Solubility In Supercritical Fluids Research Articles

Fluid revisited: An overlook of a method for solubility measurements in supercritical fluids based on chromatography retention

Measuring solubility in supercritical fluids usually represents a technical challenge since it is a highly compressible media sensitive to sampling and processing. Several decades ago, a chromatographic method for measuring solubility in supercritical fluids was presented by Bartle et al based on a linear relationship between solubility and inverse retention coefficient in supercritical fluid chromatography. Despite clear advantages such as high productivity and simplicity of sample preparation the method received only a limited acceptance in the field. In this work, the method was re-evaluated using several model compounds and stationary phases in supercritical fluid chromatography in conditions close to the limits of method applicability. Effects of calibration approaches, flowrates, initial calibration data and chromatography sample solvents were tested. The method appeared to be surprisingly robust and reasonably precise even for compounds which do not fully comply with the requirements for method applicability. It could be considered as an express method of choice when large sets of solubility data at different pressures are required.

Simulation and Optimization: A New Direction in Supercritical Technology Based Nanomedicine.

In recent years, nanomedicines prepared using supercritical technology have garnered widespread research attention due to their inherent attributes, including structural stability, high bioavailability, and commendable safety profiles. The preparation of these nanomedicines relies upon drug solubility and mixing efficiency within supercritical fluids (SCFs). Solubility is closely intertwined with operational parameters such as temperature and pressure while mixing efficiency is influenced not only by operational conditions but also by the shape and dimensions of the nozzle. Due to the special conditions of supercriticality, these parameters are difficult to measure directly, thus presenting significant challenges for the preparation and optimization of nanomedicines. Mathematical models can, to a certain extent, prognosticate solubility, while simulation models can visualize mixing efficiency during experimental procedures, offering novel avenues for advancing supercritical nanomedicines. Consequently, within the framework of this endeavor, we embark on an extensive review encompassing the application of mathematical models, artificial intelligence (AI) methodologies, and computational fluid dynamics (CFD) techniques within the medical domain of supercritical technology. We undertake the synthesis and discourse of methodologies for calculating drug solubility in SCFs, as well as the influence of operational conditions and experimental apparatus upon the outcomes of nanomedicine preparation using supercritical technology. Through this comprehensive review, we elucidate the implementation procedures and commonly employed models of diverse methodologies, juxtaposing the merits and demerits of these models. Furthermore, we assert the dependability of employing models to compute drug solubility in SCFs and simulate the experimental processes, with the capability to serve as valuable tools for aiding and optimizing experiments, as well as providing guidance in the selection of appropriate operational conditions. This, in turn, fosters innovative avenues for the development of supercritical pharmaceuticals.

Polycyclic aromatic hydrocarbons dissolution in supercritical carbon dioxide by molecular dynamics simulation

With the rapid development of industry, the problem of soil contamination has grown increasingly serious, posing a serious threat to the wellness of people. Polycyclic aromatic hydrocarbons (PAHs) are among the most common soil contaminants. Supercritical CO2 extraction has been widely used to treat PAHs in soils. Solute solubility in supercritical fluids is a fundamental thermophysical parameter that must be investigated and modeled. In this work, we employed molecular dynamics simulation to investigate the microscopic dissolution process in supercritical CO2 of four PAHs: naphthalene, anthracene, pyrene, and benzo(α)pyrene. We also looked into the implications of changing the ring number of PAHs on the ability of supercritical CO2 to dissolve PAHs by calculating the interaction energy, radial distribution function, and the coordination number between PAHs and supercritical CO2. The results indicated that the PAHs’ capacity to dissolve in supercritical CO2 decreased gradually with the increase of ring number. The interaction energy between PAHs and supercritical CO2 decreases as the number of PAHs rings increases. Among them, the van der Waals interaction energy plays a decisive role in the dissolution of PAHs in supercritical CO2. As the number of PAHs rings increased, the positions of the first peak and valley of the radial distribution function remained the same, which appeared at about 4.3 Å and 6.1 Å, respectively. However, the magnitudes of the peaks and valleys decreased. As the number of PAHs rings increased, the coordination number of the C atoms of supercritical CO2 around the C atoms of PAHs decreased.

