Cyclodextrins as Enhancers of the Aqueous Solubility of the Anthelmintic Drug Mebendazole: Thermodynamic Considerations

Summary.  Inclusion complexes of mebendazole with α-, β-, and γ-cyclodextrins, hydroxylpropyl-β-cyclodextrin (HP-β-CD), and methyl-β-cyclodextrin (Me-β-CD) were investigated employing the Higuchi and Connors solubility method. The solubility of mebendazole increased as a function of cyclodextrin concentration showing an A_L phase diagram indicating the formation of soluble complexes with 1:1 stoichiometry. The Gibbs free energies of transfer of the drug from aqueous solution to the cavity of cyclodextrin are negative and increase negatively with increasing cyclodextrin concentration. The solubility of mebendazole as well as the stability constant of its complex with Me-β-CD are found to be affected by the pH of the medium. The Me-β-CD cavity was found to have a greater affinity for the unionized mebendazole rather than the protonated one. Effects of methanol and temperature on these interactions were also investigated to gain further knowledge on the mechanism of the inclusion process. It was found that the interaction between the drug and the cyclodextrin is weakened as the medium becomes more apolar and the temperature increases. Moreover, the thermodynamic parameters for the binding were derived from the dependence of the stability constants on the temperature (van’t Hoff analysis). The formation of the inclusion complexes between the drug and β-CD or its derivatives was found to be enthalpy controlled, with |ΔH °| > T|ΔS °|. This suggests that hydrophobic and van der Waals interactions as well as solvent reorganization are the main driving forces. Furthermore, the size of the cavity of cyclodextrins plays an important role in the association process. Permanent address: Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt. E-mail: i.shehatta@uaeu.ac.ae Received November 30, 2001. Accepted (revised) December 27, 2001     

Thermodynamic Investigation of Phase Equilibria in Metal Carbonate–Water–Carbon Dioxide Systems

Summary.  Solubility measurements as a function of temperature have been shown to be a powerful tool for the determination of thermodynamic properties of sparingly-soluble transition metal carbonates. In contrast to calorimetric methods, such as solution calorimetry or drop calorimetry, the evaluation of solubility data avoids many systematic errors, yielding the enthalpy of solution at 298.15 K with an estimated uncertainty of ±3 kJ · mol⁻¹. A comprehensive set of thermodynamic data for otavite (CdCO₃), smithsonite (ZnCO₃), hydrozincite (Zn₅(OH)₆(CO₃)₂), malachite (Cu₂(OH)₂CO₃), azurite (Cu₃(OH)₂(CO₃)₂), and siderite (FeCO₃) was derived. Literature values for the standard enthalpy of formation of malachite and azurite were disproved by these solubility experiments, and revised values are recommended. In the case of siderite, data for the standard enthalpy of formation given by various data bases deviate from each other by more than 10 kJ · mol⁻¹ which can be attributed to a discrepancy in the auxiliary data for the Fe²⁺ ion. A critical evaluation of solubility data from various literature sources results in an optimized value for the standard enthalpy of formation for siderite. The Davies approximation, the specific ion-interaction theory, and the Pitzer concept are used for the extrapolation of the solubility constants to zero ionic strength in order to obtain standard thermodynamic properties valid at infinite dilution, T = 298.15 K, and p = 10⁵ Pa. The application of these electrolyte models to both homogeneous and heterogeneous (solid-solute) equilibria in aqueous solution is reviewed. Received June 26, 2001. Accepted July 2, 2001     

Solid-Solute Phase Equilibria in Aqueous Solutions XVII [I]. Solubility and Thermodynamic Data of Nickel(II) Hydroxide

Summary.  The solubility of nickel(II) hydroxide (theophrastite) in water was determined as a function of temperature and ionic strength by the pH variation method. In each experiment the inert electrolyte medium was made up with sodium perchlorate. The experimental data were thermodynamically analyzed, and the standard solubility constant was extrapolated to zero ionic strength with the specific ion-interaction equation. Furthermore, the standard molar Gibbs energy and the enthalpy of formation for theophrastite, β-Ni(OH)₂, were evaluated. For all calculations, ChemSage and its optimizer routine were used. Received October 25, 2001. Accepted October 29, 2001     

Thermodynamic Evaluation of Solid-State Reactions in which a Volatile Product is Formed

Summary. The use of equilibrium thermodynamics in describing interfacial reactions between non-ionic inorganic solids is demonstrated using examples of high-temperature interactions in the Ti–Si–N and Mo–Si–N systems. In the case of a diffusion-controlled process, solid-state reactions can be interpreted with chemical potential (activity) diagrams. The role of volatile reaction products formed during interaction in developing the diffusion zone morphology is analysed. The interfacial phenomena in systems based on dense Si₃N₄ and non-nitride forming metals can be explained by assuming a nitrogen pressure build-up at the contact surface. This pressure determines the chemical potential of Si at the interface and, hence, the reaction products in the diffusion zone.     

