On the microstructures of ethyl acetate/monoolein/water

A phase diagram, describing the behavior of the polar lipid monoolein (MO), water, and ethyl acetate (EtAc), is here presented as well as results from small angle X-ray scattering. MO is found to have a solubility of 60 wt.% in EtAc at 20 °C. No macroscopic aggregation of MO can, initially, be detected in the binary MO/EtAc solution even though MO forms solid crystals in concentrated samples when times goes by. In case of the ternary system small amounts of water, mainly bound to the lipid head groups, can be incorporated in the liquid EtAc/MO phase as water has a limited solubility in EtAc. For EtAc/water mass ratios below 2/3 EtAc is present into the reversed bicontinuous cubic and lamellar phases present in the binary MO/water system. To conclude, EtAc is mainly partitioned to the lipid membranes, with minor effects on spontaneous curvature. Hence, simple EtAc-addition has an effect similar to dehydration. For EtAc/water ratios above 2/3 the liquid crystalline phases dissolve. The phase behavior is here discussed in view of related phase behaviors for water-miscible solvent/MO/water systems. For instance, an interpretation of the swelling behavior of the sponge phase (L₃), present in the water-miscible solvent(s)/MO/water systems, shows that solvents partitioned to the polar domains strongly increases the spontaneous curvature of the MO-films. The reason is probably weaker hydrophobic interactions in interfacial regions. As expected, in case of water-miscible solvents, the ternary phase behaviors can be understood by consider water and water-miscible solvent as one “mixed solvent”.     

Equation of state modeling of the phase equilibria of ionic liquid mixtures at low and high pressure

Accurate design of processes based on ionic liquids (ILs) requires knowledge of the phase behavior of the systems involved. In this work, the truncated perturbed chain polar statistical associating fluid theory (tPC-PSAFT) is used to correlate the phase behavior of binary and ternary IL mixtures. Both non-polar and polar solvents are examined, while methyl imidazolium ILs are used in all cases. tPC-PSAFT accounts explicitly for weak dispersion interactions, highly directive polar interactions between permanent dipolar and quadrupolar molecules and association between hydrogen bonding molecules. For mixtures of non-polar solvents, tPC-PSAFT predicts accurately the binary mixture data. For the case of polar solvents, a binary interaction parameter is fitted to the experimental data and the agreement between experiment and correlation is very good in all cases.     

Segregation of lipid and polymer in emulsion droplets captured by confocal laser scanning microscopy

The phase behaviors of the subsystems of the ethyl acetate (EtAc)/monoolein/polyethylene glycol-poly(D,L-lactide-co-glycolide) (PLG)/water system have been determined. EtAc simultaneously solves MO and PLG in a liquid phase, denoted L. Lipid/polymer composite particles have here been formed by emulsification of such an L phase into aqueous solutions. Characterization, by means of confocal laser scanning microscopy, revealed that distinctive lipid domains appear inside the particles. In aqueous solutions, these lipid domains swell and finally leave the concentrated polymer matrix. The system exhibits a suitable phase behavior in order to form lipid/polymer composite particles. These composite particles may be interesting for drug delivery applications.     

Solubility prediction of anthracene in mixed solvents using a minimum number of experimental data

Numerical methods to predict the solubility of anthracene in mixed solvents have been proposed. A minimum number of 3 solubility data points in sub-binary solvents has been employed to calculate the solvent-solute interaction terms of a well established colsolvency model, i.e. the combined nearly ideal binary solvent/Redlich-Kister model. The calculated interaction terms were used to predict the solubility in binary and ternary solvent systems. The predicted solubilities have been compared with experimental solubility data and the absolute percentage mean deviation (APMD) has been computed as a criterion of prediction capability. The overall APMD for 25 anthracene data sets in binary solvents is 0.40%. In order to provide a predictive method, which is based fully on theoretical calculations, the quantitative relationships between sub-binary interaction terms and physicochemical properties of the solvents have been presented. The overall APMD value for 41 binary data sets is 9.19%. The estimated binary interaction terms using a minimum number of data points and the quantitative relationships have then been used to predict anthracene solubility data in 30 ternary solvent systems. The produced APMD values are 3.72 and 15.79%, respectively. To provide an accurate correlation for solubility in ternary solvent systems, an extension to the combined nearly ideal multicomponenet solvent/Redlich-Kister (CNIMS/R-K) model was proposed and the corresponding overall AMPD is 0.38%.     

