In this study, the solubility of mesalazine was investigated in binary solvent mixtures of poly ethylene glycols 200/600 and water at temperatures ranging from 293.2K to 313.2K. The solubility of mesalazine was determined using a shake-flask method, and its concentrations were measured using a UV-Vis spectrophotometer. The obtained solubility data were analyzed using mathematical models including the van\'t Hoff, Jouyban-Acree, Jouyban-Acree-van\'t Hoff, mixture response surface, and modified Wilson models. The experimental data obtained for mesalazine dissolution encompassed various thermodynamic properties, including ΔG°, ΔH°, ΔS°, and TΔS°. These properties offer valuable insights into the energetic aspects of the dissolution process and were calculated based on the van\'t Hoff equation.

In this study, both practical and theoretical aspects of the solubility of edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The solubility of edaravone in some media, including water, can be limited, which creates the need for new efficient and environmentally safe solvents. The solubility of EDA was measured spectrophotometrically and the complex intermolecular interactions within the systems were studied with the COSMO-RS framework. Of the four studied DES systems, three outperformed the most efficient classical organic solvent, namely dichloromethane, with the DES comprising choline chloride and triethylene glycol, acting as hydrogen bond donor (HBD), in a 1:2 molar proportion yielding the highest solubility of EDA. Interestingly, the addition of a specific amount of water further increased EDA solubility. Theoretical analysis revealed that in pure water or solutions with high water content, EDA stacking is responsible for self-aggregation and lower solubility. On the other hand, the presence of HBDs leads to the formation of intermolecular clusters with EDA, reducing self-aggregation. However, in the presence of a stoichiometric amount of water, a three-molecular EDA-HBD-water complex is formed, which explains why water can also act as a co-solvent. The high probability of formation of this type of complexes is related to the high affinity of the components, which exceeds all other possible complexes.

Organic solvents are hazardous and should be replaced with less harmful alternatives. When developing a new formulation for a medicine with low aqueous solubility, improving its solubility might be a significant difficulty. According to the mixed solvency concept, a novel concept of solubilization, the solubility of poorly soluble drugs can be increased by dissolving them in a concentrated solution comprising various substances. Methods commonly used to improve solubility include complexation, pH modification, salt formation, hydrotropy, cosolvency, and micelle solubilization. By reducing the concentration of specific solubilizers, this method can be used to reduce the toxicity of solubilizers in various formulations of poorly soluble medicines. This review aims to provide scientists with a fresh concept for enhancing medication solubility. The benefits and drawbacks of currently available green solvents have been analyzed as potential replacements for traditional solvents. Some examples of these solvents are bio-based solvents like ethanol, methanol, and cyrene; d-limonene; deep eutectic solvents such as ionic liquids and natural deep eutectic solvents; supercritical fluids; subcritical water; surfactant-based solutions like hydrotopes and supramolecular solvents; and deep eutectic solvents like cyrene.

Influence of the cosolvent on the sorption of organic acids on biochar has not been well understood. For this purpose, the sorption (log Km, L kg-1) of three aromatic acids (benzoic acid (BA, pKa = 4.20), 1-naphthoic acid (1-NAPA, pKa = 3.70), and 9-anthroic acid (9-ANTA, pKa = 3.65) was evaluated as a function of methanol volume fraction (fc = 0.0, 0.25, and 0.5), liquid pH (2.5 and 7.0), ionic composition (CaCl2 and KCl) and ionic strength (0.005 M, 0.5 M, and 1 M CaCl2). A giant Miscanthus-derived biochar (ZPC of 2.86) was used as the sorbent. For all solutes, the sorption coefficients (log Km) measured at pH 2.5 (i.e., pH < pKa) tended to decrease with increasing fc, as expected from the cosolvency model, while the result obtained at pH 7.0 was not fully explained by the same model. The log Km of 1-NAPA in the CaCl2 system was always greater than in the KCl system (p < 0.05) and the impact became pronounced at high pH (>pKa) with increasing fc. Increasing the Ca2+ concentration at fc = 0.0 (from 0.005 M to 1 M) enhanced the value by 0.32 log unit of Km. These phenomena indicate a significant role of dissolved Ca2+ in the liquid phase, most likely due to the formation of cation bridges between aromatic carboxylates and the biochar surface (i.e., [R-COO--Ca2+]-{Biochar-}). A decrease in the dielectric constant of the methanol mixture could fortify the formation of this bridge. Regardless of the degree of cosolvency power (σ), as the number of aromatic rings of solutes increases, Km decreases in the order BA > 1-NAPA > 9-ANTA, where fc = 0.0. In conclusion, the sorption potential of biochar can be significantly weakened by increasing pH and fc, and in the absence of a divalent cation.

