Mixed Solvent Solutions Research Articles

Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles

Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2–8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0–9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.

A New Method of Producing Monoclinic Paracetamol Suitable for Direct Compression

To develop a technique of obtaining monoclinic polymorph of paracetamol suitable for direct compression without excipients. Preparation of spongy monoclinic paracetamol was based on quench-cooling of paracetamol solutions in water-acetone mixtures sprayed into a vessel with liquid nitrogen followed by removal of solvents by freeze-drying. X-ray powder diffraction was used to study annealing of quench-cooled solutions in "paracetamol-acetone-water" and "acetone-water" systems and to find optimum conditions for obtaining fine particles of pure monoclinic paracetamol. Samples were characterized by electron microscopy; compression properties were measured. The preparation technique gave fine monoclinic paracetamol powder containing agglomerates (30-200 μm) composed of flat particles (linear sizes 1-10 μm, the thickness 60-150 nm). The spongy sample was suitable for direct compression without excipients, stable on storage, and mechanically robust. Mechanically stable tablets pressed from the spongy sample were better soluble in water than commercially available tablets of paracetamol with excipients. The proposed method gave spongy monoclinic paracetamol samples with improved properties. For inexpensive paracetamol, the method may not yield economic advantage. However, the same method based on freeze-drying solutions in mixed aqueous-organic solvents can be used to prepare new improved forms of other molecular solids for pharmaceutical applications.

Controllable Nanocarving of Anatase TiO2 Single Crystals with Reactive {001} Facets

Owing to its wide applications in photocatalysis, photo/ electrochromics, solar cells, sensors, and smart surface coatings, anatase titanium dioxide (TiO2) has attracted intensive research interests during the past decades. Most available and stable anatase TiO2 single crystals have truncated octahedral-bipyramid shapes, in which the majority of the surface area is normally surrounded by thermodynamically stable {101} facets, rather than the more reactive {001} facets. For a long period, tailored synthesis of {001}-faceted anatase TiO2 single crystals has been a great challenge. Recently, we made a breakthrough in the hydrothermal synthesis of anatase TiO2 single crystals with a large percentage (35–47%) of highly reactive {001} facets by using hydrofluoric acid (HF) as a specific morphology-controlling agent. Later, with the assistant of isopropanol (iPrOH)—a synergistic capping agent together with HF, anatase TiO2 single crystals with a higher ratio of {001} facets were prepared through a water–isopropanol solvothermal synthetic route. During these processes, HF was reported to act as a capping agent by reversing the relative stability of {001} and {101} facets and therefore promoting the growth of {001}faceted surfaces of anatase TiO2. By using similar strategies, a series of studies by research groups worldwide have demonstrated the syntheses and applications of anatase TiO2 with exposed reactive {001} facets. Unfortunately, few researchers have explored the etching effect of HF, which was traditionally considered a strong etching agent for metal oxides. Thus studying the chemical stability of {001}-faceted anatase TiO2 in the presence of HF is quite important and can help to understand the real function of HF during these important chemical processes. Herein, the dual role of HF—as capping agent and etching agent—is revealed through the controllable nanocarving of {001}-faceted anatase TiO2 single crystals. This process was realized through thermal treatment of anatase TiO2 single crystals with 35% of {001} facets by using HF-containing solutions or just by one-step solvothermal reactions of aqueous titanium tetrafluoride (TiF4) solutions in mixed solvents containing HF. In addition, a feasible mechanism is proposed to clarify the etching process involving HF and the growth process of the anatase TiO2 products with diverse morphologies. Figure 1a presents a typical SEM image of anatase TiO2 single crystals with 35% of reactive {001} facets, which was synthesized according to the method described in our earlier

