Cosolvent Systems Research Articles

Preformulation and Long-Term Stability Studies of an Optimized Palatable Praziquantel Ethanol-Free Solution for Pediatric Delivery.

To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5-10 mg/kg), which since it is only available as tablets, hinders its administration to pediatric patients. Praziquantel is a poorly water-soluble drug which represents a challenge for its formulation in solution, particularly for the pediatric population. Thus, this study aimed to develop a palatable solution for praziquantel using pharmaceutical-accepted co-solvent systems. A design of experiments approach was applied to identify the optimal conditions for achieving a suitable amount of praziquantel in solution using co-solvent mixtures. Thus, praziquantel solubility increased from 0.38 up to 43.50 mg/mL in the optimized system. A taste masking assay in healthy human volunteers confirmed a successful reduction of drug bitterness after the addition of selected flavors and a sweetener. Stability studies were also conducted at different temperatures (4, 25, and 40 °C) for 12 months Even though the presence of the three known impurities of praziquantel was observed, their amounts never exceeded the acceptance criteria of the USP. Thus, this novel approach should be considered a valuable alternative for further preclinical studies considering the high prevalence of this infection worldwide.

Effects of various acid catalysts in dimethyl isosorbide/water co-solvent system for lignocellulosic biomass pretreatment

Novel organosolv pretreatments of biomass using biobased green solvents have attracted increasing attention to realize sustainable biorefinery. We have demonstrated that the feasibility of dimethyl isosorbide/water co-solvent in fractionating lignocellulosic biomass (Eucalyptus) for multiple products under a mild condition (120 °C, 60 min). To take a further step towards revealing the effects of catalysts, we explored various Brønsted (e.g., H2SO4, HCl, and p-TsOH), Lewis acid catalysts (e.g., AlCl3 and FeCl3) and their combinations in this co-solvent system. An interesting finding was that the delignification efficiency of AlCl3 was lower than that of H2SO4 (69.9% vs 91.2%), while the cellulose conversion efficiency of the pretreated pulp was similar (∼80%). It is hypothesized that the presence of Al3+ could inhibit the binding of lignin to cellulase, which was supported by the quantum chemistry calculations. Results revealed the presence of cation− π interactions between Al3+ and lignin with interaction energy (ΔE) was 1022.04 kJ/mol and 1003.04 kJ/mol for S and G type of lignin, respectively. In addition, the pretreatment with H2SO4 -AlCl3 co-catalyst could achieve a high lignin removal efficiency of 93.0% and almost complete enzymatic hydrolysis of obtained cellulose pulp (∼100%). This research demonstrated that the co-catalyst strategy effectively improved the overall performance of the solvent-based biorefinery.

Fluorinated ether-based co-solvent electrolytes for lithium-metal batteries: High ionic conductivity and suppressed dissolution of fragmented anions

Advanced electrolyte solutions for lithium (Li) metal batteries have been developed to improve their comparability with Li electrodes and enhance high oxidative stability. While the solvation structures of Li+ are critical for determining the quality of the solid electrolyte interphase (SEI) layer and cyclability, there is limited understanding of these correlations for co-solvent systems and long-term cycles. Herein, we investigate the role of fluorinated ether-based co-solvents consisting of 2,2,3,3-tetrafluoro-1,4-dimethoxylbutane (FDMB) and 1,2-diethoxyethane (DEE) with 1 M lithium bis(trifluoromethanesulfonyl)imide (LiFSI). FDMB exhibits high oxidative stability and low flammability, and the addition of DEE improves ionic conductivity by sharing Li+ coordination with FDMB. SEI formation is derived from FSI−. Notably, increasing the DEE volume ratio promotes lithium fluoride (LiF) deposition and dissolution of fragmented FSI− into the electrolyte solution. FDMB inhibits such dissolution and enhances the formation of lithium nitride (Li3N) and lithium oxide (Li2O) in the SEI. Thus, the DEE/FDMB co-solvents complemented the weaknesses of the two solvents and offer the low SEI resistance. It explains optimal cycling performance for Li|Li and Li|LiFePO4 cells with 1:6 DEE/FDMB with 1 M LiFSI compared to that of the single DEE and FDMB.

Ethanol-free Cross-Linking of Alginate Nanofibers Enables Controlled Release into a Simulated Gastrointestinal Tract Model.