Supercritical fluid chromatography for the analysis of natural dyes: From carotenoids to flavonoids.

Plant-derived natural dyes are used in a variety of formulated products, from food to cosmetics and pharmaceutics. In addition to their color, they also provide some bioactivity. While they are mostly analyzed with high-performance liquid chromatography, supercritical fluid chromatography was also employed for several dye families, mostly for carotenoids and chlorophylls, and more recently for anthraquinones and flavonoids. These supercritical fluid chromatography methods are described in this review. Because the dyes have different structures and structural variations (polarity, isomers, etc.), the best chromatographic system to achieve their separation is not always the same. Hydrophobic stationary phases are preferred for the most hydrophobic dyes (chlorophylls and carotenoids) while polar stationary phases are preferred for the polar dyes (anthraquinones and flavonoids). Regarding the mobile phase composition, chlorophylls and carotenoids are best eluted with moderate proportions of co-solvent in CO2 (about 40%), while the most polar glycosylated flavonoids require higher proportions of co-solvent and acidic additives. Because dyes are colorful, ultraviolet-visible detection is often sufficient, while mass spectrometry offers additional structural information. Furthermore, fundamental information can also be gained through chromatographic analysis of dyes: either solubility in supercritical fluids, in view of their extraction, or retention behavior providing an understanding of stationary phase properties.

A crossover of the solid substances solubility in supercritical fluids: What is it in fact?

We investigate a well-known phenomenon of the appearance of the crossover points, corresponding to the intersections of the solubility isotherms of the solid compound in supercritical fluid. Opposed to the accepted understanding of the existence of two fixed crossover points, which confine the region of the inverse isobaric temperature dependence of the solubility, we have found that these points tend to shift with the change of the temperature and in the limit of the certain threshold value they converge to a single point. We demonstrate this analyzing the solubility data of a set of poorly soluble drug compounds, which have been computed in a wide area of the phase diagram via the approach, based on the classical density functional theory. Thorough analysis of the available in the literature experimental solubility data is found to be in an agreement with our conclusions, as one can find that the wider temperature region of the experimental study is, the more pronounced effect of the crossover points drift can be observed.

Measuring and modeling the solubility of an antihypertensive drug (losartan potassium, Cozaar) in supercritical carbon dioxide

Developing environmentally friendly processes as supercritical technologies for the pharmaceutical industry producing micro-sized drug particles is crucially important. For achieving such a purpose, the solid drug's solubility in supercritical fluids (SCFs) should be accurately measured and correlated. In this work, the equilibrium solubility of the losartan potassium (L-K), an antihypertensive drug, in supercritical carbon dioxide (SC-CO2) has been determined for the first time. Measurements were carried out at pressures ranging from (120 to 270) bar, and temperatures from (308 to 338) K. Obtained solubilities (presented in mole fraction) are in the range of 2.03 × 10−6 - 1.88 × 10−5and their behavior was examined with respect to the pressure and density of the SC-CO2. The crossover region was observed at about 190 barin all isotherms in term of mole fraction-pressure plots. Some semi-empirical models based on different approaches as activity coefficient and fugacity coefficient were used for correlating solubilities data. The dilute solution -based MST model (Mendez-Santiago-Teja) led to the best AARD with a value of 2.8%, and correlated results with this model endorsed internal consistency of experimental solubility data. Moreover, endothermic process was corroborated with both experimental results and estimated enthalpies.

Silver Solubility in Supercritical Fluids in a Wide Range of NaCl Concentration (0.6–50 wt %)—Experimental and Thermodynamic Description

The solubility of Agcr has been measured in a 0.1m (mol·(kg H2O)−1) solution of HCl at a fixed hydrogen content (∼0.5m) as a function of NaCl concentration from 0.1 to 18m at temperatures ranging f...

