Experimental Solubility Research Articles

The effect of water on the crystallization of phytosterols and phytostanols in organic solutions

Phytosterols (C29H50O), also known as plant sterols and stanols, are valuable biomolecules with a variety of applications in the pharma, food, and cosmetics industries. Phytosterols are typically manufactured from vegetable oil and tall oil feedstocks through a cooling crystallization process. Depending on the feedstock used, the composition regarding individual phytosterols and phytostanols (saturated analogs of phytosterols), also varies to a large extent. In the current research it was observed that by adding a small amount of water to the organic solvent [i.e., n(water)/n(acetone) of 0.17, n(water)/n(ethanol) of 0.13, and n(water)/n(ethyl acetate) of 0.10], the final phytosterol profile regarding phytosterol and phytostanol concentrations can be modified. This can be explained by the different solubility behavior of phytosterols and phytostanols in the studied solvent systems, based on experimental results obtained from transmissivity measurements. Phytostanols have surprisingly low solubility when compared to phytosterols in all the studied solvent systems. However, in the presence of water, phytosterol solubility decreased more compared to phytostanols. To the best of our knowledge, this is the first time that phytostanol solubility has been systematically studied. Moreover, phytosterol and phytostanol concentrations in a crystallized product with varying binary solvent systems containing water has not previously been reported. The measured experimental solubility data correlated well with the studied solubility models (van't Hoff, modified Apelblat, Buchowski-Ksiazaczak (λh), and polynomial equations). Understanding the solubility behavior of phytosterols and phytostanols allows to optimize the crystallization process itself toward a broader raw material selection, and better yield and quality in the production of phytosterols from plant-based raw materials. In addition, these findings can potentially be further utilized in phytosterol formulations for various applications.

Solubility measurement, correlation, and thermodynamic analysis of ε-CL-20 in four binary solvents (ethyl acetate + halogenated hydrocarbon) from 288.15 to 328.15 K

In this work, the solubility of ε-CL-20 in four binary solvents composed of ethyl acetate and halogenated hydrocarbons (bromobenzene, chlorobenzene, dibromomethane, 1,1,2,2-tetrachloroethane) was measured over the temperature range of 288.15–328.15 K at 0.101 MPa by gravimetric method. Under similar conditions, the order of solubility of ε-CL-20 is ethyl acetate + bromobenzene ≈ ethyl acetate + chlorobenzene > ethyl acetate + dibromomethane > ethyl acetate + 1,1,2,2-tetrachloroethane and the solubility decreases with the increase of halogenated hydrocarbon content. The results also reveal that the solubility is negatively correlated with temperature when the mole fraction of halogenated hydrocarbons is low, otherwise the result is opposite. The modified Apelblat model, van’t Hoff model, CNIBS/R-K model, Jouyban-Acree model and Jouyban-Acree-van’t Hoff model were used to correlate the experimental solubility data and all of the models perform well. The modified Apelblat model and Jouyban-Acree-van’t Hoff model are relatively excellent. The dissolution thermodynamic properties of ε-CL-20 in four binary solvents were calculated and analyzed. The results show that the dissolution processes of ε-CL-20 are entropy-driven non-spontaneous processes. This work is significant to the design and optimization of the crystallization of ε-CL-20.

Development and Validation of HSPiP- and Optimization-Assisted Method to Analyze Tolterodine Tartrate in Pharmacokinetic Study

A new approach was applied for the development of a precise, simple, and economic analytical process for the accurate analysis of tolterodine tartrate (TOT) in its bulk and tablet using HSPiP- and quality by design (QbD)-assisted methods. The HSPiP program predicted several solvents and their right ratios for the mobile phase, followed by simulating the experimental solubility data in various predicted solvents. QbD was used to identify the impact of the composition and the mobile phase flow rate on the peak area and retention time. TOT was estimated using an Agilent TC C18 column employing an optimized mobile phase. The HSPiP shortened the solvent selection time with high reliability, whereas QbD identified critical factors. The optimized composition and process variables were used to develop an analytical method for TOT estimation. Various analytical validation parameters were estimated with constructed linearity of 5–30 μg/mL and a percent recovery yield value of 100.36%. To ensure the reliability of the optimized method, we estimated validation parameters (linearity, specificity, precision, accuracy, robustness, and ruggedness) to comply with the ICH guidelines. Considering the high recovery yield, good regression coefficient, low detection limit, and low noise ratio, the optimized method was accurate and precise with a high degree of specificity, rapid process, and reproducibility for the quantitative estimation of tolterodine from both oral analytes (I and II). The validated method was implemented for pharmacokinetic study in rats for quantitative estimation of the analytes with high accuracy, sensitivity, and reproducibility.

