Solubility Parameter of Gatifloxacin and Its Correlation with Antibacterial Activity

The solubility parameter of gatifloxacin was calculated theoretically by Fedors’ method and also determined experimentally using the standard solubility method. The molar volume of gatifloxacin was determined experimentally by the flotation method. Three solvents, ethyl acetate, propylene glycol and water were used to prepare nine binary mixtures having different solubility parameter values varying from 8.9 to 23.4 H. The δ ₂ solubility parameter of gatifloxacin was found to be 12.4 H. The cumulative transport of gatifloxacin from the binary solvent mixtures (ethyl acetate–propylene glycol and propylene glycol–water) exhibited an inverse parabolic relationship to the solubility parameter of the solvent mixtures. Transport studies revealed that the extent of gatifloxacin rejection from solvent mixtures was dependent on its solubility parameter and system composition. In the selected organisms (bacteria), a minimum zone of inhibition was observed in a solvent mixture having the solubility parameter nearest to the solubility parameter of gatifloxacin. Two models were employed for the evaluation of the antibacterial activity of gatifloxacin in binary mixtures.     

Revisiting the Solubility Concept of Pharmaceutical Compounds

Summary.  The kinetic and thermodynamic solubilities of Roche (Ro) pharmaceutical compounds were determined by HPLC, titrimetry, and UV/Vis spectroscopy in aqueous buffers and in non-buffered systems. For kinetic solubility, a turbidimetric method that allows the rapid determination of solubilities using small amounts of compounds (5–50 mg) was used. Two types of precipitation were observed during the kinetic solubility determinations: i) a disperse precipitation where the solution became foggy with very small particles uniformly distributed in the solution, and ii) discrete precipitation characterized by formation of crystals that rapidly sediment. The thermodynamic solubility was determined by shake flask and titrimetrically using a pH-STAT. The pH-STAT titrimetric method for the pH-thermodynamic solubility profile determination eliminates the buffer species and represents a new way to approach the solubility characterization of pharmaceutical compounds. The strengths of the turbidimetric method for determining the kinetic solubility are its rapidity, minimal compound requirements, and suitability for high throughput screening. The limitations are that the maximum solubility is limited to less than 100 mg · cm⁻³, and the precipitation of trace impurities cannot be distinguished from precipitation of the analyte. The pH-STAT titrimetric approach for the thermodynamic solubility has a lower throughput and is suitable for the characterization of the lead candidate. It is not limited in its solubility range and provides a common basis for the comparison of the solubility values at different pH values in contrast to traditional buffered systems. Received August 21, 2000. Accepted (revised) February 5, 2001     

The Solubility and Solvation of Salts in Mixed Nonaqueous Solvents. 2. Potassium Halides in Mixed Protic Solvents

The solubilities of potassium fluoride, chloride, and bromide in ethanol, formamide, and N-methylformamide and in binary mixtures of these solvents were determined at 25°C. The standard molar Gibbs energies of solution, Δ_soln G ^o, in the neat solvents were related to their hydrogen bonding abilities. The values of Δ_soln G ^o in the mixtures were fitted with expressions of the quasilattice quasichemical theory, and the preferential solvation of the ions was thereby established.     

Influence of the Cation on the Solubility of CO<Subscript>2</Subscript> and H<Subscript>2</Subscript> in Ionic Liquids Based on the Bis(trifluoromethylsulfonyl)imide Anion

Experimental values for the solubility of carbon dioxide and hydrogen in three room temperature ionic liquids based on the same anion—(bistrifluoromethylsulfonyl)imide [Ntf₂]—and three different cations—1-butyl-3-methylimidazolium, [C₄mim], 1-ethyl-3-methylimidazolium, [C₂mim] and trimethyl-butylammonium, [N₄₁₁₁]—are reported between 283 and 343 K and close to atmospheric pressure. Carbon dioxide, with a mole-fraction solubility of the order of 10⁻², is two orders of magnitude more soluble than hydrogen. The solubility of CO₂ is very similar in the three ionic liquids although slightly lower in the presence of the [C₂mim] cation. In the case of H₂, noticeable differences were observed with larger mole fraction solubilities in the presence of [N₄₁₁₁] followed by [C₄mim]. All of the mole-fraction solubilities decrease with increasing temperature. From the variation of Henry’s law constants with temperature, the thermodynamic functions of solvation were calculated. The precision of the experimental data, considered as the average absolute deviation of the Henry’s law constants from appropriate smoothing equations, is always better than ±1%.     

Inverse gas chromatography. Relationship between mass activity coefficient and flory-huggins interaction parameter in the examination of petroleum pitches

Summary The use of the basic relations for the calculation of the weight fraction activity coefficient Ω ₁ ^∞ and the Flory-Huggins interaction parameter ϰ ₁₂ ^∞ requires the knowledge of the density and the molecular mass of the stationary phase. As these data are often inaccessible the use of a simplified equation is examined. The errors generated during the calculation of ϰ ₁₂ ^∞ and solubility parameter δ₂ are presented and discussed. All experimental data were collected for the series of fractions separated from high-boiling vacuum distillation residues of petroleum.     