Dielectric Function and Electronic Excitations of Functionalized DNA Thin Films

We measure the dielectric functions of organic-soluble, functionalized DNAs bearing functional moieties in the near-infrared, visible, and ultra-violet spectra by using spectroscopic ellipsometry. Natural double-stranded DNA is dissolved in water and reacted with carbazole-based trimethyl ammonium bromide, cetyltrimethylammonium bromide, and chalcone-terminated trimethyl ammonium bromide. The functional DNA products are all precipitated and filtered for washing and drying. We successfully prepare functionalized DNAs that are insoluble in water but soluble in organic solvents. The thin films are fabricated by using the spin coating technique after preparing solutions in either homogeneous or mixed organic solvents. We measure the ultraviolet–visible absorbance spectra of the films. The absorbance spectra show that the optical energy gaps of the functionalized DNAs change little even though the DNAs are connected to the complex molecules by electrostatic interaction. From the measured ellipsometric angles, we estimate the dielectric functions by using parametric optical constant model and layer model analysis. Depending on the nature of the attached complex molecules, the dielectric functions change, new optical structures develop below and above band gaps arising from the side molecules, and the optical energy gaps of the DNAs are altered slightly by weak coupling to the tethered complex molecules.

ДослідженнЯ адсорбціЇ компонентіВ З бінарноЇ сумІшІ органічниХ розчинникіВ

Results of superficial tension determinaition of solutions of mixed solvents on the basis of perchloroethylene and 2-propanol are resulted, characteristics of absorption monolayer of their molecules are calculated. Regularities of solvents adsorption by textile materials are investigated.

Molecularly imprinted polymer (MIP) based piezoelectric microgravimetry chemosensor for selective determination of adenine

An adenine-templated molecularly imprinted polymer (MIP) film, deposited on a poly(bithiophene) barrier film, served as the recognition element of a piezomicrogravimetric (acoustic) chemosensor. A 10 MHz AT-cut shear-thickness-mode bulk-acoustic-wave quartz crystal resonator with Pt film electrodes was used as the signal transducer. Adenine electrooxidation was prevented by the barrier film. The MIP film was deposited by electrochemical co-polymerization of two functional monomers of bis(bithiophene) derivatives, bearing either the 18-crown-6 or dioxaborinane substituent, in the presence of the adenine template. A strong base solution was then used to extract the template. Completeness of the template removal was substantiated by the UV–vis, XPS, DPV, and EIS measurements. The chemosensor performance was evaluated with the piezoelectric microgravimetry detection at QCM under FIA conditions using a carrier acetonitrile–water (1:1, v: v) mixed solvent solution. The linear dynamic concentration range extended from at least 0.1 to 1 mM for the 35 μL/min flow rate, and 100 μL volume of the injected adenine solution. The chemosensor selectivity allowed for discrimination of the adenine analyte from structurally and functionally related interferants, such as 2-aminopurine, guanine, and ascorbic acid. The determined from the FIA kinetic studies stability constant of the MIP–adenine complex, (18 ± 2.4) × 10 4 M −1, was much higher than that of the MIP–(2-aminopurine), (650 ± 90) M −1, MIP–guanine, (122 ± 11) M −1, and MIP–(ascorbic acid), (92 ± 10) M −1, complexes. The concentration limit of detection was as low as 5 nM adenine for the 35 μL/min flow rate, and 1 mL volume of the injected sample solution.

Mechanism of Reductive C60 Electropolymerization in the Presence of Dioxygen and Application of the Resulting Fullerene Polymer for Preparation of a Conducting Composite with Single-Wall Carbon Nanotubes

The superoxide anion radical, O2•−, induced C60 electropolymerization mechanism was refined by simultaneous cyclic voltammetric (CV) and vis-NIR spectroelectrochemical as well as mass spectrometric (MALDI-TOF) characterization of the one- and two-electron reduction products of C60 in the presence of O2 in a mixed organic solvent solution. The C60 polymer (C60-O) film was also investigated by Raman spectroscopy and imaged by atomic force microscopy (AFM) both at the early and advanced polymerization stage. While the spectroelectrochemical behavior of the C60/C60•− couple in the presence of O2 was similar to that in its absence, at more negative potentials corresponding to C602− and O2•− formation C602− participated in a chemical follow-up reaction resulting in a product lacking any diagnostic absorption band in the vis-NIR range. Although the main peak in the MS spectrum of the one-electron reduction product was that of C60 at m/z of 720, several additional peaks in the m/z range of 739−760 appeared, indic...