Determination of morphine sulfate anti-pain drug solubility in supercritical CO2 with machine learning method

Accurate solute solubility measuring and modeling in supercritical carbon dioxide (ScCO2) would address the best working conditions and thermodynamic boundaries for material processing with this type of fluid. Theory- and data-driven methods are two general modeling approaches. Using theory-driven methods, the solubility is estimated based on the principles of thermodynamics, while data-driven methods are developed by training the algorithms. Despite acceptance of each of these methods, more experimental solubility data are still needed to promote modeling performances. In this study, for the first time, solubility of morphine sulfate is determined and modeled by a set of 13 semi-empirical (theory-driven) and random forest (data-driven) models. Using a laboratory system with an ultraviolet-visible (UV-Vis) spectroscopy, the experimental solubilities including 48 data points were obtained at different temperatures (308–338 K) and pressures (12–27 MPa). The minimum (0.806 × 10−5) and maximum (5.902 × 10−5) equilibrium mole fractions were observed at working pressures of 12 and 27 MPa, respectively, both at the same temperature of 338 K. It was indicated that random forest model (with AARD% of 1.29%) had an excellent predictive performance against semi-empirical models (with AARD% from 9.33 to 19.76%). The results showed that solute molecular weight had the highest effect on random forest modeling. Using modeling results from Chrastil and Bartle models, total and vaporization enthalpies of dissolution of morphine sulfate in ScCO2 were found to be 35.12 and 59.04 kJ/mole, respectively.

Kinetic modeling of palmitic acid hydrodeoxygenation incorporating phase-equilibria predictions from the GC-PC-SAFT equation of state

In this work, we investigated the phase equilibria and the kinetics of palmitic acid hydrodeoxygenation over Pt/C to produce liquid hydrocarbons as drop-in biofuels. To describe the reaction mixture in detail, the binary interaction parameters of water/hydrogen, water/palmitic acid, water/n-hexadecane, and water/hexadecan-1-ol were estimated for a group contribution model based on the PC-SAFT equation of state using experimental solubility data taken from literature. Kinetic modeling using a power law model based on concentrations, a power law model based on fugacities, and a coupled VLE/power-law model were conducted to evaluate the effects of considering the non-ideality and the phase equilibria of the system. Under the operational conditions studied, the power law model based on concentrations was deemed more suitable to describe the process since it provided a faster implementation and similar outcomes compared to the fugacity-based and the VLE coupled models.

Design of green DES-based aqueous two phase systems for lipolytic enzymes extraction

This study pioneers a novel green and cost-effective separation process using reline deep eutectic solvent (DES) for extracting Thermomyces lanuginosus lipase (TlL) from aqueous solutions. For the first time, it has been shown that various potassium organic salts combined with reline DES can induce phase separation in aqueous solutions of the biodegradable non-ionic surfactant Tergitol 15-S9, presenting a groundbreaking alternative to the banned surfactant Triton X-100. This work uniquely applies three different equations to describe the experimental solubility curves. The selection of reline DES is particularly innovative as it avoids significant deactivation effects with three commercial lipases: Candida antarctica lipases A and B, and TlL, with the latter undergoing a detailed study. This includes an unprecedented analysis of its thermodeactivation kinetics in reline DES aqueous solutions. Additionally, a novel investigation of immiscibility regions at different temperatures, involving comprehensive Tie-Line characterizations (slope and length), preceded the evaluation of lipase extraction. Remarkably, the study demonstrates that optimizing the feed composition to contain higher water concentrations can achieve exceptionally high extraction efficiencies (approximately 90%), suggesting a transformative potential for future applications in real aqueous cultures.