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     

Thermodynamics of Mixing and Solvation of Ibuprofen and Naproxen in Propylene Glycol + Water Cosolvent Mixtures

By using the van’t Hoff and Gibbs equations, solubility data of ibuprofen (IBP) and naproxen (NAP) determined at several temperatures in propylene glycol (PG) + water (W) cosolvent mixtures were used to evaluate the Gibbs energies, enthalpies, and entropies of solution, mixing and solvation. The solubilities are greater in pure PG and lower in W in both cases at all studied temperatures. These results clearly show that a cosolvent effect is present in these systems. The solvation of these drugs was greater in W compared to PG, and it was lower in the cosolvent mixtures compared with the pure solvents. By means of an enthalpy-entropy compensation analysis, non-linear ΔH _soln^o versus ΔG _soln^o compensation plots were obtained, with negative and positive slopes if all of the composition intervals are considered. Accordingly, it follows that at low PG solvent fractions the dominant factor for the solubility of IBP and NAP in this cosolvent system is the entropy, probably due to loosening of the water structure caused by the addition of the cosolvent.     

Aqueous solubility calculation of aromatic acids within a wide temperature range using a modified regular solution model

Abstract  

The modified RSFH model, based on the regular solution theory coupled with the Flory-Huggins entropy term, was extended to calculate the solubility of aromatic acids in water within wide temperature ranges. The aqueous solubility data on aromatic acids from the published literature were assembled and validated. A total of 1,009 aqueous solubility data points for 25 aromatic acids within the temperature range of 273–463 K were selected for modeling. The calculation results showed that the solubility of aromatic acids in water could be well represented by the proposed four-parameter solution model within a wide temperature range. The overall absolute average deviation (δ _AAD) is 6.76%. The estimated cohesive energies of the aromatic acids were found to be about 20–30 kJ mol⁻¹. For the majority of the aromatic acids investigated, the cohesive energy could be considered as a constant. Strong temperature dependency, however, was also observed for a few aromatic acids, and misleading results may be obtained if this dependency is neglected. The model also has a certain prediction ability and could be extrapolated to a high temperature range where no experimental solubility data are available.     

The Solubility of the Chloromethanes in Water

Summary.  There are more than 150 papers that report on the solubility of the four chloromethanes in water. Volume 62 of the Solubility Data Series compiles and evaluates the papers concerned with the liquid–liquid solubility of the chloromethanes with water. A similar evaluation has not been carried out for the vapor–liquid solubility at a partial pressure up to the saturation vapor pressure of the four chloromethanes. This paper uses the liquid–liquid evaluated solubility values to calculate vapor–liquid Henry’s constants. They are compared with a compilation of Henry’s constants with good agreements between the calculated constants and the median of the compiled constants. It is believed that the calculated constants are a reliable set of values to use for the vapor–liquid solubility of the chloromethanes in water. E-mail: hlclever@worldnet.att.net Received October 11, 2002; accepted October 22, 2002 Published online April 24, 2003 RID="a" ID="a" Dedicated to Prof. Dr. Heinz Gamsj?ger on the occasion of his 70^th birthday     

Estimation of Solubility of Carbon Dioxide in Polar Solvents

The solubility of CO₂ in polar solvents is poorly predicted by all estimation methods that use only properties of the pure components. It is thought that this is because CO₂ molecules, although they do not have a permanent dipole moment, behave like electrical multipoles as a consequence of their strongly polar bonds. An equation, proposed in a previous paper, for estimating the activity coefficient of a nonpolar gas dissolved in a polar liquid is modified by adding a term containing the quadrupole moment of the gas molecule. Errors in estimating gas solubilities on that basis are less than 20%, except for the solvents in which specific interactions (e.g., acid–base interactions) are present.     

Solubility of CO2 in CO2-philic oligomers; COSMOtherm predictions and experimental results

We report the solubility of carbon dioxide in four physical solvents and compare our data to predicted phase behavior using the conductor-like screening model for real solvents (COSMO-RS) formalism. The solubility data are presented in pressure-composition (Px) diagrams as well as Henry's law coefficients on a wt% basis at 298.15 K. The oligomers presented in this study are poly ethylene glycol di-methyl ether (PEGDME), perfluoro polyether (PFPE), poly di-methyl siloxane (PDMS), and poly propylene glycol di-methyl ether (PPGDME), which is a new solvent designed for this application by our group. These oligomers had 2–5 repeat units. We assess these four oligomers for capturing CO₂ from high-pressure streams. The COSMO-RS formalism is able to qualitatively and to some extent quantitatively describe solubilities of CO₂ in each of the oligomers.     

Solubility parameter determination of cationic surfactants by inverse GC

Summary The solubility parameters of cationic surfactants were obtained using the inverse gas chromatographic technique. The surfactants didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and dodecyl pyridinium chloride were used as stationary phase and retention data of different probe solutes were measured at different temperatures. The results were analysed by the combination of Flory-Huggins and Hildebrand theories, and the solubility parameters of the surfactants were obtained in a range of temperatures between 80–120°C.     