The use of alginate nanofibers in certain biomedical applications, including targeted delivery to the gut, is limited because an ethanol-free, biocompatible cross-linking method has not been demonstrated. Here, we developed water-stable, alginate-based nanofibers by systematically exploring post-electrospinning cross-linking approaches that used calcium ions dissolved in (1) a glycerol/water cosolvent system and (2) acidic, neutral, or basic aqueous solutions. Scanning electron microscopy proved that the fibers cross-linked in a glycerol cosolvent or pH-optimized solutions had maintained the same morphology as the ethanol-based literature control. Notably, cross-linked fibers were generally smaller in diameter than the as-spun fibers due to both chemical interactions and mass loss during cross-linking, which was supported by mass measurements, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. During stability tests wherein the cross-linked fibers were exposed to three aqueous solutions, the cross-linked fibers were stable in water and acid buffer yet swelled in phosphate buffer saline, making them useful scaffolds for pH-controlled release applications. Proof-of-concept release experiments were conducted using a simulated gastrointestinal tract model. As desired, the cargo remained encapsulated within the cross-linked nanofibers when exposed to an acidic solution that modeled the stomach. Upon exposure to a solution that mimicked the intestines, the cargo was released. We suggest that these cross-linked, alginate-based nanofiber mats hold the potential to be broadly used in biomedical and environmental applications.

Investigating how the dye colour is impacted when chemically separating polyester-cotton blends

Blended textile fabrics with dyed cotton and polyester (PET) fibres intimately mixed are extensively used in the textile industry. Separating and recycling these blends cannot be performed by conventional mechanical or chemical recycling processes, and this is contributing significantly to the global textile waste problem. Here we demonstrate an approach to separate coloured cotton and polyester blends, and the dye is retained in the separated polyester and cotton components. The separation was achieved via chemical dissolution of cotton using a co-solvent system of ionic liquid and dimethyl sulfoxide, from which regenerated cellulose fibres could be directly wet spun. The polyester component was left intact and recovered via filtration. The recovered products were characterised for thermal, chemical, mechanical, colour strength, and morphological properties.

Effect of Solvent on Convectively Driven Silica Particle Assembly: Decoupling Surface Tension, Viscosity, and Evaporation Rate

The process of convectively self-assembling particles in films suffers from low reproducibility due to its high dependency on particle concentration, as well as a variety of interactions and physical parameters. Inhomogeneities in flow rates and instabilities at the air-liquid interface are mostly responsible for reproducibility issues. These problems are aggravated by adding multiple components to the dispersion, such as binary solvent mixtures or surfactant/polymer additives, both common approaches to control stick-slip behavior. When an additive is used, not only does it change the surface tension, but also the viscosity and the evaporation rate. Worse yet, gradients in these three properties can form, which then lead to Marangoni currents. Here, we use a series of alcohols to study the role of viscosity independently of other solvent properties, to show its impact on stick-slip behavior and interband distances. We show that mixtures of glycerol and alcohol or poly(acrylic acid) and alcohol lead to more complex patterning. Marangoni currents are not always observed in co-solvent systems, being dependent on the rate of solvent evaporation. To produce homogeneous particle assemblies and control stick-slip behavior, gradients must be avoided, and the surface tension and viscosity need both be carefully controlled.

Evolution of the Cellulose Microfibril through Gamma-Valerolactone-Assisted Co-Solvent and Enzymatic Hydrolysis