Spectroscopic Characterization of Some Tetradentate Schiff Bases and Their Complexes with Nickel,Copper and Zinc

Three ligands have been formed by the 1:2 molar condensation of o‐phenylenediamine with salicyldhyde, 2‐hydroxy‐1‐naphthaldhyde or o‐hydroxyacetophenone. The potentially tetradentate ligands are N,N′‐bis(salicyldhyde)‐o‐phenylenediamine(SalophH₂), N,N′‐bis(2‐hydroxy‐1‐naphthaldhyde)‐o‐phenylenediamine (NophH₂) and N,N′‐bis(o‐hydroxyacetophenone)‐o‐phenylenediamine (AophH₂), respectively. These ligands form complexes (1:1 molar ratio) with nickel, copper and zinc ions. The complexes have been characterized by IR, ¹HNMR, MS, uv/vis spectra in addition to elemental analysis. The spectral data of the ligands and their complexes with nickel, copper and zinc are discussed in connection with the structural changes which occur due to complexation.     

Solid-Solute Phase Equilibria in Aqueous Solutions XIV [1]. Thermodynamic Analysisof the Solubility of Hellyerite in Water

Summary.  The solubility of hellyerite, NiCO₃ · 6H₂O, in water was studied at different temperatures. From the experimental data obtained, a preliminary set of the thermodynamic quantities Δ_f G ^⊖, Δ_f H ^⊖, and S ^⊖ for hellyerite was derived using the ChemSage optimizer routine. Received January 16, 2001. Accepted January 18, 2001     

Solubilities of the Silver Halides in Aqueous Mixtures of Methanol,Acetonitrile, and Dimethylsulfoxide

Summary.  The solubilities of the silver halides in three non-aqueous solvents: methanol, acetonitrile, and dimethylsulfoxide, and in their aqueous mixtures, are reviewed. Values for the solubility product, K _SO , the enthalpies of solution, Δ _sol H ^o , and the equilibrium products for AgX ⁽ⁱ⁻¹⁾⁻ _i silver halide complexes, β _i , are listed and, where possible, compared. The solvent systems provide examples for three types of mixed aqueous solvent system: aqueous alcohol mixtures and aqueous mixtures with dipolar aprotic solvents that are weakly or strongly basic. The experimental data are discussed in terms of the solvation of the silver and halide ions in the mixed solvents. E-mail: Earle.Waghorne@ucd.ie Received September 30, 2002; accepted October 29, 2002 Published online April 7, 2003 RID="a" ID="a" Dedicated to Prof. Heinz Gamsj?ger on the occasion of his seventieth birthday     

The Solubility of Sodium Sulfate and the Reduction of Aqueous Sulfate by Magnetite under Near-Critical Conditions

The solubility of Na₂SO₄ (s) (thenardite) and the interactions between magnetiteand aqueous Na₂SO₄ near the critical point of water have been determined in azirconium-alloy flow reactor at temperatures 350°C t 375°C and isobaricpressures 190 p 305 bar. The experimental solubility data are describedwell as a function of temperature and solvent density ₁ byln x(Na₂SO₄, aq.) = –10.47 – 27550/T +(4805/T) ln ₁.The interaction between magnetite and Na₂SO₄ (aq.) was examined from 250 to370°C at molalities near the saturation composition of Na₂SO₄ (s). While no solidreaction products were observed, HS^– (aq.) was observed to form above 350°Cby sulfate reduction, as a product of the reaction8 Fe₃O₄(s) + Na₂SO₄ (aq.) + H₂O(l)= 12 Fe₂O₃ (s) + NaHS (aq.) + NaOH (aq.).The reduction reaction appears to be controlled by surface reaction kinetics, ata level well below the equilibrium molality of HS^– (aq.). Metallic iron reactedwith Na₂SO₄ (aq.) in a similar fashion at temperatures above 350°C, to yieldhigher molalities of HS^– (aq.).     