STUDY OF SOLUBILITY IN SUPERCRITICAL FLUIDS: THERMODYNAMIC CONCEPTS AND MEASUREMENT METHODS - A REVIEW

Abstract Due to the importance of supercritical fluid technology (SFT) in different industries, it has been the subject of intense research in recent decades. Solubility is a key concept in SFT. In fact, obtaining knowledge about the theoretical concepts of solubility and related experimental measurement methods can be useful in developing and improving the quality of research in this field. This study reviews the fundamental knowledge of solubility in supercritical fluids and investigates the significant topics in this field, including high-pressure phase behavior, experimental measurement methods, modeling, and molecular simulation of solubility.

About consistency of Solid's solubility data in supercritical CO2 and some thermodynamic properties estimation

In chemical industry, usual solvents are being replaced by supercritical fluids. Last few years, extraction by these environmentally benign solvents has had much attention and now is considered as the newest separation technology. However, developing new applications and improving existing ones is based on a set of thermodynamic and physical properties of pure solutes related to phase equilibrium for which experimental values cannot be found and consequently, there is an increase need for accurate estimates of these properties. This paper is interested firstly to a thermodynamic property which is the Krichevskii parameter and secondly to a thermophysical one which is the sublimation pressure. First parameter is considered as a governor of thermodynamic properties in binary dilute mixtures near the solvent's critical point and can be calculated from some rigorous relationships and in this paper a review and a new way for its estimation are presented based on consistency of solid's solubility data in supercritical fluids and dilute solution theory. Second parameter is considered as the predominant influencer on solubility in supercritical fluids and unavailability of its experimental values presents an obstacle to thermodynamic modeling of solubility data. For this reason and as a second step, in this paper we present a new manner for its estimation. Obtained results are relevant, very promising for each considered property and the methodology can be applied for other solutes with more complex structures as Pharmaceuticals (antibiotics, drugs, anti-inflammatories …), polycyclic aromatic hydrocarbons (PAHC) and dyestuffs.

Solubility modeling of supercritical fluid extraction in a wide range compounds: comparison between fuzzy-genetic and new empirical models

ABSTRACTIn the current study, two methods based on a new empirical equation and fuzzy-genetic model are proposed to estimate solute solubility in supercritical fluid (SCF). New proposed models are trained with comprehensive dataset collected from literature with more than 3,260 experimental data at different temperature and pressure. In order to testify the accuracy, the proposed models are compared to other empirical equations. The amounts of average values of absolute relative deviation ()were obtained 7.74% for fuzzy-genetic model and 9.27% for new proposed empirical model. The reasonable accuracy of developed models for estimating the solubility of solutes in SCF extraction process is represented. From literature solubility data, the authors obtained new estimation models for solute solubility in CO2 supercritical which are in agreement with measured experimental values.

Estimation of critical point, vapor pressure and heat of sublimation of pharmaceuticals and their solubility in supercritical carbon dioxide

The critical point and vapor pressure of pharmaceuticals are required in the calculation of their solubility in supercritical fluids by using an equation of state. The experimental critical point of many pharmaceuticals are not accessible due to their temperature sensitivity, also the experimental vapor pressure of many pharmaceuticals are not available at temperatures at which the supercritical extraction is usually accomplished. In this study, four group contribution methods are used to estimate the critical point and acentric factor of eight pharmaceuticals. The estimated properties are evaluated in predicting the vapor pressure and enthalpy of sublimation of the pharmaceuticals by using the Peng Robinson equation of state. The most accurate critical points are employed to calculate the solubility of the pharmaceuticals in the supercritical CO2 by using the Peng Robinson equation combined with two mixing rules. The AARD of 7.28% indicates the good performance of the Wong Sander mixing rule.