Biomass recalcitrance during deconstruction remains a key bottleneck to affordable biomass processing technologies. A clear connection between the cell wall structure and biomass deconstruction is necessary to understand how lignocellulosic material is broken down to valuable monomeric components. Here, we monitor changes in the cellulose microfibril domains of poplar, sorghum, and switchgrass throughout gamma-valerolactone (GVL)–water co-solvent pretreatment and enzymatic hydrolysis using solid-state 13C cross-polarization magic angle spinning nuclear magnetic resonance spectroscopy (CP/MAS 13C-NMR) and wide-angle X-ray scattering (WAXS). Spectral fitting of NMR peaks corresponding to different cellulose microenvironments at the C4 carbon center suggests that a mildly acidic GVL–water co-solvent pretreatment of poplar leads to nearly full removal of xylan–cellulose linkages, which primes the cellulose for enzymatic attack. The spectral fitting also suggests that the pretreatment causes significant depletion of the inaccessible fibril surface domains with an increase in more thermally stable crystalline resonances (Iβ). WAXS confirmed a decrease in the lattice spacing between (200) crystalline planes with increasing co-solvent pretreatment severity. These results are interpreted as an opening of bound microfibril surfaces previously inaccessible to the co-solvent system, which leaves behind a more thermally stable, crystalline domain that is potentially prone to relaxation and recrystallization. Full conversion of residual GVL-pretreated biomass was achieved after the GVL co-solvent pretreatment at 140 °C using a commercial enzyme cocktail, CTec2, which contains different cellulases and other enzymes. Spectral fitting of enzymatically hydrolyzed samples by a single engineered cellulase, CelR, suggests that the residual cellulose recalcitrance is mainly due to the inability of CelR to digest the Iβ crystalline domain present in pretreated samples. This work helps to provide new information regarding the structure of the cell wall and recalcitrance throughout GVL–water mild acidolysis and CelR enzymatic biomass deconstruction by tracking the evolution of structural domains within the cellulose microfibril. This work further directs recommendations for improving the conversion and sugar yields in future studies. Our findings inform inquiry into larger questions of cellulose recalcitrance through GVL pretreatment and CelR enzymatic hydrolysis and give insight into subsequent required steps for full cellulose conversion with attention to the most recalcitrant cellulose structures.

Tunable Hierarchically Structured Meso-Macroporous Carbon Spheres from a Solvent-Mediated Polymerization-Induced Self-Assembly.

Herein, we report a versatile solvent-mediated polymerization-induced self-assembly (PISA) strategy to directly synthesize highly N-doped hierarchically porous structured carbon spheres with a tunable meso-macroporous configuration. The introduction of intermolecular hydrogen bonds is verified to enhance the interfacial interactions between block copolymers, oil droplets, and polyphenols. Moreover, the dominant hydrogen-bond-driven interactions can be systematically manipulated by selecting different cosolvent systems to generate diverse porous structures from the transformation of micellar and precursor co-assembly. Impressively, hierarchically structured meso-macroporous N-doped carbon spheres present simultaneously tunable sphere sizes and mesopores and macropores, ranging from 1.2 μm, 9/50 and 227 nm to 1.0 μm, 40, and 183 nm and 480, 24, and 95 nm. As a demonstration, dendritic-like N-doped hierarchically meso-macroporous carbon spheres manifest excellent enzyme-like activity, which is attributed to the continuous mass transport from the multiordered porosity. The current study provides a new platform for the synthesis of novel well-defined porous materials.

Water-in-salt electrolytes made saltier by Gemini ionic liquids for highly efficient Li-ion batteries

The water-in-salt electrolytes have promoted aqueous Li-ion batteries to become one of the most promising candidates to overcome safety concerns/issues of traditional Li-ion batteries. A simple increase of Li-salt concentration in electrolytes can successfully expand the electrochemical stability window of aqueous electrolytes beyond 2 V. However, necessary stability improvements require an increase in complexity of the ternary electrolytes. Here, we have explored the effects of novel, Gemini-type ionic liquids (GILs) as a co-solvent systems in aqueous Li[TFSI] mixtures and investigated the transport properties of the resulting electrolytes, as well as their electrochemical performance. The devices containing pyrrolidinium-based GILs show superior cycling stability and promising specific capacity in the cells based on the commonly used electrode materials LTO (Li4Ti5O12) and LMO (LiMn2O4).

Continuous production of cellulose mixed esters via homogeneous reactive twin-screw extrusion catalyzed by ionic liquid

Cellulose mixed esters (CMEs) substituted with two different types of acyl groups are promising polymeric materials with various tunable properties but are arduous to produce. This is because of the insolubility of cellulose in common solvents, and thus, the industrial production of CMEs with desired degrees of substitution (DSs) requires a costly multistep process. To accomplish their facile production, homogeneous reactions have been performed using ionic liquids (ILs) as solvents for cellulose. However, the high viscosity of the cellulose-IL solutions causes insufficient mixing in batch reactors; thereby, favoring low cellulose concentrations with long reaction times (typically hours). Herein, we demonstrate a rapid and scalable production of CMEs by exploiting the excellent shear mixing of a twin-screw extruder as a flow reactor. A co-solvent system comprising an IL, 1-ethyl-3-methylimidazolium acetate, and dimethyl sulfoxide was applied to dissolve cellulose at a high concentration (15 wt.%) via twin-screw extrusion. During continuous extrusion at 80 °C, cellulose reacted with two acyl reagents, isopropenyl acetate (IPAc) and vinyl propionate (VPr) (2.5:0.5, mol/mol), to yield cellulose acetate propionate (CAP) within minutes. The CAP was stably produced during the operation time of 50 min with an average isolated yield of 71%. The DSs of the acetyl and propionyl groups of CAP were 1.77 and 0.50, respectively, corresponding to sufficiently high conversion rates of 70% for IPAc and 100% for VPr.