Formation and Characterization of P(VDF-TeFE) Films Using Sol-Gel Methods for Application to Micro-Generators

In order to apply the P(VDF-TeFE) piezoelectric polymer to the micro-generator based on MEMS technology, we have established a process condition of the film formation. A solvent which is used to cast P(VDF-TeFE) solution is important factor for film formation, and MEK solvent has some problems such as low adhesion for low concentration and drying on a coating process for high concentration. Some problems are suppressed by adding a DMA solvent. However, a DMA solvent affected a molecular structure of the film. A thermal treatment is also an important factor since film stretching cannot be allowed in a spin-coating process. In order to compare the single-solvent solution with the mixed-solvent solution, we have carried out qualitative analysis of the film in formation processes.

On the Viscoelastic and Dielectric Behavior of Some Organic Compounds and Their Binary Mixtures

The dependence of dielectric relaxation time on the viscosity of the medium is being extensively used to draw certain quantitative conclusions regarding molecular motion and inter-molecular forces in liquids, liquid mixtures, dilute solutions, and multi-component polar solutes in dilute solution. In the absence of proper empirical or theoretical equations for the variation of dielectric relaxation time with viscosity, only the experimental investigations on different systems can give an insight. In the present study, the results of dielectric measurements carried out on pure samples of bromohexane, bromooctane and bromodecane in dilute solutions in different mixed solvents (benzene + paraffin) and on binary mixtures (1 : 1) of (bromohexane + bromodecane); (bromodecane + propyl alcohol) and (propyl alcohol + methyl alcohol) are reported. For comparison, the results of bromodecane + propyl alcohol and propyl alcohol + methyl alcohol are chosen as they form examples of mixture of non-associative + associative and associative + associative liquids, respectively. Different parameters determined using these dielectric measurements are also presented using different models. These studies indicate that the dielectric behavior at microwave frequencies favor the concept of dynamic viscosity and a single viscoelastic relaxation time for the systems under study.

Method for predicting solubilities of solids in mixed solvents

AbstractA method is presented for predicting solubilities of solid solutes in mixed solvents, based on excess Henry's law constants. The basis is statistical mechanical fluctuation solution theory for composition derivatives of solute/solvent infinite dilution activity coefficients. Suitable approximations are made for a single parameter characterizing solute/solvent interactions. Comparisons with available data show that the method is successful in describing a variety of observed mixed solvent solubility behavior, including nearly ideal systems with small excess solubilities, systems with solute‐independent excess solubilities, and systems deviating from these simple rules. Successful predictions for new solvent mixtures can be made using limited data from other mixtures. © 2009 American Institute of Chemical Engineers AIChE J, 2009

Quasi-thermodynamics of Viscous Flow of Electrolyte Solutions in Aqueous, Non-aqueous and Mixed Aqueous Solvents

Viscosity B-coefficients for cesium chloride and lithium sulfate in methanol + water mixtures at 25 and 35 °C are reported. A general treatment of the quasi-thermodynamics of viscous flow of electrolyte solutions is described. ΔG3Θ(1→1′), the contribution made to the Gibbs energy of activation of the solution by the influence of the solute on the solvent, is a function of solute–solvent interactions only; but, ΔH3Θ(1→1′) and ΔS3Θ(1→1′) also reflect the solvent–solvent interactions. In aqueous solution all alkali-metal ions except Li+ are sterically unsaturated, having solvent co-ordination numbers n<nmax , the maximum allowed sterically. Such complexes exchange molecules with the solvent more readily than saturated ones and have energy–reaction co-ordinate diagrams in forms that explain the negative B or ΔG3Θ(1→1′) values found in aqueous solution. Saturated complexes are the norm in non-aqueous solvents, and the ΔG3Θ(1→1′) values are determined mainly by the secondary solvation. Behavior in mixed solvents reflects the transition from aqueous to non-aqueous behavior across the range of solvent composition.

