Harnessing the power of natural deep eutectic solvents (choline chloride/sucrose) and polypropylene glycol in the formation of aqueous biphasic systems and the application of these systems in drug extraction.

In recent times, there has been considerable interest in utilizing aqueous biphasic systems (ABSs) containing natural deep eutectic solvents (NADESs) for the extraction of various substances. In this study, we focused on investigating the phase behavior of ABSs composed of poly(propylene) glycol 400 and NADESs (specifically, choline chloride/sucrose with molar ratios of 2 : 1 and 1 : 1). By analyzing the compositions of tie-lines, it was observed that these ABSs, which consist of four components, exhibit characteristics similar to ternary systems. To examine the influence of molar ratios on phase separation, the binodal model was applied to the obtained binodal data. The NRTL and UNIQUAC models were employed to establish correlations for the tie-lines. Moreover, we examined the extraction capabilities of the aforementioned ABSs for three commonly used drugs: diclofenac potassium, acetaminophen, and salicylic acid. To assess the efficiency of extraction, partition coefficients and extraction efficiencies were calculated for each drug. The results revealed that the extraction efficiency of these drugs into the polymer-rich top phase is dependent on their hydrophobicity. Furthermore, we employed the Diamond-Hsu equation, along with its modified version, to establish correlations between the experimental partition coefficients of the drugs and NADES overall concentrations.

Thermodynamic studies of solute-solute and solute-solvent interactions in ternary aqueous systems containing {betaine + PEGDME250} and {betaine + K3PO4 or K2HPO4} at 298.15 K.

In this work, to evaluate solute-solute, solute-solvent and phase separation in aqueous systems containing {betaine + poly ethylene glycol dimethyl ether with molar mass 250 g mol-1 (PEGDME250)}, {betaine + K3PO4} and {betaine + K2HPO4}, first water activity measurements were made at 298.15 K and atmospheric pressure using the isopiestic technique. The water iso-activity lines of these three systems were obtained which have positive deviations from the semi-ideal solutions. This suggests that betaine-polymer and betaine-K3PO4 or betaine-K2HPO4 interactions are unfavorable; and these mixtures may form aqueous two-phase systems (ATPSs) at certain concentrations. Indeed the formation of ATPSs was observed experimentally. Then, osmotic coefficient values were calculated using the obtained water activity data; and, using the polynomial method the solute activity coefficients were determined. Using these activity coefficients, the transfer Gibbs energy ([Formula: see text]) values were calculated for the transfer of betaine from aqueous binary to ternary systems consisting polymer (PEGDME250) or salts (K3PO4 and K2HPO4). The obtained positive [Formula: see text] values again indicated that there is unfavorable interaction between betaine and these solutes. Finally, the volumetric and ultrasonic studies were made on these systems to examine the evidence for the nature of interactions between betaine and the studied salts or polymer.

Solubility of hesperidin drug in aqueous biodegradable acidic choline chloride-based deep eutectic solvents.

Important efforts have been made over the past years to improve the drug acts, which leads to the discovery of novel drug preparations and delivery systems. The selection of suitable green solvents for novel drug discovery and drug delivery depends on a molecular-level understanding of the interaction between drug molecules and the solvents. Deep eutectic solvents (DESs) are already used in sustainable extraction methods of natural products for their very high solvent power, high chemical and thermal stability, non-toxicity, and non-flammable. The thermodynamic investigation provides deep and complete knowledge of interactions and the choice of appropriate and suitable production compounds in pharmaceutical fields. Particularly, the analysis of drugs+DESs in aqueous media is a central issue in many types of research. This research is aimed to determine hesperidin (HES) solubility in water and DES solvents [choline chloride/citric acid (ChCl/CA), choline chloride/oxalic acid (ChCl/OA), choline chloride/malonic acid (ChCl/MA), and choline chloride/lactic acid (ChCl/LA)] at temperature range (298.15-313.15 K). Furthermore, the measured solubility data of HES in studied aqueous DESs solutions was fitted by models of Van't Hoff-Jouyban-Acree and Modified Apelblat-Jouyban-Acree. Finally, the Hansen solubility parameters as thermodynamic aspect for analyzing the dissolution processes for the four investigated aqueous DESs solutions were estimated.

