Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media

A temperature dependence of saturated vapor pressure of isavuconazole (IVZ), an antimycotic drug, was found by using the method of inert gas-carrier transfer and the thermodynamic functions of sublimation were calculated at a temperature of 298.15 K. The value of the compound standard molar enthalpy of sublimation was found to be 138.1 ± 0.5 kJ·mol−1. The IVZ thermophysical properties—melting point and enthalpy—equaled 302.7 K and 29.9 kJ mol−1, respectively. The isothermal saturation method was used to determine the drug solubility in seven pharmaceutically relevant solvents within the temperature range from 293.15 to 313.15 K. The IVZ solubility in the studied solvents increased in the following order: buffer pH 7.4, buffer pH 2.0, buffer pH 1.2, hexane, 1-octanol, 1-propanol, ethanol. Depending on the solvent chemical nature, the compound solubility varied from 6.7 × 10−6 to 0.3 mol·L−1. The Hansen s approach was used for evaluating and analyzing the solubility data of drug. The results show that this model well-described intermolecular interactions in the solutions studied. It was established that in comparison with the van’t Hoff model, the modified Apelblat one ensured the best correlation with the experimental solubility data of the studied drug. The activity coefficients at infinite dilution and dissolution excess thermodynamic functions of IVZ were calculated in each of the solvents. Temperature dependences of the compound partition coefficients were obtained in a binary 1-octanol/buffer pH 7.4 system and the transfer thermodynamic functions were calculated. The drug distribution from the aqueous solution to the organic medium was found to be spontaneous and entropy-driven.

Solubility of Rare Earth Chlorides in Ternary Water-Salt Systems in the Presence of a Fullerenol—C60(OH)24 Nanoclusters at 25 °C. Models of Nonelectrolyte Solubility in Electrolyte Solutions

The solubility in triple water-salt systems containing NdCl3, PrCl3, YCl3, TbCl3 chlorides, and water-soluble fullerenol C60(OH)24 at 25 °C was studied by isothermal saturation in ampoules. The analysis for the content of rare earth elements was carried out by atomic absorption spectroscopy, for the content of fullerenol—by electronic spectrophotometry. The solubility diagrams in all four ternary systems are simple eutonic, both consisting of two branches, corresponding to the crystallization of fullerenol crystal-hydrate and rare earth chloride crystal-hydrates, and containing one nonvariant point corresponding to the saturation of both solid phases. On the long branches of C60(OH)24*18H2O crystallization, a C60(OH)24 decreases by more than 2 orders of magnitude compared to the solubility of fullerenol in pure water (salting-out effect). On very short branches of crystallization of NdCl3*6H2O, PrCl3*7H2O, YCl3*6H2O, and TbCl3*6H2O, the salting-in effect is clearly observed, and the solubility of all four chlorides increases markedly. The four diagrams cannot be correctly approximated by the simple one-term Sechenov equation (SE-1), and very accurately approximated by the three-term modified Sechenov equation (SEM-3). Both equations for the calculation of nonelectrolyte solubility in electrolyte solutions (SE-1 and SEM-3 models) are obtained, using Pitzer model of virial decomposition of excess Gibbs energy of electrolyte solution. It is shown that semi-empirical equations of SE-1 and SEM-3 models may be extended to the systems with crystallization of crystal-solvates.

Solubility Data and Computational Modeling of Baricitinib in Various (DMSO + Water) Mixtures

The solubility and thermodynamic analysis of baricitinib (BNB) in various dimethyl sulfoxide (DMSO) + water mixtures were performed. The “mole fraction solubilities (xe)” of BNB in DMSO and water mixtures were determined at “T = 298.2–323.2 K” and “p = 0.1 MPa” using an isothermal saturation technique. “Hansen solubility parameters (HSPs)” of BNB, pure DMSO, pure water and “DMSO + water” mixtures free of BNB were also estimated. The xe data of BNB was regressed well by five different thermodynamics-based co-solvency models, which included “Apelblat, Van’t Hoff, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van’t Hoff models” with overall deviations of <5.0%. The highest and lowest xe value of BNB was computed in pure DMSO (1.69 × 10−1 at T = 323.2 K) and pure water (2.23 × 10−5 at T = 298.2 K), respectively. The HSP of BNB was found to be closer to that of pure DMSO. Based on activity coefficient data, maximum solute–solvent molecular interactions were observed in BNB-DMSO compared to BNB-water. The results of “apparent thermodynamic analysis” indicated endothermic and entropy-drive dissolution of BNB in all “DMSO + water” combinations including mono-solvents (water and DMSO). “Enthalpy-entropy compensation analysis” showed enthalpy-driven to be the main mechanism of solvation of BNB.