Macroscopically aligned films of discotic phthalocyanine by zone casting

This work describes a room temperature liquid crystalline phthalocyanine processed byusing zone casting. Highly oriented films that were uniform over several squarecentimeters were obtained on glass support from a mixed solvent (1:1 mixtureof toluene and ethylene chloride) solution. A columnar planar alignment ofColr in the film layers has been determined by optical polarized microscopy, ultraviolet–visibleabsorption, atomic force microscopy and x-ray diffraction studies. The films consist ofuniaxially oriented ribbon-like structures with molecular columns perpendicular to thesolidification direction. The pronounced alignment makes these thin films promising forapplication in optoelectronic devices.

Viscoelastic studies of some phenols from dielectric measurements

The variation of dielectric relaxation time with the viscosity of the medium is being exploited in drawing certain quantitative conclusions regarding molecular motion and intermolecular forces in liquids, liquid mixtures, dilute solutions and multi-component polar solutes in dilute solution. With no perfect empirical or theoretical equation in place for the variation of dielectric relaxation time with viscosity, the experimental investigations on different systems only can give an insight. In the present study the results of dielectric measurements carried out on pure samples of o-ethyl phenol, 2-n-butylphenol, 4-n-butylphenol, and 2,6-butylphenol in dilute solutions in different mixed solvents (benzene + paraffin) and on binary mixtures (1 : 1) of p-2-n-butylphenol + 4-n-butylphenol and p-bromonitrobenzene + 2,6-butylphenol, are reported. For comparison, the results on p-bromonitrobenzene + m-bromonitrobenzene as an example of mixture of non-associative liquids was also carried out and the results are presented. Different parameters determined using these dielectric measurements are also presented using different models and these studies indicate that the dielectric behavior at microwave frequencies favor the concept of dynamic viscosity and a single viscoelastic relaxation time for the system under study.

The interaction between trivalent 4f and 5f-block elements and thiocyanate ion

The formation constants of thiocyanate complexes of Eu(III) and Am(III) in trace concentrations were investigated in mixed solvent (CH3OH+H2O) solutions of different ionic strength. Furthermore, in paper electrophoresis, the moving velocities of the species of Eu(III) and Am(III) were investigated in 1.1M (H, Na)(SCN, ClO4) mixed solvent (CH3OH-H2O) solutions. The results showed that the difference between the velocities of Eu(III) and Am(III) is explained by the difference of the mean charges calculated by the formation constants of thiocyanate complexes of Eu(III) and Am(III) in the solution.

Calculation of solubility of solid solutes in mixed non-aqueous solvents within the limits of the theory of molecular association

A method for calculating the solubility of solid substances in mixed non aqueous solvents is proposed based on the theory of molecular association and a simple lattice model (ASL = Associated Solution + Lattice). This method provides the calculation of the solubility of solids in mixed non aqueous solvents using only the molecular association parameters and the value of the interchange energy ωAB that is derived from the phase equilibrium data in a mixed solvent.

Synthesis and Assembly of Magnetite Nanocubes into Flux-Closure Rings

Single-crystalline magnetite nanoparticles with a relatively narrow size distribution around 48 nm were solvothermally synthesized in a water−alcohol mixed solvent solution at 230 °C using ferrocene ((C5H5)2Fe), polyvinylpyrrolidone (PVP), and hydrogen peroxide (H2O2) as starting materials. These magnetite nanoparticles exhibited almost standard cube-like shape and were coated with a thick PVP layer (∼8 nm) to form a magnetite−PVP core−shell structure. Driven by strong magnetic dipolar attractions, magnetite nanocubes could be assembled into flux-closure rings, which consisted of several to dozens of nanocubes. The rings had one-particle annular thickness, and individual nanocubes were spaced fully together. It was found that only nanocubes, the average size of which was close to 50 nm, could be assembled into rings, while slightly smaller particles were aligned in dipolar chains, suggesting that ring self-assembly could be produced by the degradation of dipolar chains that were a metastable structure wit...

