Solubility In scCO2 Research Articles

Influence of solvent selection and RESS processing conditions on formation of a praziquantel-malonic acid cocrystal in supercritical CO2

Praziquantel (PZQ) is an anthelmintic drug with low solubility, therefore cocrystallization and particle size reduction is desirable to improve bioavailability. In this study, a PZQ-malonic acid cocrystal was micronized by rapid expansion of supercritical solution (RESS). Due to low solubility in scCO2, four cosolvents were screened as RESS modifiers. While addition of acetone or THF yielded mixtures of PZQ and its cocrystal, MeOH and EtOH produced pure cocrystal. Impact of pressure (15–30 MPa), temperature (35–55 °C), and cosolvent loading (3–10 volumes) on phase-purity, yield, and particle size were investigated. Adding cosolvent to RESS facilitated dissolution of cocrystal formers in scCO2 and crystallization of the cocrystal with yields up to 68.5 wt% and particle size as low as 600 nm. Results show that for APIs with low solubility in scCO2, cosolvent-modified RESS is a suitable approach for simultaneous crystallization and micronization.

Solubility of supercritical CO2 in polystyrene

Expanded polystyrene (ePS) plays an important role in the food packaging industry. However, the foaming process is environmentally unfriendly. A sustainable alternative is dissolving supercritical CO2 (scCO2) in the polystyrene (PS) matrix. Most studies so far were performed at temperatures above the PS glass transition temperature; however, a more general temperature window is desirable. In this work, the solubility of scCO2 in polystyrene was measured at 323 K, 343 K, 363 K and 383 K and pressure up to 130 bar using a magnetic suspension balance (MSB). It was concluded that the solubility of CO2 in PS decreases with temperature and increases with pressure. The Sanchez-Lacombe Equation of State was utilized to estimate the degree of swelling. The model developed was able to derive the experimentally determined solubilities after correction for the swelling. The interaction parameter, k12, turned out to be only a function of temperature. With these results the solubility and swelling of PS in scCO2 can be more accurately assessed for different temperatures and pressures.

The self-assembly of water reverse micelles with imidazolium ionic liquids in supercritical carbon dioxide: A molecular dynamics simulation study

Molecular dynamics (MD) simulations were employed to investigate the self-assembly of water reverse micelles (RMs) with imidazolium ionic liquids (ILs) stabilized by dodecyl polyoxyethylene (3) polyoxypropylene (6) ether (LS-36) in supercritical carbon dioxide (scCO2) at 308 K and 20 MPa. The study explored the impact of various factors, including the IL concentration, the alkyl chain length of the imidazolium cations (1-ethyl-3-methylimidazolium [EMIM]+, 1-octyl-3-methylimidazolium [OMIM]+), and the anion type (bis(trifluoromethylsulfonyl)imide [NTf2]-, tetrafluoroborate [BF4]-, acetate [ACE]-) on the solubilization of ILs by water reverse micelles. The findings revealed that water, ILs, and the surfactant formed spherical RMs in the fluid phase, with varying structures depending on the hydrophobicity of the IL. The presence of ILs was found to expedite the self-assembly process and increase the number of assembled surfactants. Higher IL concentrations resulted in greater water content in the polar core of the RMs and reduced water solubility in scCO2. The intermolecular interactions occurring between components of the systems as well as dynamical properties are discussed in terms of radial distribution functions, density distribution, hydrogen bond number and lifetime, number of contacts, and self-diffusion coefficients.

Microencapsulation of pyriproxyfen using the particles from gas‐saturated solutions process as a controlled‐release system