Complete Low-Temperature Transformation and Dissolution of the Three Main Components in Corn Straw.

The conversion of biomass faces the challenge of mass and heat transfer, as well as the exertion of heterogeneous catalyst, because raw biomass exists usually in solid state. In this work, the simultaneous transformation and dissolution of the three main components (hemicellulose, cellulose, lignin) in corn straw were achieved in ethanol/ valerolactone (GVL)/H2 O (10 : 10 : 40, v/v/v) co-solvent system. With the assistance of AlCl3 ⋅ 6H2 O, the conversion of hemicellulose, lignin and cellulose was >96 % at 170 °C. The conversion of solid biomass into fluid, overcoming the mass transfer restrictions between solid biomass and solid catalysts, provides new raw materials to further upgrading. H2 O could penetrate inside the crystalline cellulose to swell even dissolve it, while ethanol and GVL acted as media to dissolve especially the G unit in lignin. The H+ derived from AlCl3 ⋅ 6H2 O hydrolysis could break the linkages of lignin-hemicellulose and glycosidic bond in saccharides, and aluminum chloride promoted the next degradation of polysaccharides to small molecules. Consequently, as high as 33.2 % yield of levulinic acid and 42.2 % yield of furfural were obtained. The cleavage of β-O-4 and Cβ -Cγ bonds in lignin produced large amounts of lignin-derived dimers and trimers. The total yield of monomeric phenols is up to 8 %.

Self-assembly of unidirectionally polarized piezoelectric peptide nanotubes using environmentally friendly solvents

Diphenylalanine (FF) peptide nanotubes are considered to be particularly promising biomaterials for bio-implantable devices due to their unique characteristics, such as strong piezoelectricity, remarkable physical properties, and chemical stability. However, the 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-water co-solvent system, which is often used for FF nanotube synthesis, is toxic and expensive. These are limitations for the development of eco-friendly and practical biocompatible piezoelectric devices. In this study, we developed an eco-friend and cost-effective approach for aligning piezoelectric FF nanotubes using an ethanol–water solvent system. First, we fabricated horizontally aligned FF nanotubes via a meniscus-driven self-assembly process. The fabricated FF nanotubes using ethanol exhibited unidirectional polarization and strong piezoelectric properties comparable to HFIP solvent based FF nanotubes. In addition, the FF-based piezoelectric nanogenerator generates voltage, current, and power of up to 1.66 V, 19.4 nA, and 19.2 nW, respectively, with a force of 40 N. These FF-based piezoelectric nanogenerators will be applicable as a compatible energy source for future biomedical applications.

Weakly aligned Ti3C2Tx MXene liquid crystals: measuring residual dipolar coupling in multiple co-solvent systems.

Residual Dipolar Coupling (RDC), acquired relying on weakly alignment media, is highly valuable for the structural elucidation of organic molecules. Arising from the striking features of no background signals and low critical concentrations, two-dimensional (2D) liquid crystals (LCs) show the clear advantages of acting as alignment media to measure RDCs. So far, creating multisolvent compatible 2D LC media through a simple and versatile method is still formidably challenging. Herein, we report the rapid creation of aligned media based on the Ti3C2Tx MXene, which self-aligned in multiple co-solvents including CH3OH-H2O, DMSO-H2O, DMF-H2O, and acetone-H2O. We demonstrated the applicability of these aligned media for the RDC measurement of small organic molecules with different polarities and solubilities. Notably, Ti3C2Tx MXene LCs without chemical modification enabled RDC measurements on aromatic molecules. The straightforward preparation of Ti3C2Tx media and its compatibility with multiple solvents will push RDC measurement as a routine methodology for structural elucidation. It may also facilitate the investigation of solvation effects on conformational dynamics.