Models to predict solubility in ternary solvents based on sub-binary experimental data

The capability of the extended forms, of two well established cosolvency models, i.e. the combined nearly ideal binary solvent/Redlich-Kister equation and the modified Wilson model, used to predict the solute solubility in non-aqueous ternary solvent mixtures is presented. These predictions are based on the measured solubilities of anthracene in binary solvent mixtures. As a result the values of average percent deviations were less than 2% for the anthracene solubility in ternary mixtures. This work was also extended to other cosolvency models, ie. the extended Hildebrand solubility approach and the mixture response surface method, which are also commonly used for correlating solubility data in ternary solvents. The accuracy of the models is compared with each other and also with a published solubility model for ternary mixtures. The results illustrate that all models produced comparable accuracy.     

Phase diagram of the ternary system NMMO/water/cellulose

The phase diagram of the system N-methylmorpholine-N-oxide(NMMO)/H₂O/cellulose has been measured at 80 °C by establishing a solubility map (observation of the mixtures under the microscope), by the analysis of coexisting phases and determining the critical point. These experiments manifest a continuous reduction of the two phase area existing for the subsystem H₂O/cellulose upon the addition of NMMO, where a weight fraction of NMMO in the mixed solvent exceeding 75 wt% is required for Solucell 400 to reach the critical composition. The critical cellulose concentration is only 0.34 wt%, i.e., more than an order of magnitude lower than for the solutions of typical vinyl polymers in mixed solvents. All experimental observations can be well modeled on the basis of composition dependent binary interaction parameters by means of recently established mixing rules. For the subsystems H₂O/cellulose and NMMO/water the corresponding data are known from independent earlier measurements. The adjustment of two parameters to the ternary phase diagram was required to obtain this information for NMMO/cellulose, the third binary subsystem.     

Solubility prediction of paracetamol in binary and ternary solvent mixtures using Jouyban-Acree model

The Jouyban-Acree model has been used to predict the solubility of paracetamol in water-ethanol-propylene glycol binary and ternary mixtures based on model constants computed using a minimum number of solubility data of the solute in water-ethanol, water-propylene glycol and ethanol-propylene glycol binary mixtures. Three data points from each binary solvent system and solubilities in neat solvents were used to calculate the binary interaction parameters of the model. Then the solubility at other binary solvent compositions as well as in a number of ternary solvents were predicted, and the mean percentage deviation (+/-S.D.) of predicted values from experimental solubilities was 7.4(+/-6.1)%.     

A New Quaternary Mobile Phase System for Optimization of TLC Separations of Alkaloids Using Mixture Designs and Response Surface Modelling

Abstract

A new combination of four organic solvents is proposed for the optimization of TLC separations of basic drugs and alkaloids. The solvents are diethylamine (DEA), methanol (MeOH), chloroform (CHCl₃) and ethylacetate (EtAc). They were selected from a collection of ten solvents used in Normal Phase TLC mobile phases recommended for the separation of alkaloids and basic drugs in the literature. The selection was based on the classification of solvents according to selectivity and solubility parameters. Excluded were apolar and weak solvents that show no selective (polar) properties and are used only for the adjustment of the solvent strength. Polar solvents from different selectivity groups were selected to combine as many as possible selective effects in one solvent system. The final choice was made considering the displacement theory for Liquid Solid Chromatography.     

Ternary complexes in agarose gels prepared from binary solvents

The thermoreversible gelation of agarose has been investigated in four different aqueous binary solvents: Water/dimethyl sulfoxide, water/N,N-dimethylformamide, water/N-methylformamide, and water/formamide. The phase diagrams have been subsequently established as a function of agarose concentration and solvent composition. These diagrams suggest the formation of ternary complexes agarose/water/cosolvent.     