Solubility and thermodynamic analysis of aceclofenac in different {Carbitol + water} mixtures at various temperatures

The solubility and thermodynamic properties of the anti-inflammatory drug aceclofenace (ACF) have been assessed in a range of {2-(2-ethoxyethoxy)ethanol (Carbitol) + water} combinations at temperatures ranging from 298.2 K to 318.2 K and atmospheric pressure of 101.1 kPa. The shake flask method was employed to determine the solubility of ACF, and various models including “van’t Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van’t Hoff models” were used to validate the results. The computational models demonstrated a strong correlation with the experimental ACF solubility data, as indicated by the error values of < 3.0%. In the compositions of {Carbitol + water}, the ACF mole fraction solubility was enhanced by temperature and Carbitol mass fraction. The solubility of ACF in mole fraction was found to be lowest in pure water (1.07 × 10− 6 at 298.2 K), and highest in pure Carbitol (1.04 × 10− 1 at 318.2 K). Based on the positive values of the calculated thermodynamic parameters, the dissolution of ACF was determined to be “endothermic and entropy-driven” in all of the {Carbitol + water} solutions that were studied. It was also observed that enthalpy controls the solvation of ACF in solutions containing {Carbitol + water}. ACF-Carbitol had the strongest molecular interactions in contrast to ACF-water. Based on the results of this study, Carbitol holds significant potential for enhancing the solubility of ACF in water.

Equilibrium Solubility of Sulfadiazine in (Acetonitrile + Ethanol) Mixtures: Determination, Correlation, Dissolution Thermodynamics, and Preferential Solvation

The equilibrium solubility of sulfadiazine (SD, 3) in several {acetonitrile (MeCN) + ethanol (EtOH)} mixtures at nine temperatures from T/K = (278.15 K to 318.15) has been determined by following the shake flask method. SD solubility increased with temperature-arising as well as with the MeCN proportion-increasing in the mixtures. Thus, x3 increased from 7.74 × 10−5 in neat EtOH to 6.20 × 10−4 in neat MeCN at T/K = 298.15. SD solubility was adequately correlated with a second-order multivariate equation as function of both mixtures composition and temperature. Moreover, two models including the Jouyban–Acree and Jouyban–Acree–van’t Hoff models were applied to mathematical SD solubility data modeling in solvent mixtures. The accuracy of each model is investigated by the mean relative deviations (MRD%) of the back-calculated solubility. A full predictive model was provided by training the Jouyban–Acree–van’t Hoff model with only seven experimental solubility data which provided excellent predictions with the MRD% of 3.7 %. All used models show a low MRD% values (< 4.0 %) for the calculated data indicating a good correlation of SD solubility data with the given mathematical models. By means of the van’t Hoff and Gibbs equations, the apparent thermodynamic quantities relative to SD dissolution and mixing processes, namely Gibbs energies, enthalpies, and entropies, were calculated and reported. Apparent dissolution quantities of SD were positive in all cases indicating endothermic and entropy-driven behaviors. A non-linear enthalpy–entropy relationship was observed for SD in the plot of SD dissolution enthalpy vs. Gibbs energy. Observed trend exhibits negative slope in the composition from neat EtOH to the mixture of 0.05 in mass fraction of MeCN indicating entropy-driving mechanism for this SD transfer process. Moreover, variant but positive slopes were found in the composition interval of 0.05 < w1 < 1.00 indicating enthalpy-driving mechanism for these SD transfer processes. Furthermore, the preferential solvation of SD by MeCN or EtOH was analyzed by using the inverse Kirkwood–Buff integrals. Thus, SD is preferentially solvated by EtOH molecules in EtOH-rich mixtures but preferentially solvated by MeCN in MeCN-rich mixtures. In this way, this research expands the literature investigations about the solubility of SD in some non-aqueous cosolvent mixtures conformed by MeCN and other alcohols.