Dielectric relaxation in relation to viscosity of some organic molecules and some of their binary mixtures

The study of variation of dielectric relaxation time with the viscosity of the medium helps in drawing certain quantitative conclusions regarding molecular motion and intermolecular forces in liquids, liquid mixtures, dilute solutions and multi-component polar solutes in dilute solution. In the absence of a perfect empirical or theoretical equation for the variation of dielectric relaxation time with viscosity, the experimental investigations on different systems only can give an insight. In the present study the results of dielectric measurements carried out on samples of 2-chlorothiophene, 2-methyl benzaxazole, m-bromonitrobenzene, p-fluorophenyl acetonitile, p-bromonitrobenzene and 2-chloro-6-fluoro-benzaldehyde in dilute solutions in different mixed solvents (benzene + paraffin) and on binary mixtures (1:1) of p-fluorophenyl acetonitile + 2-butylphenol and 2-chloro-6-fluoro-benzaldehyde + o-ethylphenol, are reported. Different parameters determined using these dielectric measurements are also presented using different models and these studies indicate that the dielectric behavior at microwave frequencies favors the concept of dynamic viscosity and a single viscoelastic relaxation time for the system under study.

Dielectric constant dependence of formation constants: complexation of dioxovanadium(V) with cysteine

The complexation of dioxovanadium(V) with L-cysteine was investigated in mixed solvent systems of methanol + water and dioxane + water at 25°C and 0.1 mol dm−3 ionic media, using a combination of potentiometric and spectrophotometric techniques. Sodium perchlorate solution was used to maintain the ionic strength. The compositions of the formed complexes were determined, and it was shown that dioxovanadium(V), VO, forms two mononuclear species with the ligand. The stability constants of the complexes formed are given in the above mixed solvent media and interpreted. Linear relationships are observed when plotted log β versus 1/D, where β and D represent formation and dielectric constants, respectively. The results are discussed in terms of the effect on mole fraction of the solvent both for protonation and complexation of cysteine. An attempt has been made to ascertain the nature of the correction factor in determining the pH in the mixed solvent solutions and the effect of increasing organic solvent on log β is also considered.

Activity coefficients for salts in water–methanol mixed solvent solutions

The approach tested in this work consists in adapting the Pitzer model, initially designed for aqueous electrolyte solutions, to the case of solutions with a mixed solvent. This modified model was applied to KCl, LiCl, CsCl, RbCl, HCl, NaCl and NaBr in methanol–water mixtures at 25°C. The results show that the calculated mean activity coefficients of the electrolytes studied are in good agreement with experimental values obtained from the literature.

Modeling acid–base equilibria and phase behavior in mixed-solvent electrolyte systems

A comprehensive thermodynamic framework for mixed-solvent electrolyte systems has been applied to the simultaneous computation of phase behavior and acid–base equilibria. The computational approach combines an excess Gibbs energy model with a formulation for standard-state properties of individual species and an algorithm for speciation calculations. Using this framework, a consistent methodology has been established to calculate the pH of mixed-solvent solutions using a single, aqueous reference state. It has been shown that solid solubilities, vapor–liquid equilibria, solution pH and other properties can be reproduced for mixed solvents ranging from pure water to pure non-aqueous components and for solutes ranging from infinite dilution to the fused salt limit. In particular, the model has been shown to be accurate for mixtures containing hydrogen peroxide and ethylene glycol as solvents and various salts, acids and bases as solutes.