Liquid-liquid equilibrium measurements and computational study of salt-polymer aqueous two phase system for extraction of analgesic drugs.

In recent decades, aqueous two phase systems have gained a lot of attention for extraction of different materials. In this work, an aqueous two phase system was made by polyethylene glycol 600 and potassium hydroxide and phase diagram were determined for this system. The experimental binodal data were described using two empirical nonlinear three parameter expressions developed by Merchuk and Zafarani-Moattar. The consistency of the experimental tie-line data was determined by utilizing the Othmer-Tobias, Bancraft, and Setschenow correlations. Also, the extraction of two analgesic drugs, namely ibuprofen and acetaminophen were investigated by the mentioned ATPS. For this purpose, partition coefficients and extraction efficiencies of each drug were calculated. The trend of extraction efficiencies indicated that the responsibility of extraction of the mentioned drugs into the polymer-rich top phase is related to their hydrophobicity. The Diamond-Hsu equation and its modified version were used to correlate the drugs experimental partition coefficients. Furthermore, the interaction of mentioned drugs with polyethylene glycol was investigated employing quantum computing techniques based upon density functional theory (DFT). These results were in good agreement with the trend of extraction efficiencies of studied drugs.

Deep eutectic solvents for antiepileptic drug phenytoin solubilization: thermodynamic study.

Thermodynamic investigations provide information about the solute-solvent interactions in the selection of the proper solvent for different fields of pharmaceutical sciences. Especially, the study of antiepileptic drugs in solutions (ethanol/co-solvent) has been a subject of interest owing to their effect in the systems using interaction with a number of important biological membranes. This work focuses on the measurement of density and speed of sound of the phenytoin (PTH) in ethanol/deep eutectic solvents (choline chloride:ethylene glycol, and choline chloride:glycerol) solutions as the innovative class of green solvents at temperature range (288.15 to 318.15) K. It was determined Hansen solubility parameters for assessment of PTH interactions in the solvent media. Some thermophysical parameters including apparent molar volumes Vϕ, apparent molar isobaric expansion [Formula: see text], and Hepler's constant, apparent molar isentropic compressibility κφ were obtained and calculated using these data. To correlate  the Vϕ and κφ values, the Redlich-Meyer equation was used to calculate the number of quantities containing standard partial molar volume and partial molar isentropic compressibility. Finally, [Formula: see text] values showed a strong interaction between PTH and solvent (ethanol/DES (ChCl:EG)). The thermodynamic analysis of the studied system also plays a crucial role in the pharmaceutical industry.

Thermodynamic Properties of Ternary Systems Containing (LiCl and LiBr) + Propylene Carbonate + Ionic Liquid (1-Alkyl-3-methylimidazolium Thiocyanate).

The development of the Li-ion battery Industry in a green way is crucial for human beings' future. Ionic liquids (ILs) are green cosolvents that could be applied in Li-ion battery electrolytes. A thermodynamic study has been carried out for a Li-ion electrolyte (propylene carbonate (PC) + LiCl and LiBr) in the presence of IL 1-alkyl-3-methylimidazolium thiocyanate [RMIM][SCN] (R = butyl, hexyl, and octyl). The studied thermodynamic properties were density, speed of sound, apparent molar volume, and compressibility. The effect of ILs in propylene carbonate (PC) has been investigated under atmospheric pressure at T = (288.15-318.15) K. Also, a microscopic approach using scaled particle theory has been implemented. The solvation effect of lithium halides, LiX (X = Cl-, Br-), on the volumetric and compressibility properties of the ILs has been studied at 298.15 K. The results show that [OMIM][SCN] has the strongest interactions with PC in the studied ILs and these interactions are more weakened with the addition of LiBr than LiCl. According to the partial molar compressibility results, the systems containing [OMIM][SCN] could be used under pressure more beneficially than other systems from the thermodynamic aspect of view.

How Different Electrolytes Can Influence the Aqueous Solution Behavior of 1-Ethyl-3-Methylimidazolium Chloride: A Volumetric, Viscometric, and Infrared Spectroscopy Approach.