AbstractThe purpose of this investigation was to determine whether pyriproxyfen (PPF), a synthetic juvenile hormone analog (JHA), could be encapsulated in supercritical carbon dioxide (scCO2) using the process particles from the gas‐saturated solutions (PGSS) for a controlled‐release system. The PGSS process represents a promising two‐step production system especially suited for the encapsulation and controlled‐release system (CRS). In contrast to traditional encapsulation methods that often involve the use of harsh organic solvents or high temperatures, the PGSS process offers a gentler approach employing scCO2 as an alternative. The solubility of scCO2 in polymer (poly‐ϵ‐caprolactone [PCL]) allowed for the formation of PPF microparticles, and the particle size distribution could be controlled by adjustment of operating pressure and temperature. The obtained particles had a mean particle size of 73.6 ± 2 μm and encapsulation efficiency of 78.8 ± 9% at 60°C and 10 MPa. Furthermore, the in vitro dissolution profiles of PPF–PCL particles showed a low‐level release pattern (42.5 ± 5 ppb/d) in water, followed by zero‐order kinetics indicating a high‐performance CRS. Finally, the in vivo bioassay using microparticles treated water exhibited 95%–100% emergence inhibition of mosquitoes, suggesting the effectiveness of PPF–PCL particles as a mosquito control agent.

Experimental and thermodynamic investigation of gemifloxacin solubility in supercritical CO2 for the production of nanoparticles

The effective use of the supercritical technology in the production of new pharmaceutical formulations with greater bioavailability requires the determination of the solubility of pharmaceutical substances in supercritical CO2 (scCO2) at different conditions. In the current work, the solubility of an antibacterial compound, Gemifloxacin, was measured at various temperatures (308 to 338 K), and pressures (120 to 300 bar). This compound has a poor solubility in scCO2 (0.02 × 10−4 to 0.67 × 10−4 mole fraction or 0.0156 to 0.5891 g.kg−1). Furthermore, some popular empirical models and three thermodynamic approaches (SRK and PR equations of state, and the regular solution model) were applied to correlate and predict the solubility of Gemifloxacin in scCO2. The regular solution model with temperature-dependent solubility parameter (mean AARD% = 2.32–4.34) and the SRK-based model (mean AARD% = 7.47), exhibited the highest accuracy in fitting the experimental data.

A method to improve dye-uptakes of less soluble disperse dyes for polyester fibers in supercritical CO2 fluid: A theoretical and experimental study

Two organic small molecules were used as assist-dissolving agents to increase the solubility of some dyes in ScCO2. Theoretical calculations showed that nicotinamide was better than benzoic acid. AIM and IGMH methods confirmed the hydrogen bonding and π-π stacking interactions between the agents and dyes. The mixtures of agents and dyes were made by the physical grinding and mixing method, and their solubilities and melting points were tested. The results indicated that the agents reduced the intermolecular forces in the dye crystals, thus enhancing the dye solubility in ScCO2. The dyeing experiment also proved the improvement of dyeing performance by the agents. The dye uptake increased from 20%∼30% to 60%∼70%, and the color intensity of the fibers improved. The best operating parameters were a temperature of 130 ℃ and a pressure of 28 MPa. The hue and color fastness of the dyed products were similar to those dyed with pure dyes.

Solubility measurement of Triamcinolone acetonide (steroid medication) in supercritical CO2: Experimental and thermodynamic modeling

Triamcinolone Acetonide (TA, Steroid Medication) solubility in supercritical carbon dioxide (ScCO2) was determined for the first time at 308, 318, 328, and 338 K and pressures of 120–270 bar. The results showed that mole fractions of TA dissolved in ScCO2 ranged from 6.90 × 10−6 to 2.13 × 10−4, and the solubility ranged from 0.052 to 1.650 g/L. Four different types of models were examined; (1) seven known density-based models, with 3–6 adjustable parameters, namely Sung-Shim, Chrastil, Kumar–J and Bian et al., MST, Bartle, and Sodeifian; (2) Equation of state (EoS) based model, specifically Peng-Robinson (PR) EoS, coupled with two conventional types of van der Waals mixing rules; (3) a Solid-Liquid Equilibrium (SLE) based model, developed by Soedifian et al.,; (4) several machine learning-based models, namely Ridge Regression, Huber Regression, Random Forest, and Gaussian Process. Based on the results, all applied models accurately described TA solubility in ScCO2, although Sodeifian et al. model led to superior results based on AARD% and Kumar–Johnston model based on Bayesian Information Criterion (BIC). Finally, thermodynamic enthalpies of TA were estimated for the first time.