Solubility of Ketoconazole in Binary and Ternary Solvents of Polyethylene Glycols 200, 400 or 600 with Ethanol and Water at 298.2 K. Data Report and Analysis

The solubilities of ketoconazole in binary and ternary mixtures of water, ethanol and polyethylene glycols 200, 400 or 600 (185 data points) were determined at 298.2 K. Williams–Amidon and Jouyban–Acree cosolvency models were used to model the data, with overall mean relative deviations (OMRDs) for the solubility data in binary and ternary solvents of 17.5 and 23.5%, respectively. For predicting the solubility data of ketoconazole the trained versions of the models were used and the OMRD values were 47.7 and 33.0%, respectively.     

Binary Interaction Parameters,Ternary Systems: Realistic Modeling of Liquid/Liquid Phase Separation

The phase behavior of ternary systems (either a polymer solution in a mixed solvent or a polymer blend in a single solvent) was modeled theoretically. The modeling considers two specific features of polymers explicitly: chain connectivity and the ability to respond to changes in the molecular environment by conformational reorientation. Previously, this approach has been applied to polymer solutions in single solvents. Here it is generalized and the number of parameters is reduced to two per binary system. The calculation of the Gibbs energies of the ternary mixtures accounts for the composition dependencies of the binary interaction parameters. The following phenomena are reproduced realistically for polymer solutions in a mixed solvent and for solutions of two polymers in a common solvent: simplicity, co‐solvency, and co‐non‐solvency. The results nourish the hope that the new approach is capable of modeling phase diagrams for ternary systems by means of binary interaction parameters only.

     

How small polar molecules protect membrane systems against osmotic stress: the urea-water-phospholipid system

We investigate how a small polar molecule, urea, can act to protect a phospholipid bilayer system against osmotic stress. Osmotic stress can be caused by a dry environment, by freezing, or by exposure to aqueous systems with high osmotic pressure due to solutes like in saline water. A large number of organisms regularly experience osmotic stress, and it is a common response to produce small polar molecules intracellularly. We have selected a ternary system of urea-water-dimyristoyl phosphatidylcholine (DMPC) as a model to investigate the molecular mechanism behind this protective effect, in this case, of urea, and we put special emphasis on the applications of urea in skin care products. Using differential scanning calorimetry, X-ray diffraction, and sorption microbalance measurements, we studied the phase behavior of lipid systems exposed to an excess of solvent of varying compositions, as well as lipid systems exposed to water at reduced relative humidities. From this, we have arrived at a rather detailed thermodynamic characterization. The basic findings are as follows: (i) In excess solvent, the thermally induced lipid phase transitions are only marginally dependent on the urea content, with the exception being that the P(beta) phase is not observed in the presence of urea. (ii) For lipid systems with limited access to solvent, the phase behavior is basically determined by the amount (volume) of solvent irrespective of the urea content. (iii) The presence of urea has the effect of retaining the liquid crystalline phase at relative humidities down to 64% (at 27 degrees C), whereas, in the absence of urea, the transition to the gel phase occurs already at a relative humidity of 94%. This demonstrates the protective effect of urea against osmotic stress. (iv) In skin care products, urea is referred to as a moisturizer, which we find slightly misleading as it replaces the water while keeping the physical properties unaltered. (v) In other systems, urea is known to weaken the hydrophobic interactions, while for the lipid system we find few signs of this loosening of the strong segregation into polar and apolar regions on addition of urea.     

Solubility and Thermodynamic Properties of A Hexanediamine Derivative in Pure Organic Solvents and Nonaqueous Solvent Mixtures

The solubility of N,N′-Bis(2,2,6,6-tetramethyl-4-piperidinyl)-1,6-hexanediamine in seven pure solvents (acetonitrile, acetone, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate and isobutyl acetate) and two binary solvent mixtures (acetone?+?acetonitrile and methyl acetate?+?acetonitrile) were measured from 273.15 to 303.15 K at atmospheric pressure by a dynamic method. The solubility data in these pure solvents were correlated by the modified Apelblat model, the Wilson model and the NRTL model, and that in the binary solvents mixture were fitted to the CNIBS/R–K model and the NRTL model. Furthermore, the mixing thermodynamic properties in pure and binary solvent systems were calculated and are discussed, based on the NRTL model. Finally, the applicability of the model of Zhang et al. (Ind Eng Chem Res 51:6933–6938, 2012) in correlating solubility data versus dielectric constant was extended from organic solvent–water mixtures to pure organic solvents and nonaqueous organic solvent mixtures. It was found that the dissolution behavior of a compound in the binary solvent mixtures can be predicted to some extent from those in pure solvents.     