Determination and Calculation of Phase Equilibrium for Aqueous Ternary System (NH2)2CO+KCl+H2O at 283.15K

The solid-liquid phase equilibrium for ternary system (NH2)2CO+KCl+H2O was determined by isothermal saturation method at 283.15K under atmosphere pressure. The isothermal phase diagrams was drawn in according to the measured solubility data. There are one co-saturated point and two pure solids occurred in this ternary system. The solid phases were confirmed by Schreinemaker’s wet residue method and X-ray powder diffraction. Two thermodynamic models, Wilson model and NRTL model, were used to calculate the solubility data. The value of root mean-square deviation in Wilson model and NRTL model for this ternary system was 0.22 and 0.66 respectively, and the value of relative average deviation was 0.61% and 2.33% respectively, which indicated that the calculated data and the experimental results are nearly consistent.

МОДЕЛЮВАННЯ ІЗОТЕРМІЧНОГО РЕАКТОРА ДЛЯ НАСИЧЕННЯ САХАРОЗОЮ ЦУКАТІВ З ГАРБУЗА

Універсальна моделююча програма ChemCad дозволяє провести моделювання процесу насичення плодів гарбуза цукром. Результати моделювання дають можливість здійснення технологічного процесу з мінімальними енергозатратами та максимальним збереженням поживних речовин в готовому продукті, в якому єдиним консервантом буде цукор.За допомогою універсальної моделюючої програми ChemСad був змодельований ізотермічний реактор насичення частинок гарбуза цукром, який працює за умов постійної концентрації сахарози в сиропі і одночасним збільшенням концентрації сахарози в цукатах. Такий процес був змодельований стаціонарним з інтенсивним перемішуванням, працює в ізотермічному режимі і в якому кількість випаруваної води компенсує кількість виділеної води з цукату.Для моделювання необхідно було попередньо шляхом аналізу математичного опису знайти умови реалізації ізотермічного режиму, розробити математичне забезпечення для проектування реактора.Отримані числові значення результату моделювання, розрахункові та графічні залежності насичення цукатів сахарозою та проаналізовані отримані результати. Доведено, що проводити процес насичення цукатів цукром в стаціонарному режимі доцільно, з точки зору збереження органолептичних властивостей, оптимального насичення цукату, який буде довго зберігати свої властивості і не пліснявіти. ChemCad's universal simulator allows you to simulate the process of saturation of pumpkin fruit with sugar. The simulation results allow the implementation of a technological process with minimal energy consumption and maximum preservation of nutrients in the finished product, in which the only preservative is sugar. With the help of the universal simulation program ChemСad, an isothermal saturation reactor for sugar pumpkin particles was modeled, which operates under the constant concentration of sucrose in syrup and simultaneously increases the concentration of sucrose in candied fruits.Such a process was modeled by stationary with intense mixing, operating in isothermal mode and in which amount of evaporated water compensates for the amount of water extracted from candied fruit. For simulation, it was necessary to pre-analyze the mathematical description of the conditions for the implementation of the isothermal regime, to develop a mathematical support for the design of the reactor.For simulation, it was necessary to pre-analyze the mathematical description of the conditions for the implementation of the isothermal regime, to develop a mathematical support for the design of the reactor to include:- determination of the constant concentration of sugar in vaporized syrup at the end of the process, the flow of solution and vapor;- duration of sucrose saturation under stationary conditions;- definition of reactor design characteristics, diameter height and height of the liquid;Numerical simulation values, graphical and computational relationships are obtained, the result is analyzed.It is proved that the process of saturation of succulents with sugar in the steady state is advisable, in terms of preservation of organoleptic properties, optimum saturation of candied fruit, which will retain its properties and molds for a long time.