Low water solubility is the main hindrance in the growth of pharmaceutical industry. Approximately 90% of newer molecules under investigation for drugs and 40% of novel drugs have been reported to have low water solubility. The key and thought-provoking task for the formulation scientists is the development of novel techniques to overcome the solubility-related issues of these drugs. The main intention of present review is to depict the conventional and novel strategies to overcome the solubility-related problems of Biopharmaceutical Classification System Class-II drugs. More than 100 articles published in the last 5 years were reviewed to have a look at the strategies used for solubility enhancement. pH modification, salt forms, amorphous forms, surfactant solubilization, cosolvency, solid dispersions, inclusion complexation, polymeric micelles, crystals, size reduction, nanonization, proliposomes, liposomes, solid lipid nanoparticles, microemulsions, and self-emulsifying drug delivery systems are the various techniques to yield better bioavailability of poorly soluble drugs. The selection of solubility enhancement technique is based on the dosage form and physiochemical characteristics of drug molecules.

Hydrogels are attractive materials not only for their tremendous applications but also for theoretical studies as they provide macroscopic monitoring of the conformation change of polymer chains. The pioneering theoretical work of Dusek predicting the discontinuous volume phase transition in gels followed by the experimental observation of Tanaka opened up a new area, called smart hydrogels, in the gel science. Many ionic hydrogels exhibit a discontinuous volume phase transition due to the change of the polymer-solvent interaction parameter χ depending on the external stimuli such as temperature, pH, composition of the solvent, etc. The observation of a discontinuous volume phase transition in nonionic hydrogels or organogels is still a challenging task as it requires a polymer-solvent system with a strong polymer concentration dependent χ parameter. Such an observation may open up the use of organogels as smart and hydrophobic soft materials. The re-entrant phenomenon first observed by Tanaka is another characteristic of stimuli responsive hydrogels in which they are frustrated between the swollen and collapsed states in a given solvent mixture. Thus, the hydrogel first collapses and then reswells if an environmental parameter is continuously increased. The re-entrant phenomenon of hydrogels in water-cosolvent mixtures is due to the competitive hydrogen-bonding and hydrophobic interactions leading to flow-in and flow-out of the cosolvent molecules through the hydrogel moving boundary as the composition of the solvent mixture is varied. The experimental results reviewed here show that a re-entrant conformation transition in hydrogels requires a hydrophobically modified hydrophilic network, and a moderate hydrogen-bonding cosolvent having competitive attractions with water and polymer. The re-entrant phenomenon may widen the applications of the hydrogels in mechanochemical transducers, switches, memories, and sensors.

This study aimed to provide a rational experimental design to collect a minimum number of experimental data points for a drug dissolved in a given binary solvent mixture at various temperatures, and to describe a computational procedure to predict the solubility of the drugs in any solvent composition and temperature of interest. We gathered available solubility data sets from papers published from 2012 to 2016 (56 data sets, 3488 data points totally). The mean percentage deviations (MPD) used to check the accuracy of predictions was calculated by Eq. 10. Fifty-six datasets were analyzed using 8 training data points which the overall MPD was calculated to be 15.5% ± 15.1%, and for 52 datasets after excluding 5 outlier sets was 12.1% ± 8.9%. The paired t test was conducted to compare the MPD values obtained from the models trained by 7 and 8 training data points and the reduction in prediction overall MPD (from 17.7% to 15.5%) was statistically significant (p < 0.04). To further reduction in MPD values, the computations were also conducted using 9 training data points, which did not reveal any significant difference comparing to the predictions using 8 training data points (p > 0.88). This observation revealed that the model adequately trained using 8 data points and could be used as a practical strategy for predicting the solubility of drugs in binary solvent mixtures at various temperatures with acceptable prediction error and using minimum experimental efforts. These sorts of predictions are highly in demand in the pharmaceutical industry.