Effectivity of solvents-A new approach in non-aqueous acid-base titrimetry

A new approach for selection of a suitable solvent system as a medium for non-aqueous acid—base titration is proposed. The essence of the approach is the development of a new criterion called “effectivity”. The latter is based on consequences of the Brønsted and Izmailov acid—base theories and represents a quantitative measure for improving or worsening the titration conditions of acids and bases in non-aqueous solvents as compared with water. The “effectivity” E is given by the relation E = ΔpK_s - ΔpK_s where ΔpK_s is the difference between the logarithmic values of the autoprotolysis constants of water and the solvent in question, and ΔpK is the so-called medium effect. The latter is a constant value which shows that acids and bases with the same charge alter their strength to the same extent when transferred from water into a non-aqueous solvent. The medium effect is calculated by statistical treatment of a great number of acid—base constants determined experimentally both in water and the non-aqueous solvent in question. The effectivity of the solvents most often used in non-aqueous acid—base titrimetry, determined by this approach, shows that in many cases these solvents offer significant advantages over water, but drawbacks are also observed. Some limitations of the approach are discussed. Special attention is paid to dimethylsulphoxide and its mixtures with water, which prove to be highly effective media for the acid—base titration of many substances.     

Mechanism and prediction of retention of oligomers in normal-phase and reversed-phase HPLC

Summary The simultaneous dependence of the retention in oligomeric series on the number of repeat structural units and on the mobile phase composition may be described by very similar equations for reversed-phase and for normal-phase systems.In reversed-phase systems, the separation selectivity of the individual oligomers is determined mainly by the size and by the polarity of the repeat structural unit, but the influence of a bulky and polar structural residue may also become important so that even reversed order of elution may be observed for oligomeric series with the same oligomeric units but significantly different end groups. For example, oligoethylene glycols are eluted in the order of increasing size of the oligomers, whereas ethoxylated nonylphenols are eluted in the order of decreasing size.In normal-phase systems, the separation selectivity in oligomeric series depends on the adsorption energy and on the adsorbed area of the oligomeric unit. If the oligomeric unit is small, the concentration of the polar solvent in the binary organic mobile phase has only a minor effect on retention and selectivity, which may be controlled by taking account of the nature of the adsorbent and of the polar solvent or by varying the proportion of two polar solvents in a ternary mobile phase.     

Determination and Correlation of the Solubility of Acetylpyrazine in Pure Solvents and Binary Solvent Mixtures

The solubilities of acetylpyrazine in seven pure solvents and one binary solvent mixture were determined by a dynamic analytic method at temperatures ranging from 268.15 to 308.15 K under atmospheric pressure. For pure solvents, the solubility of acetylpyrazine increases with increasing temperature and solvent polarity. For the binary solvent mixture of ethyl acetate and isopropanol, the solubility increases with increasing temperature and mole fraction of ethyl acetate. The solubility data were correlated with some thermodynamic models, including the modified Apelblat model, λh model, CNIBS/R-K model, and NRTL model. In addition, the relationship between solubility and solvent polarity was investigated by using the Arrhenius equation. All the models or equations gave satisfactory correlation results. The results showed that the solubility of acetylpyrazine generally rises with the increase of solvent polarity at the same temperature. Moreover, the dissolution thermodynamic properties of acetylpyrazine in different solvents were calculated and are discussed based on the NRTL model.     