Hansen solubility parameters and quality-by-design oriented optimized cationic nanoemulsion for transdermal drug delivery of tolterodine tartrate

Tolterodine tartrate (TOT) is a selective anti-muscarinic drug to treat urinary urgency and overactive urinary bladder (OAB) occurring in children, renal disease and elderly patients. Oral delivery is associated with several adverse effects. We addressed HSPiP and QbD (quality by design)-oriented TOT loaded cationic nanoemulsions for transdermal delivery. Hansen solubility parameters (HSP) screened excipients based on theoretical solubility whereas, QbD optimized cationic nanoemulsions (CNE-TOT-6). Formulation characteristic parameters were desirable to execute targeted in vitro drug release and ex vivo permeation profiles. In vitro hemolysis was conducted at varied concentrations whereas, histopathological study supported the safety aspect of CNE-TOT6. A comparative bioavailability was carried out in a rat model. Capmul PG8 (CAP), tween 80, and PEG 400 (polyethylene glycol 400) were screened based on HSP and experimental solubility data. QbD suggested optimized content of CAP, tween 80, and PEG 400 to achieve the lowest value of size (184 nm), maximum % entrapment efficiency (87.2 %), high zeta potential (+32.6 mV), optimum viscosity (47.19 cP), and high extrudability (96 %) as compared to its gel. High gel consistency slowed down the drug release and permeation flux as compared to CNE-TOT6 suspension. Hemocompatible CNE-TOT6 increased pharmacokinetic parameters as compared to the control and gel without causing skin toxicity after application. Thus, HSPiP and QbD oriented cationic nanoemulsions are promising carriers to treat overactive urinary bladder.

HSPiP and QbD oriented optimized stearylamine-elastic liposomes for topical delivery of ketoconazole to treat deep seated fungal infections: In vitro and ex vivo evaluations

The study explored stearylamine containing cationic elastic liposomes to improve topical delivery and efficacy of ketoconazole (KETO) to treat deeply seated fungal infections. Stearylamine was used for dual functionalities (electrostatic interaction and flexibility in lipid bilayer). Hansen solubility program (HSPiP) estimated Hansen solubility parameters (HSP) based on the SMILE file and structural properties followed by experimental solubility study to validate the predicted values. Various formulations were developed by varying phosphatidylcholine and surfactants (tween 80 and span 80) concentration. To impart cationic properties, stearylamine (1.0 %) was added into the organic phase. Using quality by design (QbD) method, we optimized the formulations and evaluated for vesicle size, polydispersity index, zeta potential, morphology (scanning electron microscopy), in vitro drug release (%), and ex vivo permeation profiles. Result showed that there is a good correlation (0.65) between HSPiP predicted and actual experimental solubility of KETO in water, chloroform, S80, and tween 80. Spherical OKEL1 showed an established correlation between the predicted and the actual formulation parameters (size, zeta potential, and polydispersity index) (259 nm vs 270 nm, +2.4 vs 0.21 mV, and 0.24 vs 0.27). OKEL1 was associated with the highest value of %EE (83.1 %) as compared to liposomes. Finally, OKEL1 exhibited the highest % cumulative permeation (49.9 %) as compared to DS (13 %) and liposomes (25 %). Moreover, OKEL1 resulted in 4-fold increase in permeation flux as compared to DS which may be attributed to vesicular mediated improved permeation and gel based compensated trans epidermal water loss in the skin. The drug deposition elicited OKEL1 and OKEL1-gel as suitable carriers for maximum therapeutic benefit to treat deeply seated fungal infections.

A comprehensive study of pharmaceutics solubility in supercritical solvent through diverse thermodynamic and hybrid Machine learning approaches