The density, sound velocity, and viscosity of 1-ethyl-3-methylimidazolium chloride [C2mim]Cl in pure water and aqueous solutions of some electrolytes such as potassium chloride, potassium carbonate, and potassium phosphate (weight fraction of salt fixed at w s = 0. 11) have been measured over a wide range of temperatures from 298.15 to 318.15 K. The obtained experimental data have been used to compute various volumetric, compressibility, and viscometric parameters, e.g., apparent molar properties, limiting apparent molar and transfer properties. The co-sphere overlap model was employed to describe the dominant intermolecular interactions in the ternary solutions. Additionally, the structure making/breaking nature of the [C2mim]Cl in the ternary solutions has been discussed in terms of Hepler's constant and the temperature derivative of viscosity B-coefficient (dB/dT). The activation free energy of solvent and solute, activation enthalpy, and activation entropy have been calculated by the application of transition state theory. The calculated parameters have been interpreted in the sense of solvent-solute and solute-solute interactions. The Fourier transform infrared (FTIR) studies also have been done for the studied systems. Volumetric, acoustic, viscometric, and spectroscopic studies can render some evidence and help to understand the aqueous solution behavior of ionic liquids.

Effect of ionic liquids 1-octyl-3-methyl imidazolium bromide or 1-octyl-3-methyl imidazolium chloride on thermophysical properties and taste behavior of sucrose in aqueous media at different temperatures: Volumetric, compressibility and viscometric properties.

The thermophysical properties and taste behavior of sucrose in aqueous ionic liquids {1-octyl-3-methyl imidazolium bromide and 1-octyl-3-methyl imidazolium chloride} solutions have been studied via volumetric, compressibility and viscometric properties at T = (288.15, 298.15, 308.15 and 318.15) K. The positive values of transfer volume and transfer partial molar isentropic compression indicated predominance of ionic-hydrophilic interactions in these systems. The calculated hydration number for sucrose demonstrated that dehydration of sucrose occurs in presence of both studied ionic liquids. Further, the effect of studied ionic liquids on the taste behaviour of sucrose has been discussed from ASV and ASIC parameters. Furthermore, interaction volume, Vint, and cavity volume, Vcav, have been computed from scaled particle theory (SPT).

Effect of Tetrabutylammonium Bromide-Based Deep Eutectic Solvents on the Aqueous Solubility of Indomethacin at Various Temperatures: Measurement, Modeling, and Prediction with Three-Dimensional Hansen Solubility Parameters.

Deep eutectic solvents (DESs) have recently been getting a great deal of attention in many fields of science and technology. The objective of this study was to peruse the solubility of indomethacin (IMC) as sparingly soluble drug in some tetrabutylammonium bromide (TBAB)-based DESs (TBAB/ethylene glycol and TBAB/glycerol). The shake flask method has been employed in this study at temperature ranges T = (298.15-313.15) K and atmospheric pressure (pP = 86.6 kPa). The results showed that the solubility of IMC in TBAB/ethylene glycol system was obtained approximately 17,000-fold more than its solubility in water. The solubility data were accurately correlated by the famous local composition activity coefficient models including e-NRTL and UNIQUAC. It was also our aim to evaluate Hansen solubility parameters in IMC solubility prediction. These parameters can help to predict the solvent performance during the manufacturing processes and will be useful in guessing solvent behavior in many other fields of effort. The experimental and the Hansen solubility parameters results are very well matched. In addition, the apparent thermodynamic properties of dissolution and mixing were studied in these solutions based on Van't Hoff and Gibbs equations.

Study of naproxen in some aqueous solutions of choline-based deep eutectic solvents: Solubility measurements, volumetric and compressibility properties.

Naproxen (NAP) is a widely used drug for the treatment of pain and inflammatory conditions. However, there is not the physicochemical information about this drug such as solubility, volumetric and compressibility properties in the presence of deep eutectic solvents (DES) as a new class of green solvents to overcome the low solubility of drugs. In this work, the solubility of NAP is studied in the solutions containing some choline chloride (ChCl) based DES at temperature ranges (298.15-313.15) K. The results indicate that the solubility increases with increasing the concentration of DES and temperature and DES containing malonic acid is the proper co-solvent. The experimental solubility values were correlated by the e-NRTL, Wilson and UNIQUAC models. In addition, the complex interactions between the components in the systems should be elucidated, therefore, the thermodynamic properties including volumetric and compressibility properties have been investigated using density and speed of sound measurements at T = 298.15 K. According to calculated thermodynamic parameters, strong interactions between NAP and DESs are observed which is in agreement with obtained solubility data.