A Thermodynamic Frame for the Kinetics of Polymer Crystallization under Processing Conditions

Summary. A retrospective view is given on work, which has been carried out at the Johannes Kepler University during the last two decades on the structure formation in crystallizable polymers during their processing. Emphasis is laid on some useful principles lend from basic physical chemistry: use of the T,S-diagram and of the temperature dependent courses of (effective) surface tensions along coexistence lines of phases. These considerations should be helpful in creating an overview, where a deficiency of direct experimental crystallization kinetics data exists. For a series of industrially important, mostly fast crystallizing, polymers data are given in the present paper for the quiescent melt (temperature dependences of number densities of nuclei and of growth speeds). Critical minimum cooling speeds for bypassing crystallization are given on the basis of the given data. These critical cooling speeds vary by almost six decades from HDPE to i-PS. These results are also helpful in the formulation of a viable classification of materials in the light of their processing conditions. This classification includes metals and glass forming minerals as limiting cases for extremely fast and extremely slowly crystallizing materials.     

Solubility Behavior in Ternary Water-Salt Systems under Sub- and Supercritical Conditions

Summary.  Two main types of binary systems with distinctive solubility behavior under sub- and supercritical conditions were used to subdivide ternary water-salt systems into three classes. Characteristic features of solubility behavior and phase equilibria in ternary water-salt systems of each class at temperatures above 200°C are discussed on the basis of available experimental data and some conclusions obtained as a result of theoretical derivation of fluid and complete phase diagrams. Corresponding author. E-mail: Valyashko@IGIC.RAS.RU Received September 25, 2002; accepted (revised) November 28, 2002 Published online April 24, 2003 RID="a" ID="a" Dedicated to Prof. Dr. H. Gamsjaeger on the occasion of his 70^th birthday anniversary     

Solubility,similarity, and compatibility: A general-purpose theory for the formulator

After thousands of articles on solubility science (broadly including ‘similarity’ and ‘compatibility’) over the past decades, the formulator has been provided with surprisingly few tools that can help solve problems in the necessarily messy world of complex formulations. This failure of much of the academic enterprise has led to a culture of trial-and-error in formulation. Although a very few tools are of enduring value in solubility-related work, only one, currently, has a broad applicability across the range of solubility and compatibility problems faced by formulators. This tool is the Hansen Solubility Parameter (HSP) approach, which despite its many acknowledged faults and limitations is powerful and general enough to be able to guide users through formulation space with the help of on-line apps and data sets. The challenge for academics is not to fiddle with current tools but to think big and find new tools to exceed the power and generality of HSP.     

Diene,Alkyne, Alkene,and Alkyl Complexes of Early Transition Metals: Structures and Synthetic Applications in Organic and Polymer Chemistry

An unprecedented series of highly reactive alkene-and diene-complexes of the early transition metals (Groups 3A–5A of the periodic system) have been isolated recently. Diene complexes of this sort (M ? Ti, Zr, Hf, Nb, Ta) prefer, besides the (η⁴-s-cis-diene)metal structure, either a novel bent η⁴-metallacyclo-3-pentene structure or the unique (η⁴-s-trans-diene)metal structure. In bis(diene)metal complexes of Nb and Ta the η⁴-s-cis-dienes assume an unusual exo-endo (supine-prone) geometry. The M? C bonds in these diene-metal complexes generally exhibit highly polarized σ-bonding along with π-bonding character. The complexes therefore undergo a variety of regio- and stereoselective carbometalations with substrates containing C? C, C? O, or C? N multiple bonds. Examples of the products that can be obtained include ketones, vinyl ketones, unsaturated primary, secondary, and tertiary alcohols, as well as diols and unsaturated acids. Mechanistic studies on the stoichiometric and catalytic conversions of unsaturated hydrocarbons provides, inter alia, some insights into the course of polymerization reactions.     