Analysis of nanomedicine production via green processing: Modeling and simulation of pharmaceutical solubility using artificial intelligence

This research focuses on investigating the solubility of tolfenamic acid in SC-CO2 (supercritical carbon dioxide) and the density of SC-CO2 solvent via theoretical artificial intelligence method. The study involves analyzing the relationship between temperature, pressure, and the corresponding mentioned outputs for the process. Three different predictive models, namely Multi-layer Perceptron (MLP), Polynomial Regression (PR), and Extra Trees (ET) are utilized to forecast the solubility of drug and the density of solvent (SC–CO2). The models are fine-tuned with hyper-parameters using the Dragonfly Algorithm (DA) to ensure accurate predictions. The solubility prediction is remarkably accurate using the MLP model, showing a high score of 0.98329 in terms of R-squared. The maximum error is 0.2474, and the MAE is 0.1095, demonstrating the model's high precision in estimating tolfenamic acid's solubility in SC-CO2. The PR model demonstrates exceptional accuracy, yielding a score of 0.99844 by R-squared metric, a maximum error of 0.068, and an MAE of 0.0314. The ET model also performs well, with an R-squared score of 0.90977, a maximum error of 0.445, and an MAE of 0.1665. Regarding density prediction, MLP outperforms the other techniques, achieving a significant R2 parameter of 0.99919, an MSE of 12.663, and a mean MAPE of 0.0037.

Solubility of famotidine in supercritical carbon dioxide: Experimental measurement and thermodynamic modeling

In the current study, the solubility of famotidine (FAM) in supercritical carbon dioxide (scCO₂) was experimentally determined for the first time. The FAM solubility in scCO₂, expressed as mole fraction, at different temperatures (308 − 338 K) and pressures (12 − 30 MPa) was found to be in the range of 1.40 × 10−6 to 1.11 × 10−4. Due to the low solubility of FAM in scCO₂, the gas anti-solvent and supercritical anti-solvent processes can be a good option to generate the nano/micro size particles of this drug. The experimental solubility data were correlated by the density-based models of Bartle et al., Méndez-Santiago and Teja (MST), Jouyban et al. and Hozhabr et al., by the non-cubic equation of state PC-SAFT, and by the two versions of the Estévez et al. model (ECM-PR and ECM-RK). According to the modeling results, the Estévez et al. model showed the highest accuracy with AARD values of 9.92 (ECM-PR) and 10.70 (ECM-RK). The empirical models also yielded satisfactory outcomes to the correlation of the solubility of FAM in scCO₂.

Supercritical carbon dioxide-assisted gold metallization of 3D-printed structure and the tensile strength

Gold metallization of 3D printed polymer structures was conducted by a supercritical carbon dioxide (sc-CO2) assisted electroless plating process. Precursor of the Pd catalyst utilized in this study was palladium bis-hexafluoroacetylacetonate for the high solubility in sc-CO2. A Ni–P layer was first formed on the catalyzed polymer structure as a sacrificial layer for the sequential gold deposition. Electrical resistance of the gold metallized 3D printed structure was 0.15 Ω and slightly increased to 0.18 Ω after a tape adhesion test. The fracture strength was 47.6 MPa for the sample with 45 min of the gold deposition time.Graphical abstract

Solubility of tris(2-methylbutyl) phosphate in supercritical carbon dioxide and its application for the recovery of uranium from U-Zr and U-Th aqueous solutions

The employment of supercritical fluid extraction (SFE) within the nuclear industry may reduce the environmental burden by reduction in solvent waste generation. In this perspective, a SFE based method was developed for selective extraction of uranium from U-Zr and U-Th solutions using tris-(2-methylbutyl) phosphate (T2MBP) as a ligand in supercritical carbon dioxide (SCCO2). Prior to SFE studies, the utilisation of T2MBP in SCCO2 was examined by carrying out solubility measurements using dynamic flow technique at (313−333) K and (10−20) MPa. T2MBP has sufficient solubility in SCCO2 and ranges from 2.55 × 10-2 mol·mol-1 to 8.95 × 10-2 mol·mol-1. The solubility increases with pressure and decreases with temperature, resulting in retrograde solubility behaviour. The experimental solubility data was successfully correlated using different density based semi-empirical equations. Based on the solubility data, selective recovery of uranium from U-Zr and U-Th solutions was demonstrated using SCCO2+T2MBP.

