solvothermal upcycling of mixed plastic wastes: Depolymerization pathways of waste plastics in sub- and supercritical toluene

Solvothermal liquefaction (STL) is a thermochemical conversion process, where a waste feedstock is treated with sub-and supercritical solvents. The key objective of the study was to investigate how a one-step STL using toluene as a solvent can degrade hard-to-recycle waste plastics (#5–#7). Three different plastic wastes namely, polypropylene (#5), polystyrene (#6), and polyurethane (#7), and their equal mixture (by weight, also referred here as mixed plastic wastes) were solvothermally liquefied by toluene in a 7 mL pressure bomb at 300, 350, and 400 °C for 3, 6, and 9 h in order to determine the effect of temperature and time, respectively. The liquid products were separated from the solid residue and further analyzed in terms of the STL conversion, change in elemental compositions via ultimate analysis, boiling point distribution via thermogravimetric analyzer (TGA), alteration of chemical bonds via proton nuclear magnetic resonance spectroscopy (1H NMR), and degradation products via gas chromatography mass spectroscopy (GCMS). The results showed that the STL conversion increase with the increase of reaction temperature and time. From the elemental analysis, it can be predicted that the higher heating values of the crude products are between 30 and 45 MJ/kg. Boiling point distribution showed that the production of lower hydrocarbon (C8–C20) increased significantly from about 10% at 300 °C to 80% at 400 °C. Additionally, product distribution showed that the aromaticity increased with the increase of residence time where the main products are benzene and styrene like products. Overall, it was observed that mixed plastic wastes have a synergistic effect on the degradation products.