Solubility, volumetric and compressibility properties of acetaminophen in some aqueous solutions of choline based deep eutectic solvents at T=(288.15 to 318.15) K.

Deep eutectic solvents (DESs) as a new class of green solvents have been used to overcome the low solubility of drugs during the recent years. In this work, the effect of some DESs containing choline chloride as hydrogen bond acceptor and urea, oxalic acid and malonic acid as hydrogen bond donors have been studied on acetaminophen (ACP) solubility at temperature ranges (298.15 to 313.15) K. The results indicate that the solubility of ACP increase with increasing concentration of DES and at higher temperatures and the DES containing malonic acid have a greater impact on the solubility of acetaminophen. The solubility data were correlated by the modified Apelblat, λh (Buchowski) and Yalkowsky models which Apelblat model is more consistent with experimental data. In addition, to elucidate the interactions between the components, the thermodynamic properties including volumetric, compressibility properties have been investigated using density and speed of sound measurements at T=(288.15 to 318.15K). The calculated thermodynamic parameters values confirm the strong solute - solvent interactions between ACP - DESs that is in agreement with solubility data.

A new aqueous biphasic system containing polypropylene glycol and a water-miscible ionic liquid.

In this work, we proposed a novel aqueous biphasic system (ABS) composed of polypropylene glycol P400 (PPG P400) and hydrophilic ionic liquids (IL), 1-alkyl-3-methylimidazolium bromide (alkyl = ethyl or butyl), forming an upper polymer-rich phase and a lower IL-rich phase at ambient temperature. This new ABS can present interesting characteristics shared by ILs and polymers such as low volatility, good solvation ability, tunable physical properties, and high design capacity for achieving task-specific phase components to enhance the partitioning of target species. Ternary phase diagram of the novel ABS formed by PPG 400 and [C(2) mim]Br in water was measured at T = 298.15 K. Factors affecting the binodal curves such as the cation side alkyl chain length and the temperature were also evaluated. The results were successfully interpreted in terms of the kosmotropic/chaotropic nature of ILs. Furthermore, the phase behavior of the PPG-[C(2) mim]Br ABS is described by the NRTL model. Finally, the extraction potential of the proposed ABS was evaluated through its application to the extraction of the essential amino acids such as L-tryptophan and L-tyrosine. The partition coefficients here obtained demonstrated the fine potential of the proposed ABS for biomolecules separation.

Partitioning of amino acids in the aqueous biphasic system containing the water-miscible ionic liquid 1-butyl-3-methylimidazolium bromide and the water-structuring salt potassium citrate.

In biotechnology, extraction by means of aqueous biphasic systems (ABS) is known as a promising tool for the recovery and purification of bio-molecules. Over the past decade, the increasing emphasis on cleaner and environmentally benign extraction procedures has led to enhanced interest in the ABS containing ionic liquids (ILs)-a new class of non-volatile alternative solvents. ABS composed of the hydrophilic IL {1-butyl-3-methylimidazolium bromide ([C4 mim]Br)} and potassium citrate-which is easily degraded-represents a clean media to green separation of bio-molecules. In this regard, here, the extraction capability of this ABS was evaluated through its application to the extraction of some amino acids. To gain an insight into the driving forces of amino acid partitioning in the studied IL-based ABS, the distribution of five model amino acids (L-tryptophan, L-phenylalanine, L-tyrosine, L-leucine, and L-valine) at different aqueous medium pH values and different phase compositions was investigated. The studies indicated that hydrophobic interactions were the main driving force, although electrostatic interactions and salting-out effects were also important for the transfer of the amino acids. Moreover, based on the statistical analysis of the driving forces of amino acid partitioning in the studied IL-based ABS, a model was established to describe the partition coefficient of three model amino acids, L-tryptophan, L-phenylalanine, and L-valine, and employed to predict the partition coefficient of two other model amino acids, L-tyrosine and L-leucine.