Study of Hyoscine solubility in scCO2: Experimental measurement and thermodynamic modeling

In this research, solubility of Hyoscine, as the most well-known drugs used to relieve spasmodic abdominal pain, in supercritical carbon dioxide (scCO2) was determined at 170–410 bar for pressure and 308–348 K for temperature. It was found 0.79 × 10-4 to 2.83 × 10-4 of equilibrium mole fraction and 0.3 × 10-2 to 1.65 × 10-2 kg.m−3 of equilibrium solubility. Also, obtained experimental data was correlated by common empirical models; Bartle, Chrastil, Mendez-Santiago, Kumar, and Johnston (K-J), and Teja (MST). All these models could satisfactorily correlate the experimental data with high accuracy. Among them, the MST model with the lowest AARD% value (2.942) and the highest Radj value (0.991) possesses the highest correlation precision. Furthermore, the total heat of mixing, enthalpy of vaporization, and enthalpy of solvation for the Hyoscine-scCO2 system were computed, as 20.76 kJ.mol−1, 35.71 kJ.mol−1, and −14.95 kJ.mol−1, respectively.

Solubility of palbociclib in supercritical carbon dioxide from experimental measurement and Peng–Robinson equation of state

Palbociclib is a poorly water-soluble medicine which acts against metastatic breast cancer cells. Among various techniques to improve the solubility of this medicine, applying supercritical technologies to produce micro- and nano-sized particles is a possible option. For this purpose, extraction of solubility data is required. In this research, the solubility of palbociclib in supercritical carbon dioxide (ScCO2) at different equilibrium conditions was measured at temperatures between 308 and 338 K and pressures within 12–27 MPa, for the first time. The minimum and maximum solubility data were found to be 8.1 × 10–7 (at 338 K and 12 MPa) and 2.03 × 10–5 (at 338 K and 27 MPa), respectively. Thereafter, two sets of models, including ten semi-empirical equations and three Peng–Robinson (PR) based integrated models were used to correlate the experimental solubility data. Bian’s model and PR equation of state using van der Waals mixing rules (PR + vdW) showed better accuracy among the examined semi-empirical and integrated models, respectively. Furthermore, the self-consistency of the obtained data was confirmed using two distinct semi-empirical models. At last, the total and vaporization enthalpies of palbociclib solubility in ScCO2 were calculated from correlation results of semi-empirical equations and estimated to be 40.41 and 52.67 kJ/mol, respectively.

Coloration Modeling and Processing of Commodity Plastic Buttons in Supercritical Carbon Dioxide.

We examined the color processing of the commodity plastic buttons made of acrylic, polyester, nylon, and casein with scCO2. The buttons' dyeing color depth (K/S) was measured over a wide range of scCO2 and correlated accurately with the response surface method. Moreover, we measured the solubility of C.I. Disperse Red 22 in scCO2 to formulate a dye-sorption model for the K/S value in the color processing of the plastic buttons. Finally, the dye-sorption model for the K/S value combining the dye solubility in scCO2 with the dye diffusion inside the buttons successfully represented the color processing of the buttons.

Dynamics simulation of the effect of cosolvent on the solubility and tackifying behavior of PDMS tackifier in supercritical CO2 fracturing fluid

Due to the low viscosity of supercritical carbon dioxide (SC-CO2) fracturing fluid, the method of adding tackifier is generally chosen to improve its sand carrying ability. Recently, siloxane-based tackifier has been widely utilized because of low cohesive energy and good viscosity building properties, but cosolvents are somehow needed to be added in the system to improve its solubility in SC-CO2. In this study, polydimethylsiloxane (PDMS)- a widely used siloxane polymer- was selected as the object tackifier. First, the effects of the addition of cosolvents such as ethanol, acetic acid, cyclohexane and toluene on dissolution behaviors of PDMS in SC-CO2 fracturing fluid were investigated by molecular dynamics simulation. Moreover, the solubilization effects of polar and nonpolar cosolvents on PDMS in SC-CO2 fracturing fluid were studied by comparing the binding energy, cohesive energy density and radial distribution function between solvent-solvent and between solvent-solute. The simulation results showed that cyclohexane could improve the solubility parameters of SC-CO2 the most at the same cosolvent concentration, and SC-CO2 was more uniformly distributed in the system. Meanwhile, the interactions between toluene and SC-CO2 was the strongest, and SC-CO2 was generally uniformly distributed in the system. However, ethanol and acetic acid performed poorly because they could produce hydrogen bonds with certain directionality and saturation. It was revealed that the mechanism of using cosolvents to improve the solubility of PDMS in SC-CO2 was based on the equilibrium of intermolecular forces between CO2 and PDMS, between CO2 and cosolvent, and between PDMS and cosolvent. When the siloxane-based tackifier was a nonpolar material, cyclohexane was recommended as the cosolvent. If the siloxane-based tackifier itself had some weak polarity, toluene was more suitable.