Peng–Robinson Equation of State Model for Polycyclic Aromatic Hydrocarbons and Long-Chain Hydrocarbons Solubilities in Supercritical Fluids. Correlations Based on Solute Molecular Properties

The Peng–Robinson equation of state (EOS) with the classical van der Waals quadratic mixing rules is used in this study to calculate the solid solubilities of polycyclic aromatic and long chained hydrocarbons in supercritical carbon dioxide, ethane, and ethylene. The effect of the binary interaction parameters kij (for parameter a) and lij (for parameter b) in the van der Waals mixing rules, on the pressure dependence of the solute solubility in the supercritical fluid is examined. The addition of a third parameter, λ2, that modifies the pure component covolume parameter b of the solute, significantly enhanced the ability of the EOS to fit the experimental data. Reasonable optimally fitted binary interaction parameters kij and lij and pure component parameter λ2 were obtained. The EOS parameters were correlated with molecular properties and can be used as estimates for predicting solubilities when experimental data is missing. A phase stability test is proposed to guarantee that the stable root is always ...

Solubility of the silver nitrate in supercritical carbon dioxide with ethanol and ethylene glycol as double cosolvents: Experimental determination and correlation

Abstract Solubility of the silver nitrate in the supercritical carbon dioxide containing ethanol and ethylene glycol as double cosolvents was measured under certain pressure and temperature range (10–25 MPa, 323.15–333.15 K). The impact of the pressure and temperature on the solubility was also investigated. Based on the experiment data, a correlation model concerning solid's solubility in supercritical fluids was established by combining the solubility parameter with the thermodynamic equation when a binary interaction parameter and a mixed solvent solubility parameter were defined. Experiments show the solubility of AgNO3 increases with the pressure at a certain temperature. However, the influence of temperature is related to a pressure defined as the turnover pressure (12.3 MPa). When the pressure is higher (or lower) than this turnover pressure, silver nitrate's solubility shows increasing (or decreasing) trend as the temperature rises. Satisfactory accuracy of our presented model was revealed by comparing experimental data with calculated results.

A new chemical structure-based model to estimate solid compound solubility in supercritical CO2

Utilization of new approaches in the determination of drug solubility in supercritical fluids can reduce the computation time and represent reliable results. This also leads to more applications of the supercritical technology in the field of drug manufacturing. A least-square support vector machine (LSSVM) approach is employed in this study in order to predict 33 different drug solubility in supercritical CO2. The solubility of the drugs is estimated as a function of temperature, pressure, supercritical CO2 density, and 20 different chemical substructures. LSSVM results are then compared to those obtained from 8 previously reported semi-empirical correlations. Satisfying predictions are performed by the proposed LSSVM with an average absolute relative deviation of 4.92% and determination coefficient of 0.998 for the testing dataset. Therefore, the proposed LSSVM can be applied as a reliable predictive tool to estimate the drugs’ solubility, if drugs’ chemical structures are given.

Efficient modeling of drug solubility in supercritical carbon dioxide

Development of new models and correlations to determine the drug solubility in supercritical fluids, i.e., supercritical CO2, helps us to avoid time-consuming computations with poor outcomes while improving the supercritical technology. In this communication, a supervised technique, namely, the least square support vector machine (LSSVM) was employed to estimate the solubility of 33 different drug compounds in supercritical CO2. The corresponding solubility was determined as a function of temperature, pressure, density of supercritical CO2, and two physical properties of drug, i.e. molecular weight and melting point. The results obtained from the employed LSSVM model were compared with eight correlations. The obtained average absolute relative deviation and the square of regression coefficient for the testing group of LSSVM model were found to be 5.61% and 0.9975, respectively. Therefore, the model developed in this work can be reliably applied to the studied drugs by only knowing their physical properties.