Solubility of bosentan in {propylene glycol + water} mixtures at various temperatures: experimental data and mathematical modelling

Solubility measurements were performed for bosentan (BST) in binary mixtures of propylene glycol (PG) and water at atmospheric pressure within the temperature range, T = 293.2 – 313.2 K by employing a shake-flask method. Generated solubility data were correlated with Jouyban-Acree-van’t Hoff model and the accuracies of the predicted solubilities and model performance were illustrated by mean relative deviations (MRD). Furthermore, the apparent thermodynamic properties of BST dissolving in all the mixed solvents were calculated, and the obtained results show that the dissolution process is endothermic. By using the inverse Kirkwood–Buff integrals, it was observed that BST is preferentially solvated by water in water-rich solvent mixtures and preferentially solvated by PG (as a cosolvent) in the composition range of 0.20 < x₁ < 1.00 at 298.2 K.     

Solubility in the ternary system CaSO<Subscript>4</Subscript> + Na<Subscript>2</Subscript>SO<Subscript>4</Subscript> + H<Subscript>2</Subscript>O at 298.15 K

The solubility in the ternary system, aqueous mixture of CaSO₄ and Na₂SO₄, at T = 298.15 K comprises five different salts: calcium sulfate dihydrate, mirabilite, thenardite, glauberite and labile salt. Using the Extended Pitzer’s Ion Interaction model for pure and mixed electrolyte solutions and criteria of phase equilibria, predicted solubility behavior of salts was compared with experimental results from literature. The agreement between calculated and experimental solubilities was excellent in the ionic strength range up to 10.9062 mol kg⁻¹.     

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     

Solubility of Zinc Silicate and Zinc Ferrite in Aqueous Solution to High Temperatures

Crystalline zinc silicate, Zn₂SiO₄, and zinc ferrite, ZnFe₂O₄, were prepared and characterized. The solubilities of these phases were measured using flow-through apparatus from 50 to 350 °C in 100 °C intervals over a wide range of pH. Both solid phases dissolve incongruently, presumably to form ZnO(s) and Fe₂O₃(s) (or the corresponding hydroxide phases at low temperature), respectively. The respective concentrations of zinc(II) and iron(III) matched those of ZnO(cr) and Fe₂O₃(s) (≥150 °C) reported in the literature, whereas the corresponding Si(IV) and Zn(II) concentrations were at least an order of magnitude below the solubility limits for their pure oxide phases. Therefore, the solubility constants for zinc silicate and ferrite were determined with respect to the known solubility constants for ZnO(cr) and Fe₂O₃(s) (≥150 °C), respectively, and the corresponding concentrations of Si(IV) and Zn(II) measured in this study. The results of independent experiments, as well as those reported in the literature provide insights into the mechanism(s) of formation of zinc silicate and ferrite in the primary circuits of nuclear reactors. D.A. Palmer is retired.     

Solubility of nonpolar gases in tetrahydropyran at 0 to 30°C and 101.33 kPa partial pressure of gas

Solubility measurements of several nonpolar gases (He, Ne, Ar, Kr, Xe, H₂, D₂, N₂, CH₄, C₂H₄, C₂H₆, CF₄, and SF₆) in tetrahydropyran at the temperature range 0 to 30°C and 101.33 kPa partial pressure of gas are reported. Thermodynamic functions for the solution process (Gibbs energy, enthalpy, and entropies) at 25°C are evaluated from the experimental values of the solubility of gases as mole fraction and their variation with the temperature. Lennard-Jones 6–12 pair potential parameters for tetrahydropyran are estimated by using the scale particle theory (SPT); and experimental solubilities are compared with the calculated values using this model. Experimental solubilities of gases in tetrahydropyran and intermolecular potential parameters are compared with those obtained for the same gases in other cycloethers.     

Solubility of 1-Pentene Ice in Liquid Nitrogen and Argon at the Standard Boiling Points of the Solvents

The solubilities of 1-pentene ice in liquid nitrogen at a temperature of 77.4 K and in liquid argon at 87.3 K have been measured by the filtration method. The 1-pentene content in solution was determined using gas chromatography. The experimental value of the mole fraction solubility of 1-pentene ice in liquid nitrogen at 77.4 K is: (1.28±0.25)×10^–7 and (4.11±0.44)×10^–7 in liquid argon at 87.3 K. The Preston–Prausnitz method was used for calculation of the solubilities of 1-pentene ice in liquid nitrogen in the temperature range 64.0–90.0 K and in liquid argon in the temperature range 84.0–90.0 K. The parameters l ₁₂ were also calculated. At 90.0 K liquid argon is the better solvent for 1-pentene ice than is liquid nitrogen.     

Solubility of dilute SO2 and CO2 in dimethyl sulfoxide

The solubility of SO₂ and CO₂ in dimethyl sulfoxide has been determined in the temperature range from 293.15 to 313.15?K and partial pressure of SO₂ from 0.15 to 2.62?kPa, and the partial pressure of CO₂ from 5 to 18?kPa. A solubility model is proposed and the solubilities calculated by the model show good agreement with the experimental data.