Experimental - Theoretical approach for determination of Metformin solubility in supercritical carbon dioxide: Thermodynamic modeling

Metformin, as an anti-hyperglycemic, is the main medicine for treating diabetes of type II. However, its daily dose is high due to its incomplete absorption and short half-life, which leads to digestive problems and patient complaints. Controlled release and increased bioavailability of this drug can be achieved using novel drug delivery systems produced with an appropriate supercritical carbon dioxide (scCO2) method. However, the solubility of Metformin in scCO2 is an essential parameter for this purpose which needs to be evaluated prior to the processing. In the current research, solubility of Metformin in scCO2 was determined at temperatures of 308, 318, 328, and 338 K, and pressures of 140, 170, 200, 230, 260, and 290 bar. It was obtained between 0.39 × 10−6 up to 1.23 × 10−6 (mole fraction). Also, the resulting values were correlated through an equation of state (Peng-Robinson (PR-EoS)) and eight well-known empirical correlations (Chrastil, Sung and Shim, Adachi and Lu, Si-Moussa, Bartle, Jafari Nejad, Keshmiri, and Jouyban). The average AARD% value of 8.24 for the PR-EoS model confirmed its satisfactory precision to predict the Metformin solubility in scCO2. Among the mentioned empirical models, the models defined by Jafari Nejad (AARD% of 4.36 and AICc of −997.07) and Keshmiri (AARD% of 4.73 and AICc of −1048.81) show the highest correlation accuracy. Moreover, the total mixing heat, the vaporization enthalpy, and the solvation enthalpies of the Metformin-scCO2 mixture were computed.

Supercritical carbon dioxide solubility measurement and modelling for effective size reduction of nifedipine particles for transdermal application

Nifedipine (NIF) is a Class II drug of the Biopharmaceutical Classification System (BCS) with low oral bioavailability, low dissolution rate and significant hepatic drug metabolism. The transdermal route using supersaturated systems could be considered. For this purpose, physicochemical properties of NIF such as its dissolution rate, may be a limiting factor and must be improved. Crystallization processes assisted by supercritical carbon dioxide (scCO2) and particularly the Rapid Expansion of Supercritical Solution (RESS) process may improve drug bioavailability by reducing particle size and consequently increasing surface area. This study addresses the reduction of NIF particle size using scCO2-RESS as crystallization process. Experimental solubility studies were performed at different temperature (308 and 318 K) and pressure ranges (9–24 MPa). Solubility data were correlated with two thermodynamic models in order to predict NIF solubility in scCO2. Optimized operating conditions, identified by thermodynamic modelling, allowed the production of thinner NIF particles and a size reduction up to ten fold. Particle size reduction improved NIF dissolution kinetics in aqueous medium: after 90 min, 42 % of raw NIF was released against 80 % for crystallized NIF. The scCO2-RESS process is a solvent free process, that can produce micronized or nanosized crystals able to improve physicochemical properties of poorly water-soluble drugs.