Solubility of ZrO2 in Cryolite-Based Molten Salt System

Electrolysis of cryolite-based molten salt is an important method for Al-Zr alloy production. The dissolution of ZrO2 in the melts effects current efficiency and energy consumption of the production process of Al-Zr alloy, so it is most importance to study the solubility of ZrO2 in the melts. In this paper, the solubility of ZrO2 in the cryolite-based molten salt of different composition at different temperatures was measured by isothermal saturation method. It was found that ZrO2 content increased rapidly in the initial stage, but the increase rate was very slow after two hours, so it was thought that ZrO2 was nearly saturation after two hour-after dissolution. The solubility of ZrO2 in cryolite-based molten salt increased markedly when increased the temperature and addition of CaF2. The solubility of ZrO2 in 2.2NaF·AlF3-Al2O3-CaF2 molten salt is similar with solubility of ZrO2 in the 2.2NaF·AlF3-CaF2, it is reach 5.5wt%.

Study of Solubility of WO3 in the NaCl-KCl-NaF-WO3 Molten Salt

The solubility of WO3 in NaCl-KCl-NaF-WO3 molten salt system was measured by isothermal saturation method. The results show that in the molten salt system when the temperature rise to 700 °C the saturation time of the WO3 dissolution time is 6 hours. When the temperature rise to 730 °C from 700 °C the saturation time of the WO3 dissolution time needs 80 minutes. As shown in the XRD pattern, there are NaCl, KCl, NaF, WO3, Na5W3O9F5, Na3WO3F3 and NaWO3F in the molten salt.

Effect of Temperature on Solubility of WO3 in the NaCl-KCl-NaF-WO3 Molten Salt

The solubility of WO3 in NaCl-KCl-NaF-WO3 molten salt system was measured by isothermal saturation method. The results show that in the molten salt system the solubility of WO3 increased with the increase of temperature from 700 °C to 820 °C, and the relationship between solubility and temperature is approximately linear. As shown in the XRD pattern, there are NaCl, KCl, NaF, WO3, Na5W3O9F5, Na3WO3F3 and NaWO3F in the molten salt, so the dissolution of WO3 is the result of both physical dissolution and chemical dissolution.

Utilization of the post-filtration lye from the SCS method of soda production

Utilization of the post-filtration lye from the SCS method of soda production The mutual solubility of salts in the NaVO3-NaNO3-H2O system was investigated at 293 - 323 K temperature range by the method of isothermal saturation of solutions. A fragment of the solubility polytherm for that system was plotted, based on the obtained data. The investigated system is a part of the quaternary NH4NO3-NaVO3-NH4VO3-NaNO3 system, and it is necessary for plotting the solubility isotherm as a planar projection according to Janecke, since it defines one edge of its square. Knowledge of the isotherm for that quaternary system is necessary to determine the optimal utilization conditions for the post-filtration lye, formed during the soda production from NaNO3 by the Solvay method, using NaVO3.

Zn2+-heparin interaction studied by potentiometric titration

Measurement of the decrease in pH that accompanies the addition of Zn2+ to heparin in solution provided an indirect method of examining cation-polyanion interaction. Construction of plots analogous to isothermal saturation binding plots revealed the existence, for defined conditions of interaction, of a [heparin]-independent direct proportionality between the fraction of the maximal pH change occurring and the [Zn2+]/[heparin disaccharide] ratio. This accords with results from polarimetric examination of Ca(2+)- and Cu(2+)-heparin interactions. It suggests that, under the conditions used, cation-heparin interaction may result in the formation of a complex that exists in a colloid-like phase, between which and the aqueous phase, exchange of cations does not follow simple solution-phase reversible equilibrium thermodynamic behaviour. The results suggest that the putative Zn(2+)-containing complex is less stable in the presence of NaCl than is the corresponding Ca(2+)-containing complex. Addition of Zn2+ to low concentrations of heparins is accompanied by the usual decrease in pH, followed by a removal of H+ from solution as the [Zn2+]/[heparin disaccharide] ratio increases, suggesting dissolution of the putative complex. This reversal of the initial pH change was not seen for most other cation-heparin interactions under the conditions studied.