Solubility Data of Diazepam in Binary and Ternary Mixtures of PEGs 200 and 400 with N-Methyl Pyrrolidone and Water at 298.2 K: Experimental Data and Modeling

Experimental solubilities of diazepam in binary and ternary solvents of polyethylene glycols 200 and 400 with N-methyl pyrrolidone and water at T = 298.2 K are reported. The Jouyban–Acree model was used to fit solubility data of diazepam in the binary and ternary solvent mixtures (106 data points) in which the overall mean relative deviations (OMRD %) is 13.1 % and the prediction OMRD % is 31.7 %. The combined version of the Jouyban–Acree model with Hansen solubility parameters was used for fitting and predicting the solubility data and the OMRDs % are 10.0 and 20.8 %, respectively. Also, the previously proposed trained versions of the Jouyban–Acree model were used for predicting the reported data in this work and all results are listed in the tables. The density of the solute-free solvent mixtures were measured and employed to calculate the constants of the Jouyban–Acree model and then the densities of the saturated solutions were predicted.     

Retention prediction in ternary solvent reversed-phase liquid chromatography systems based on the variation of retention with binary mobile phase composition

An extension of the treatment adopted in a recent paper [P. Nikitas, A. Pappa-Louisi, P. Agrafiotou, J. Chromatogr. A 946 (2002) 33] was used to derive expressions describing the variation of solute retention k with composition in ternary reversed phase liquid chromatography, RP-LC, solvent systems. The equation of the partition model obtained in this way for a ternary mobile phase was identical to that previously derived using the solubility parameter concept. This equation as well as two new expressions of In k versus organic modifiers content were tested in a variety of ternary solvent systems in order to examine the possibility of predicting retention behavior of solutes under ternary solvent mixture elution conditions from known retention characteristics in binary mobile phases. It was demonstrated the superiority of both new equations derived in this paper to that previously proposed and applied to date in ternary solvent mixtures.     

Polymer conformation in mixed aqueous-polar organic solvents

The conformation of the common polysaccharide dextran has been investigated in mixed solvents at two different temperatures using viscosity measurements. In particular we considered binary mixtures of water with the polar organic solvents glycerol, formamide, dimethylsulfoxide, or ethanol. The intrinsic viscosity of dextran T500 in the different systems has been determined, and the solvent effects, as manifested in variations of the dextran intrinsic viscosity and coil radius, have been correlated to the surface tension and the fractional solubility parameters of the solvent mixture. The coil dimension changes observed in the different solvent mixtures are consistent with expectations from water-cosolvent-dextran interactions, especially as they pertain to hydrogen bonding.     

Evaluation of common organic solvents for gas chromatographic analysis and stability of multiclass pesticide residues

In this study, we evaluated the suitability of six common organic solvents for gas chromatographic (GC) analysis of pesticides. Three of these, acetone, acetonitrile (MeCN) and ethyl acetate (EtAc), represent extraction solvents commonly used in multiresidue methods for determination of pesticides in produce. The other three, isooctane, hexane and toluene, often serve as exchange solvents before a GC analysis. An ideal solvent for GC analysis of multiclass pesticide residues should be compatible with: the analytes, sample preparation, and GC analysis. This study addresses each aspect with emphasis placed on stability of selected pesticides in the given solvents. In this respect, the exchange solvents proved to be superior to the more polar extraction solvents. Degradation of N-trihalomethylthio fungicides (e.g., captan, folpet, dichlofluanid) in MeCN was observed only in certain lots of the tested MeCN, but even if it occurred, the stability of these analytes as well as that of dicofol and chlorothalonil was dramatically improved by the addition of 0.1% (v/v) acetic acid. Dicofol and chlorothalonil were also unstable in acetone, and pesticides with a thioether group (e.g., fenthion, disulfoton) degraded in the tested EtAc. Formation of isomers of certain pyrethroids (deltamethrin, lambda-cyhalothrin) was recorded in the chromatograms from MeCN and acetone solutions, but this effect more likely occurred during the GC injection than in solution. For several reasons, MeCN was found to be the most suitable solvent for extraction of a wide polarity range of pesticide residues from produce. After acidification, the stability of problematic pesticides in MeCN is acceptable, and MeCN can also serve as a medium for GC injection; therefore solvent exchange is generally not required before GC analysis. If sensitivity is an issue in splitless injection, then toluene was demonstrated to be the best exchange solvent due to its miscibility with MeCN and stronger responses of relatively more polar pesticides (e.g., acephate, methamidophos) as compared to hexane and isooctane.