Scalable Non-Halogenated Co-solvent System for Large-Area, Four-Layer Slot-Die-Coated Organic Photovoltaics

Sustainable processing solvents, photoactive materials, and scalable manufacturing will play a key role in commercializing printed organic photovoltaics (OPVs). The record-breaking pioneering OPV reports have done an outstanding job in accelerating the discovery of champion photoactive materials and device engineering practices; however, these works predominantly involve health-hazardous halogenated processing solvents/additives and non-scalable thin-film coating methods. Herein, large-area slot-die-manufactured OPV cells from eco-friendly halogen-free solvents and synthetically scalable materials are showcased. All the four layers; electron transport layer (SnO2), cathode interlayer (PDIN-H), bulk-heterojunction (BHJ, PTQ-10:BTP-4F-12), and hole transport layer [poly(3,4-ethylenedioxythiophene):polystyrene sulfonate) (PEDOT:PSS] are slot-die-coated in air. A non-halogenated co-solvent mixture of toluene and 2-methyl tetrahydrofuran is presented as an optimal processing solvent to realize the high-quality thin films of PTQ10:BTP-4F-12. The unencapsulated champion solar cells characterized in ambient conditions (RH = 30%, T = 22 °C) exhibit power conversion efficiencies (PCEs) of 12.1 and 17.8% under 1 Sun (100 mW/cm2) and indoor light-emitting diode lighting (580 μW/cm2) conditions, respectively. Additionally, PEDOT:PSS is successfully slot-die-coated atop BHJ by mitigating wettability challenges with the aid of surface treatment. The all four-layer slot-die-coated OPVs exhibit a PCE of 9.55%.

In-situ lignin sulfonation for enhancing enzymatic hydrolysis of poplar using mild organic solvent pretreatment

Biomass pretreatment is an essential strategy to overcome biomass recalcitrance and promote lignocellulosic bioconversion. Here, a reusable organic solvent system (formic acid-methanesulfonic acid) was explored to pretreat poplar under a mild temperature (below 100 °C). The results showed that the co-solvent system could extract basically complete hemicelluloses and part of lignin with original cellulose retained in the pretreated substrates. Meanwhile, sulfonic acid groups were introduced into lignin structure remained in the substrates. The glucose conversion yield of the substrates with a higher concentration of sulfonic acid groups (13.2 mmol/kg) reached 45.9 % by reducing the hydrophobic interaction between lignin and cellulase, showing 89.3 % improvement compared with that of the substrates treated with single formic acid. This progressive study aimed to develop a new strategy to realize sulfonation and promote enzymatic hydrolysis of substrates by using mild organic solvent pretreatment.

Thermodynamic study of solubility of B6 hydrochloride in water + co-solvent systems with UNIQUAC model at different temperatures

In this study, due to the importance of the solubility of this vitamin in solvents, based on the UNIQUAC activity coefficient equation, its solubility in the presence of water, acetonitrile, n-propanol and isopropanol has been studied. To investigate the interaction behavior of components in the system, the desired thermodynamic equations were optimized based on experimental results with a combined Genetic + PSO algorithm. Based on the objective function, the value of the theoretical and experimental model was acceptable. Therefore, the optimized model can be significant for formulating and investigating solubility of B6 hydrochloride based on the design of a computer program.

Liposomal system based on lyophilization of a monophase solution for stabilization of bioactives from red onion skin

Encapsulation of obtained polyphenolic extract from red onion skin was performed in phosphatidylcholine-based liposomes based on freeze-drying of the single-phase solution using tert-butyl alcohol-water cosolvent system. The highest amounts of anthocyanins and polyphenols extraction were obtained at 60% ethanolic media without acetic acid. Two batches of nanoliposomes, loaded with obtained bioactives, yielded the nanoliposome particle size of 159.4–177.3 nm, PDI of 0.65–0.7, and zeta potential of −38 to −28.6 mV. The encapsulation efficiency of the prepared nanoliposomes was reported to be higher than 68.42%. The samples exhibited higher stability at 4 °C than 25 °C during 21 days of storage. The spherical and uniform shape of the nanoliposomes and the interactions between the anthocyanins and the nanoliposomes were confirmed by TEM and FTIR tests, respectively. As for the anthocyanin release in the two hydrophilic and lipophilic food simulants, the results indicated the higher release of the anthocyanins in the hydrophilic solution. In general, the liposomal system used for encapsulating poly phenol rich extract from red onion skin can be applied for control release in food products.