A new empirical model to correlate solute solubility in supercritical carbon dioxide in presence of co-solvent

In this work, correlation of solute solubility in supercritical fluid in presence of co-solvent has been carried out using a new density-dependent empirical equation. The new model has five parameters for each system. The parameters of the new correlation have been obtained for various ternary systems including 1668 experimental solubility data. The overall percent of absolute average deviations (%AARD) are 1.57 and 2.35 using different density calculation methods The comparisons of the new equation and the published models show its good capability in calculating solute solubility in supercritical fluid in presence of co-solvent.

Measurement and Correlation of Curcumin Solubility in Supercritical Carbon Dioxide

Curcumin is a natural phenolic pigment extracted from turmeric and has a good pharmacological activity in anti-inflammatory, antioxidant, hypolipidemic, and antitumor. It has been frequently used in drug-loaded microspheres recently. However, the reports on its solubility in supercritical fluids have not been seen yet. In the present study, solubility of curcumin in the supercritical carbon dioxide (ScCO2) was determined using the dynamic equilibrium method. The experimental measurements were performed at temperatures of 35, 45, and 55 °C and pressure range from 8 to 20 MPa. The measured data showed that the solubilities of curcumin were between 1.82 × 10–8 and 1.97 × 10–6 (mole fractin) for the corresponding temperatures and pressures. The effects of temperature, pressure, and with and without ethanol cosolvent on the solubility were investigated. The measured solubilities were calculated and correlated by semi-empirical formulas Chrastil and Mendez-Santiago and Teja models. The results showed that the e...

A predictive approach for thermodynamic modeling of solubility in supercritical fluids using genetic algorithm

The interaction parameter kij used in various mixing rules is not always available. The present work deals with its determination using a group contribution approach which itself is based on group interaction parameters. To date the interaction parameters matrix concerns twelve groups only. Therefore new parameters were determined by optimizing a well defined objective function by means of the genetic algorithm (GAs) and using the Predictive Soave Equation of State (PSEOS) with the van der Waals mixing rule (VDW MR), considering the solubility of organic solutes in supercritical carbon dioxide at elevated pressure ranging from 60 to 350 bar.

Modified Wilson's Model for Correlating Solubilities in Supercritical Fluids of Some Polycyclic Aromatic Solutes

ABSTRACTSince developing mathematical models is extremely useful to determine solubilities of various solutes in supercritical fluids (SCFs); in this work, the “expanded liquid” approach is adopted to predict the solubility of some polycyclic aromatic solutes (with different size, functionality, and polarity) in diverse SCFs. A modified form of the Wilson's model is proposed for predicting the solubilities of the considered binary systems by computation of the activity coefficient based on the local composition concept. Effect of high operating conditions is considered via the variation of the molar volume of the solute. The proposed correlation achieves an overall and average AARD of 9.2% and 7.8%, respectively, on a range of 1.14% to 19.9%, these results show that the predicted solubility data are in good agreement with the experimental ones. Moreover, dependence of binary parameters on density and some solute's characteristics is discussed on the base of their course versus solvent reduced density.

Determining the Solubility of Organic Compounds in Supercritical Carbon Dioxide Using Supercritical Fluid Chromatography Directly Interfaced to Supercritical Fluid Solubility Apparatus

The solubilities of benzoin and 3,3′,4,4′-benzophenonetetracarboxylic dianhydride in supercritical fluid carbon dioxide have been measured using static supercritical fluid solubility apparatus directly interfaced to supercritical fluid chromatography (SFC). The method involves increasing the pressure of supercritical fluid carbon dioxide in controlled steps to produce a series of saturated sample solutions that are sequentially analyzed by online SFC. The system requires minimal manual sample manipulation stages and facilitates a self-validation check procedure. Solubility data for benzoin was determined at 308 and 318 K through the pressure range of 12–24 MPa using 2 MPa steps. Solubility data for 3,3′,4,4′-benzophenonetetracarboxylic dianhydride was determined at 328 and 343 K through the pressure range 15–27.5 MPa using 2.5 MPa steps. The Mendez-Santiago and Teja model has been successfully applied to correlate all sets of experimental solubility data.