Theoretical and experimental study on Chloroquine drug solubility in supercritical carbon dioxide via the thermodynamic, multi-layer perceptron neural network (MLPNN), and molecular modeling

The design and development of supercritical carbon dioxide (sc-CO2) based processes for production of pharmaceutical micro/nanoparticles is one of the interesting research topics of pharmaceutical industries owing to its attractive advantages. The solubility of drugs in sc-CO2 at different temperatures and pressures is an essential parameter which should be determined for this purpose. Chloroquine as a traditional antirheumatic and antimalarial agent is approved as an effective drug for the treatment of Covid-19. Pishnamazi et al. (2021) measured the solubility of this drug in sc-CO2 at the pressure range of 120–400 bar and temperature range of 308–338 K, and correlated the obtained data using some empirical models. In this work, a comprehensive computational approach was developed to more accurately study the supercritical solubility of Chloroquine. The thermodynamic models include two equations-of-state based models (Peng-Robinson and Soave-Redlich-Kowang) and two activity coefficient-based models (modified Wilson's and UNIQUAC)), as well as, a multi-layer perceptron neural network (MLPNN)) were used for this purpose. Also, molecular modeling was performed to study the electronic structure of Chloroquine and identify the potential centers of intermolecular interactions during the dissolution process. According to the obtained results, all of the theoretical models can predict Chloroquine solubility in sc-CO2 with acceptable accuracy. Among these models, the MLPNN model possesses the highest precision with the lowest average absolute relative deviation (AARD%) of 1.76 % and the highest Radj value of 0.999.

Exploring the relationship between food-grade wax solubility in supercritical carbon dioxide and resulting hydrophobic development of impregnated paper substrates

Alkyl ketene dimer (AKD) and vegetable wax (VW) are suitable contenders for supercritical impregnation (SCI) processes, where the waxes may be deposited onto paper fiber surfaces to improve their hydrophobicity for food packaging applications. The solubility of both waxes in supercritical carbon dioxide (scCO2) with n-heptane cosolvent was measured (40 – 60 oC and 10 – 18 MPa). VW was two orders of magnitude more soluble in scCO2 compared with AKD, and both sets of data were validated using the Chrastil empirical equation. SCI of AKD wax into paper matrixes was performed at pre-determined solubility conditions, and the resulting hydrophobicity was measured. Results demonstrated that annealing the samples (4 h, 140, 160, 180 oC) immediately following impregnation generally enabled a more rapid development of the CA over a 2-week period. Crucially, using impregnation temperatures and pressures that maximized AKD solubility in scCO2 resulted in CA up to 130o. Gravimetric analysis of the impregnated samples confirmed the expected deposited wax quantities to within 25% of the solubility quantities. Scanning electron microscopy (SEM) imaging revealed better distribution of AKD in annealed samples and partially confirmed that more intricate structures were responsible for higher measured CA. These results explicitly connect the intuitive relationship that higher solute solubility in scCO2 should lead to bulk property improvements (i.e. higher CA or hydrophobicity) after SCI. Continued research in this area will enable the development of metrics, linking solubility conditions to desired bulk material properties, and is expected to lead to innovative packaging of green materials and processes.

Experimental evaluation and thermodynamic analysis of Febuxostat solubility in supercritical solvent

In order to develop novel supercritical carbon dioxide (scCO2)-based processes in the pharmaceutical industry, it is necessary to determine the solubility of drugs in scCO2.In the current study, the solubility of Febuxostat(FBX), as a reducer the blood uric acid levels in patientswith gout, in sc-CO2 was experimentally determined at various temperatures of 308 to 338 K and pressures of 120 to 270 bar. The minimum of the FBX solubility in scCO2 (0.05 × 10-4 of mole fraction) and its maximum value (7.42 × 10−4 of mole fraction) gained at the maximum temperature (338 K) and different pressures of 100 bar and 270 bar. Furthermore, obtained data were correlated by some theoretical empirical models; Chrastil and Bartle models with 3 adjustable parameters, Sung and Shim and Hozhabr models with 5 adjustable parameters, and Adachi and Lu and Keshmiri models with 6 adjustable parameters. The models proposed by Keshmiri (AARD% of 10.630 and Radj of 0.987), and Adachi and Lu (AARD% of 13.304 and Radj of 0.985) showed the highest accuracy to correlate the experimental data. Also, the total mixing heat (ΔHtotal), vaporization entalphy (ΔHvap), and solvation enthalpy (ΔHsol) of the FBX-scCO2 system were approximately obtained as 37.26 kJ mol−1, 64.79 kJ mol−1, and −27.53 kJ mol−1.