Crystallization and phase selection of zeolitic imidazolate frameworks in aqueous cosolvent systems: The role and impacts of organic solvents

Zeolite Imidazolate Frameworks (ZIFs) can be used in a wide range of applications, such as water treatment, molecular sieving, gas adsorption, drug delivery, and catalysis. However, their fabrications in primarily aqueous environments have succumbed to large chemical consumption and become very challenging in sustainable manufacturing. However, the water-organic cosolvent system enables ZIF fabrications at lower chemical consumption (e.g., lower ligand-to-metal ratios and contents in the synthesis system) and resulting materials with interesting nanostructures and surface properties. Herein, aqueous-based fabrications were successfully employed with various cosolvents, including alcohols, ketones, and amides. Their impacts on ZIF (ZIF-L/ZIF-8 as examples) nucleation, crystallization, phase transformation, and morphological evolution were systematically studied. Each solvent environment enhanced the coordination of the metal sites to different degrees. Specifically, ZIF-8 formation was favoured in cosolvent concentrations of 50 v/v%, 25 v/v%, 5 v/v%, 10 v/v%, 10 v/v%, and 25 v/v% for methanol, ethanol, n-propanol, isopropanol, acetone and DMF, respectively. Moreover, the preferential formation towards ZIF-8 in each cosolvent environment resulted in similar BET surface areas, in the range of 1350–1376 m2 g−1, highlighting good reproducibility of cosolvent-assisted syntheses. In this work, a formation mechanism was drawn for various solvents in terms of solvent properties, metal site interactions, and deprotonation capabilities. This newly proposed mechanism of ZIF growth provides vital information regarding the solvents' roles in aqueous-based fabrications and their impacts on crystallinity, structure purity, and crystal morphology as well as new insights for researchers working on the synthesis and structure control/modifications of ZIFs & their composite materials.

Two carriages for efficient furfural production from biomass: Rational design of porous biochar catalyst and clever utilization of butyrolactone-water medium

In the conversion of lignocellulosic biomass to furfural, a low yield is often obtained due to the natural degradation-resistant structure of the biomass and the high reactivity of the furfural molecule. However, in this study, the efficient conversion of biomass to furfural (90.5 % furfural yield) was achieved by working in the coordination of both carbon-based solid acid catalyst and water-butyrolactone co-solvent system using bagasse pith biomass as feedstock. The solid acid catalyst prepared by loaded sulfonic acid groups and Fe3+ on biochar showed a high specific surface area and well-developed pore channels, which can facilitate the breakdown of the solid structure of bagasse pith and the adequate hydrolysis. Meanwhile, by adjusting the volume ratio of the co-solvent system, the water in the system can not only foster the hemicellulose hydrolysis in bagasse pith but also facilitate the dehydration of xylose to form furfural. Furthermore, it enables the butyrolactone in the system to form a protective layer around the furfural molecule in time to avoid the degradation condensation reaction of the furfural molecule in the acidic system. Eventually, the 90.5 % furfural yields were obtained at water-butyrolactone volume ratio, reaction temperature, and reaction time were 1:29, 190, and 3 h, respectively.

Thermodynamic Analysis of the Solubility of Isoniazid in (PEG 200 + Water) Cosolvent Mixtures from 278.15 K to 318.15 K.

The solubility of drugs in cosolvent systems of pharmaceutical interest is of great importance for understanding and optimizing a large number of processes. Here, we report the solubility of isoniazid in nine (PEG 200 + water) cosolvent mixtures at nine temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, and 318.15 K) determined by UV–vis spectrophotometry. From the solubility data, the thermodynamic solution, mixing, and transfer functions were calculated in addition to performing the enthalpy–entropy compensation analysis. The solubility of isoniazid depends on the concentration of PEG 200 (positive cosolvent effect) and temperature (endothermic process) reaching its maximum solubility in pure PEG 200 at 318.15 K and the lowest solubility in pure water at 278.15 K. The solution process is favored by the solution entropy and according to the enthalpy–entropy compensation analysis it is driven by entropy in mixtures rich in water and by enthalpy in mixtures rich in PEG 200.