Inclusion Complexation of Loratadine with Natural and Modified Cyclodextrins: Phase Solubility and Thermodynamic Studies

The extent and mode of solubility enhancement exerted by the cyclodextrins (α-, β-, γ-, and HP-β-CDs) on loratadine (Lort) have been experimentally measured under controlled conditions in buffered aqueous solutions. Rigorous nonlinear regression analysis of the phase solubility diagrams obtained in 0.1 mol⋅L⁻¹ phosphate buffer at pH=7.0 and 25 °C revealed the following: neutral Lort (pK _a =4.6) tends to form soluble 1:1 and 1:2 Lort/CD complexes with all four of the examined CDs, where complex stability follows the decreasing order β-CD>HP-β-CD>γ-CD>α-CD. The hydrophobic character of Lort constitutes about 66% of the driving force for complex formation whereas specific interactions contribute 11.2 kJ⋅mol⁻¹ towards the stability of the complexes. Thermodynamic studies showed that Lort/CD complex formation was favored by large enthalpic contributions but was impeded by negative entropic changes. Dissolution studies indicate that the dissolution rate of Lort from the freeze-dried Lort/β-CD complex is significantly higher than that of the corresponding physical mixture. Both DSC studies and molecular mechanical modeling of Lort/β-CD interactions were carried out to explore the possible formation of inclusion complexes.     

Solubility and thermodynamic function of a new anticancer drug ibrutinib in 2-(2-ethoxyethoxy)ethanol + water mixtures at different temperatures

Ibrutinib is a recently approved anticancer drug recommended for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. It has been reported as practically insoluble in water and hence it is available in the market at higher doses. Poor solubility of ibrutinib limits its development to oral solid dosage forms only. In this work, the solubilities of ibrutinib were measured in various 2-(2-ethoxyethoxy)ethanol (Carbitol) + water mixtures at T = (298.15 to 323.15) and p = 0.1 MPa. The solubility of ibrutinib was measured using an isothermal method. The thermodynamics function of ibrutinib was also studied. The measured solubilities of ibrutinib were correlated and fitted with Van’t Hoff, the modified Apelblat and Yalkowsky models. The results of curve fitting of all three models showed good correlation of experimental solubilities of ibrutinib with calculated ones. The mole fraction solubility of ibrutinib was observed highest in pure 2-(2-ethoxyethoxy)ethanol (2.67 · 10⁻² at T = 298.15 K) and lowest in pure water (1.43 · 10⁻⁷ at T = 298.15 K) at T = (298.15 to 323.15) K. Thermodynamics data of ibrutinib showed an endothermic, spontaneous and an entropy-driven dissolution behavior of ibrutinib in all 2-(2-ethoxyethoxy)ethanol + water mixtures. Based on these results, ibrutinib has been considered as practically insoluble in water and freely soluble in 2-(2-ethoxyethoxy)ethanol. Therefore, 2-(2-ethoxyethoxy)ethanol could be used as a physiologically compatible cosolvent for solubilization and stabilization of ibrutinib in an aqueous media. The solubility data of this work could be extremely useful in preformulation studies and formulation development of ibrutinib.     

Solubility and solution thermodynamics of 2, 6-bis (4-hydroybenzylidene) cyclohexanone in pure and binary solvents at various temperatures

Solubility of 2, 6-bis (4-hydroxybenzylidene) cyclohexanone (BHBC) in pure solvents such as 1,4-dioxane, methanol, 1-butanol, 1-propanol, ethyl acetate, acetone, tetrahydrofuran (THF), glacial acetic acid, dimethyl sulphoxide (DMSO) and binary solvents dimethyl formamide (DMF) and (1-Propanol + Tetrahydrofuran) were investigated by gravimetric method at different temperature range. The experiment solubility increases with increase in temperature in both pure and binary solvents. The Maximum solubility is found in DMF at 328.15 K and for binary solvent mixture i.e. 1-propanol and THF (0.9 mol fraction) it was maximum at 318.15 K. Further modified Apelblate and Buchowski-Ksiazczak models were used for the theoretical calculation of solubility of BHBC in pure as well binary solvents. A satisfactory correlation of these models with experimental data was observed. The solution thermodynamics parameters like enthalpies, Gibb's free energy of dissolution and entropy of solutions were calculated using Van't Hoff and Gibb's equation, which reveals the solvation mechanism is non-spontaneous and entropy driven.     

Comprehensive Model of Synthetic Bayer Liquors. Part 3. Sodium Aluminate Solutions and the Solubility of Gibbsite and Boehmite

Summary. A Pitzer model representing the thermodynamics of alkaline sodium aluminate solutions is presented. It constitutes a key part of our 10-component synthetic Bayer liquor model communicated in this series of papers. The present model calculates thermodynamic properties, such as heat capacities, osmotic coefficients, and densities, of these solutions as well as the solubilities of gibbsite and boehmite over temperature and concentration ranges of industrial interest.     