The pharmaceutical industry is increasingly drawn to the research of innovative drug delivery systems through the use of supercritical CO2 (scCO2)-based techniques. Measuring the solubility of drugs in scCO2 at varying conditions is a crucial parameter in this context. In this research, the supercritical solubility of two pharmaceutical ingredients, namely Febuxostat and Chlorpromazine, has been assessed theoretically using various thermodynamic approaches, including PR, SRK, UNIQUAC, and Wilson models. Additionally, hybrid machine learning models of PO-GPR, and PO-KNN were applied to anticipate the supercritical solubility of these medicines. Verification of the accuracy of each model for each pharmaceutical substance is conducted against previously reported experimental solubility data. In the comparison between the SRK and PR models, it is observed that the SRK model displays greater precision in correlating the solubility of both drugs. It consistently achieves a mean Radj value of 0.995 across all cases and mean AARD% values of 14.47 and 9.30 for Febuxostat and Chlorpromazine, respectively. Furthermore, the findings indicate that the UNIQUAC model surpasses the Wilson model in precisely representing the solubility of both medicines. It consistently achieves a mean Radj value higher than 0.985 across both cases and mean AARD% values of 11.39 and 7.08 for Febuxostat and Chlorpromazine, respectively. Additionally, the performance of both hybrid machine learning models proved to be excellent in anticipating the supercritical solubility of both compounds.

Thermodynamic modeling of anticancer drugs solubilities in supercritical CO2 using the PC-SAFT equation of state

In this research, the solubility of anticancer drugs in the supercritical CO2 is modeled using the PC-SAFT equation of state (EoS). Ten anticancer drugs containing Empagliflozin, Sorafenib tosylate, Verapamil, Sodium valproate, Aprepitant, Sunitinib malate, Tamsulosin, Imatinib mesylate, Capecitabine, and Docetaxel are studied to evaluate the model performance. For each component, three temperature-independent model parameters are optimized by the experimental solubility data. The CO2 is modeled as associative molecules with four associating sites and four association sites are considered on anticancer molecules. Therefore, the cross-association between anticancer and CO2 molecules is considered. The average ARD, RMSE, and AAD values of the PC-SAFT EoS for the aforementioned anticancer drugs are obtained 11.45 %, 0.067, and 0.00026 %, respectively. The PC-SAFT EoS results are compared to various types of cubic EoSs and semi-empirical models. The results show that the PC-SAFT EoS with three model parameters can be used as a robust and efficient thermodynamic model to calculate the solubility of complex molecules in supercritical CO2 up to high pressures and temperatures.

In vitro and in silico studies of the inclusion complexation of 8-bromobaicalein with β-cyclodextrins

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically βCD, 2,6-di-O-methyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all βCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMβCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (AL type) between BB and βCDs, in which BB/DMβCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMβCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMβCD for formulating BB in pharmaceutical and medical applications.

Deep Eutectic Solvent + Water System in Carbon Dioxide Absorption.

In the present work, deep eutectic solvents (DESs) were synthesized in a one-step process by heating the hydrogen bond acceptors (HBAs) tetrabutylammonium bromide and tetrabutylphosphonium bromide, along with two hydrogen bond donors (HBDs) ethanolamine and N-methyldiethanolamine, which were mixed in certain molar ratios. This mixture was then mixed with water to form a DES + water system. The densities of the prepared DES + water systems were successfully measured using the U-tube oscillation method under atmospheric pressure over a temperature range of 293.15-363.15 K. The CO2 trapping capacity of the DES + water systems was investigated using the isovolumetric saturation technique at pressures ranging from 0.1 MPa to 1 MPa and temperatures ranging from 303.15 K to 323.15 K. A semi-empirical model was employed to fit the experimental CO2 solubility data, and the deviations between the experimental and fitted values were calculated. At a temperature of 303.15 K and a pressure of 100 kPa, the CO2 solubilities in the DES + water systems of TBAB and MEA, with molar ratios of 1:8, 1:9, and 1:10, were measured to be 0.1430 g/g, 0.1479 g/g, and 0.1540 g/g, respectively. Finally, it was concluded that the DES + water systems had a superior CO2 capture capacity compared to the 30% aqueous monoethanolamine solution commonly used in industry, indicating the potential of DES + water systems for CO2 capture.