Ion cross-linking in situ gels are novel liquid sustained-release drug delivery systems. These systems are unsuitable for poorly water-soluble drugs such as the novel antidiabetic drug mitiglinide calcium (MTG). Thus, our goal was to assess the possibility of using cosolvency approach in formulating gastroretentive in situ gel of the short half-life MTG to simultaneously enhance its bioavailability and sustain its release. MTG in situ gel formulations were developed using propylene glycol as a cosolvent to dissolve MTG in the polymer solution, followed by characterization of viscosity, gel strength, floating ability, and in vitro MTG release and phramacokinetics evaluation. The optimized formulation (composition: 1% gellan gum, 0.75% sodium alginate, 0.75% calcium carbonate, and 7.5% propylene glycol) exhibited reasonable viscosity but on introduction into simulated gastric fluid, it formed firm gel that floated within seconds over the surface and remained buoyant for 24 h. The formula exhibited in vivo sustained release manner of MTG over 24 h and improved the bioavailability of the drug. Thus, cosolvency presents a promising approach to deliver hydrophobic drugs in sustained-release liquid formulations. These formulations will improve diabetic patients\' compliance by eliminating the necessity of frequent dosing with a better disease management.

The sorption of naphthalene (NAP) and 1-naphthoic acid (1-NAPA) onto giant Miscanthus-derived biochar was investigated in methanol volume fractions (fc) of 0-0.6 as a function of ionic composition (5mM CaCl2 and 10mM KCl) and liquid pH (2 and 7). The sorption onto biochar was nonlinear with 0.42≤N≤0.95; thus, a concentration-specific sorption constant (Km) was compared. The Km log linearly decreased with increasing fc, except for 1-NAPA from a CaCl2 mixture at pH7. Isotherm data was fitted with a cosolvency sorption model through which the slope (ασ) of the inverse log linear Km-fc plot and empirical constant (α) were obtained. NAP sorption was well described by the cosolvency model with the α value being 0.41-0.53, indicating a methanol-biochar interaction favoring more sorption than the cosolvency based prediction. In particular, the slope (ασ) of 1-NAPA was lower than that of NAP, indicating less reduction of 1-NAPA sorption (i.e., lower α value) by methanol. In comparison with other sorbents, the α value was approximately intermediate between a humic substance and kaolinite clay. An analysis of FT-IR spectra suggested the transformation of O-containing functional groups by methanol, which will subsequently boost the π-π interaction between an organic solute and biochar. Moreover, Ca2+-induced sorption between anionic 1-NAPA and a negatively charged biochar surface was also fortified in the methanol mixture. The results revealed unexplored cosolvent effects on organic solute sorption onto biochar and identified the hydrophobic and hydrophilic sorption moieties of biochar as affected by the cosolvent.

Applicability of cosolvency model for describing the sorption of organic acids to humic substance was investigated by analyzing dataset of sorption (K m) and solubility (S m) of selected solutes (benzoic acid, 1-naphthoic acid, 2,4-dichlorophenoxyacetic acid, and 2,4,6-trichlorophenol (2,4,6-TCP)) as a function of pH(appCME) (apparent pH of liquid phase) and f c (methanol volume fractions). For all solutes, the K m decreased with f c with the K m reduction being less than the S m-based prediction. The slope of log K m-f c plot in the three organic carboxylic acids was well correlated with their cosolvency power, whereas the data of organic phenolic acid (2,4,6-TCP) was placed above the trend, indicating the different actions of functional groups. The occurrence of Ca(2+) bridge between carboxylate and negatively charged humic surface may explain this phenomenon. Normalizing the K m to the corresponding S m (α\' = K m/S m) was not in unity over the pH(app)-f c range but decreased with f c, indicating a possible structural modification of sorption domain favoring extra sorption. For a given solute, the α\' of neutral species was always greater than that of anionic species, showing that extra interaction will be likely at pH(app) cosolvency model.