Speciation of Phytate Ion in Aqueous Solution. Thermodynamic Parameters for Zinc(II) Sequestration at Different Ionic Strengths and Temperatures

Results of an investigation on phytate interactions with zinc(II) cation in NaNO_3aq at different ionic strengths (0.1≤I/mol⋅L⁻¹≤1.0) are reported. Stability constants of various Zn _i H _j Phy^{(12−2i−j)−} species were determined by potentiometry (ISE-H⁺ glass electrode) and the corresponding formation enthalpies by direct calorimetric titrations. Data obtained were used to provide an exhaustive speciation scheme of zinc(II) in the presence of phytate, as well as a comprehensive representation of the binding ability of phytate toward zinc(II) in different conditions. Different pL₅₀ values [an empirical parameter already proposed, expressed as the −log ₁₀ C _Phy, where C _Phy is the total phytate concentration necessary to bind 50% zinc(II)] were calculated in several conditions, and equations were formulated to model its dependence on different variables, such as ionic strength, temperature and pH. Other empirical predictive relationships are also proposed. Previous contributions to this series reviewed in ref. [1].     

Solubility of celecoxib in carbitol + water mixtures at various temperatures: experimental data and mathematical modelling

ABSTRACT

A brief review on various solubilisation techniques of coxibs is provided and the solubility of celecoxib (CXB) in binary solvent mixtures of {carbitol (1) + water (2)} is reported at temperatures ranging from 298.2 to 313.2 K. Three cosolvency models, i.e. Yalkowsky model, Jouyban–Acree model and the Jouyban–Acree–van’t Hoff model, have been used for correlating the reported data, and the mean relative deviations are employed to evaluate the accuracy of the fitness. Solubilities are also predicted by the generally trained version of the Jouyban–Acree model and its combined model with Abraham solute parameters previously proposed for {carbitol (1) + water (2)} binary mixtures. Furthermore, the apparent thermodynamic properties of dissolution process of CXB in all -investigated solvents were calculated according to van’t Hoff and Gibbs equations.     

Chemical Speciation and Fractionation in Soil and Sediment Heavy Metal Analysis: A Review

Abstract

Today it is generally recognized that the particular behaviour of trace metals in the environment is determined by their specific physicochemical forms rather than by their total concentration. Several chemical speciation and fractionation methods for heavy metal analysis in soils and sediments have been and are still being developed and applied. They primarily are intended to understand the particular environmental behaviour of metals, present in a variety of forms and in a variety of matrices.

Analytical developments, modifications of existing methods, and recent new approaches are reviewed and discussed. Techniques used include chemical extractions, ion-exchange/gel chromatography, filtration, centrifugation and sieving, selective solvent extraction.

Moreover, the application of these various techniques in different research fields over the last years is explored. The value and the limitations of speciation and fractionation techniques applied in specific experimental work is outlined. It is discussed to what extent these methods have, up to now, filled in the expectations or have been satisfactory in particular applications.     

Raman Spectroscopy of Aqueous ZnSO4 Solutions under Hydrothermal Conditions: Solubility, Hydrolysis, and Sulfate Ion Pairing

Raman spectra have been measured for aqueous ZnSO₄ solutions under hydrothermal conditions at steam saturation to 244°C; solubility has been recorded as a function of temperature from 25 to 256°C. The high-temperature Raman spectra contained two polarized bands, which suggest that a second sulfato complex, possibly bidentate, is formed in solution, in addition to the 1:1 zinc(II) sulfato complex, which is the only ion pair identified at lower temperatures. Under hydrothermal conditions, it was possible to observe the hydrolysis of the zinc(II) aquo ion by measuring the relative intensity of bands due to SO ₄ ^2– and HSO ₄ ^– according to the equilibrium reaction Zn(OH₂)₆]²⁺ + SO ₄ ^2– [Zn(OH₂)₅OH]⁺ + HSO ₄ ^– The precipitate in equilibrium with the solution at 210°C could be characterized as ZnSO₄ · H₂O (gunningite) by x-ray diffraction (XRD) and Raman and infrared spectroscopy. At 244°C the equilibrium precipitate could be identified as ZnSO₄ (zincosite).