Effect of protic surfactant ionic liquids based on ethanolamines on solubility of acetaminophen at several temperatures: measurement and thermodynamic correlation

Absolute qualifications with the application of protic ionic liquids (PILs) and a recognition of the numerous thermophysical features of these materials are required in various processes. Due to the wonderful applications of these compounds and their high potential in the chemical and pharmaceutical industries, there is a particular eagerness to utilize these PILs in drug solubility and delivery area. The aim of this investigation was to explore the solubility of the acetaminophen (ACP) in three PILs base on ethanolamine laurate [(2-hydroxyethylammonium laurate [MEA]La), (bis(2-hydroxyethyl)ammonium laurate [DEA]La), and ( tris(2-hydroxyethyl)ammonium laurate [TEA]La)]. The shake flask method has been employed in this study, and the conditions were set at T = (298.15–313.15) K and atmospheric pressure. Moreover, the experimental solubility data was correlated using a variety of empirical and thermodynamic models, encompassing e-NRTL and Wilson activity coefficient models and the empirical models such as Van’t Hoff-Jouyban-Acree and Modified Apelblat-Jouyban-Acree. Their performance for the system containing [MEA]La follow the trend for activity coefficient models and empirical respectively: the Wilson > e-NRTL and Modified Apelblat–Jouyban–Acree > Van’t Hoff–Jouyban–Acree. On the other hand, [DEA]La and [TEA]La PILs followed slightly different trend for activity coefficient models and empirical respectively: the Wilson > e-NRTL and Van’t Hoff–uyban–Acree > Modified Apelblat–Jouyban–Acree. The Van’t Hoff and Gibbs equations were used to determine the thermodynamic properties of dissolution in the studied systems.

Tolterodine Tartrate Loaded Cationic Elastic Liposomes for Transdermal Delivery: In Vitro, Ex Vivo, and In Vivo Evaluations.

Tolterodine tartrate (TOTA) is a first-line therapy to treat overactive urinary bladder (OAB). Oral delivery causes high hepatic clearance, xerostomia, headache, constipation, and blurred vision. We addressed Hansen solubility parameter (HSP) and Design Expert oriented optimized cationic elastic liposomes for transdermal application. The experimental solubility was conducted in HSPiP predicted excipients to tailor formulations using surfactants, stearylamine, ethanol, and phosphatidylcholine (PC). These were evaluated for formulation characteristics. The optimized OTEL1 and OTEL1-G (gel) were compared against the drug solution (DS) and liposomes. In vitro and ex vivo studies were accomplished to investigate the insights into the mechanistic understanding of TOTA release and permeation ability. Finally, confocal laser scanning microscopy (CLSM) supported ex vivo results. HSP values of TOTA were closely related to tween-80, stearylamine, and human's skin. The size (153nm), %EE (87.6%), and PDI (0.25) values of OTEL1 were in good agreement to the predicted values (161nm, 80.4%, and 0.31) with high desirability (0.963). Spherical and smooth OTEL1 (including OTEL1-G and liposomes) vesicles followed non-Fickian drug release as compared to DS (Fickian) as evidence with n > 0.5 (Korsmeyer and Peppas coefficient). OTEL1 (containing lipid and surfactant as 90mg and 13.8mg, respectively) exhibited 2.6 and 1.8-folds higher permeation flux than DS and liposomes, respectively. Biocompatible cationic OTEL1 was safe and non-hemolytic. OTEL1 was promised as a lead vesicular approach and an alternative to conventional oral therapy to treat OAB in children and advanced age patients.

Configuration rearrangement of squalane induced by carbon dioxide dissolution: A molecular simulation study

Squalane has emerged as a desirable absorbent material for carbon capture, utilization, and storage solutions due to its tunable sorption properties, microscopic structures, and cost-effectiveness in response to the increasing demand. Moreover, a thorough understanding of the fundamental characteristics of hydrocarbons and dissolved gases involved in the Fischer–Tropsch industrial synthesis processes is also essential for researching industrial purification and separation. However, these macromolecules may experience varying degrees of induced alterations in their structural rearrangement when absorbing absorbates, which impacts the performance indicators of squalane. This study examined the solubility characteristics of absorbents made from squalane and their interaction with gaseous CO2 molecules. The perturbed chain statistical associated fluid theory (PC–SAFT) was employed to comprehensively evaluate the macroscopic thermodynamic experimental density and solubility data. Simultaneously, the Monte Carlo (MC) simulation approach was utilized to investigate the rearrangement and swelling features of the squalane chain induced by the presence of CO2 gas in a broad spectrum of temperature and pressure conditions. This work indicated that elevated temperatures increased flexibility in the molecular structure of squalane, leading to a more pronounced spatial dispersion, while higher pressures may lead to spatial homogeneity and enhanced capacity for carrying additional CO2 molecules. The examples and methodologies presented demonstrate the effectiveness of molecular simulations in comprehending absorption–based phenomena at an atomistic and molecular level and offer essential guidance in forecasting the potential for separation, storage, or catalytic.

Solubility behavior and solvation effect of a photomechanical molecular crystal trans-4-chlorocinnamic acid in twelve neat solvents at temperatures from 283.15 to 323.15 K

Solubility of trans-4-chlorocinnamic acid as a photomechanical molecular crystal material in twelve pure solvents (water, ethanol, methanol, n-propanol, isopropanol, n-butanol, isobutanol, acetonitrile, 1,4-dioxane, acetone, methyl acetate and ethyl acetate) were measured from 283.15 to 325.15 K at 101.2 kPa. The results showed that the trans-4-chlorocinnamic acid solubility increased with the temperature, the order is: 1,4-dioxane > acetone > n-butanol > ethanol > n-propanol > isopropanol > isobutanol > methanol > methyl acetate > ethyl acetate > acetonitrile > water. Powder X-ray diffraction pattern (PXRD) and differential scanning calorimetry (DSC) were used to identify and characterize the equilibrated solid phase samples. The solubility behavior and the solute–solvent interaction of trans-4-chlorocinnamic acid in each selected mono-solvent were explored by the empirical solvents polarity parameter (ET(30)), hydrogen bonding, cohesive energy density, molecular structure, and Hansen solubility parameters (HSPs). In addition, the experimental solubility data were correlated by the modified Apelblat model and Yaws model, and the fitting results of this models were all satisfactory. The intermolecular forces were determined through molecular simulations, including Hirshfeld surface (HS) and Molecular Electrostatic Potential Surface (MEPS) analysis. The results showed that hydrogen bond can be formed between trans-4-chlorocinnamic acid and the selected solvents, which can help to further explain the dissolution behavior of trans-4-chlorocinnamic acid in the solvents.

Solubility of curcumin in subcritical water: Experimental data, modeling, and thermodynamic parameters

As an anticancer drug, the mole fraction solubility of curcumin in subcritical water (SBCW) was determined by a static method. Experiments were performed at temperatures between 298.15–423.15 K and a constant pressure of 20 bar. With increasing temperature, the mole fraction of solubility showed a significant increase in the range of 0.03 × 10-6< x 2< 13.22 × 10-6. For the correlation of experimental solubility data, linear, modified Apelblat, NRTL, UNIQUAC, and Wilson thermodynamic models were selected. Among the models, NRTL and modified Apelblat models had a better correlation with the experimental data with MPD% 6.94, 4.68, and RMSD×105 0.07, 0.04, respectively. Also, the thermodynamic functions such as Gibbs free energy, enthalpy, and entropy were calculated for the solubility process of curcumin in SBCW.

Experimental analysis and modeling of aprepitant (an antiemetic drug for chemotherapy) solubility in subcritical water with/without co-solvent

This action described the experimental equilibrium solubility of aprepitant (APT), an antiemetic drug for chemotherapy, in subcritical water (SW) with/without ethanol as co-solvent, acquired through a static method between 298.15 and 393.15 K and 0–15 % (w/w) of ethanol and the constant pressure of 10 bar. The mole fraction of APT was obtained in the range of 0.39×10−4 to 9.10×10−4 while its mole fraction by cosolvent varied from 0.75×10−4 to 22.98×10−4. The obtained results represented the significant effect of solvent temperature on the solubility of APT. For both studied systems, the solubility data was successfully correlated with two well-known semi-empirical temperature-based models, namely the linear and modified Apelblat models. Results from applying statistical criteria exhibited that the modified Apelblat model had the highest accordance with experimental data. Finally, using the obtained correlation results, the apparent thermodynamic analysis including enthalpy, entropy, and Gibbs free energy of dissolution for APT dissolved in SW was obtained.