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The solubility of griseofulvin in buffer solutions (pH 2.0 and 7.4), 1-octanol and hexane was measured in the temperature range 293.15–313.15 K by the shake flask method. It was found that griseofulvin is poorly soluble in aqueous buffer solutions (x≤8.63·10−7), while the best solubility is observed in 1-octanol (x≤6.56·10−4). The solubility evaluation in different solvents with the help of Hansen solubility parameters showed the consistency with the experimental data. The solubility was revealed to significantly depend on the dispersion interactions and polar bonds. The dissolution and solvation thermodynamic functions of the drug were calculated. The Gibbs energy and enthalpy of drug dissolution in aqueous and organic solvents are positive, which characterizes the dissolution process as hindered and endothermic. The van't Hoff and Apelblat equations gave good correlations when used for modeling the experimental solubility results. Based on the data on the solubility and thermophysical parameters of the compound, the temperature dependences of the activity coefficients were determined and the excess thermodynamic functions of dissolution were calculated. Positive deviation from ideality was observed in all the solvent-solute systems studied. The partition coefficients of the drug in the 1-octanol/buffer pH 7.4 system were obtained and the transfer thermodynamic functions were derived. It was established that the drug distribution from the aqueous solution to the octanol phase was thermodynamically favorable and endothermic. [ABSTRACT FROM AUTHOR]

The equilibrium solubility of climbazole (CLZ), an antifungal drug, was determined in buffers (pH 2.0; 7.4), hexane and 1-octanol within the temperature range 293.15–313.15 K. The measured solubility of the compound was correlated by the van't Hoff equation, modified Apelblat equation and two-suffix Margules model. Hansen solubility parameters show that 1-octanol and hexane can be considered relatively good solvents and water is a poor solvent for the drug studied. The molar heat capacity for CLZ was measured near the melting temperature. The theoretical ideal solubilities, activity coefficients and thermodynamic functions of dissolution and solvation of the drug were estimated. The temperature dependence of the CLZ partition coefficients were determined in a 1-octanol/buffer pH 7.4 system. The thermodynamic functions of the compound transfer from water to organic phase derived using partition coefficients and calculated based on the solvation parameters were in good agreement. [ABSTRACT FROM AUTHOR]

The saturated vapor pressure of the antifungal drug griseofulvin depending on temperature was measured by the transpiration method. The standard molar enthalpy of sublimation of the studied compound calculated from these data is (141.8 ± 1.2) kJ mol−1. Using thermogravimetric techniques, the vaporization enthalpy of drug was determined and the enthalpy of sublimation at reference temperature was calculated. It is shown that the values of this thermodynamic function derived by both these methods are equal within the experimental uncertainty. The space clusterization approach was applied for the estimation of thermodynamic sublimation functions of griseofulvin and structurally related compounds. In addition, the fusion temperature, enthalpy of fusion and heat capacity of the drug were measured by DSC. [ABSTRACT FROM AUTHOR]

The important physicochemical properties of three novel bioactive hybrid compounds with different groups (-CH3, -F and -Cl) were studied, including kinetic and thermodynamic solubility in pharmaceutically relevant solvents (buffer solutions and 1-octanol) as well as partition coefficient in system 1-octanol/buffer pH 7.4. The aqueous solubility of these chemicals is poor and ranged from 0.67 × 10−4 to 1.98 × 10−3 mol·L−1. The compounds studied are more soluble in the buffer pH 2.0, simulating the gastrointestinal tract environment (by an order of magnitude) than in the buffer pH 7.4 modelling plasma of blood. The solubility in 1-octanol is significantly higher; that is because of the specific interactions of the compounds with the solvent. The prediction solubility behaviour of the hybrid compounds using Hansen's three-parameter approach showed acceptable results. The experimental solubility of potential drugs was successfully correlated by means of two commonly known equations: modified Apelblat and van't Hoff. The temperature dependencies of partition coefficients of new hybrids in the model system 1-octanol/buffer pH 7.4 as a surrogate lipophilicity were measured by the shake flask method. It was found that compounds demonstrated a lipophilic nature and have optimal values of partition coefficients for oral absorption. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than fluconazole. In addition, the thermodynamic aspects of dissolution and partition processes have been examined. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than the reference drug. [ABSTRACT FROM AUTHOR]

The effect of the chemical nature of substituents (-H, -CH3-, -OCH3, -F and -Cl) introduced into the tricyclic fragment of hydrogenated pyrido[4,3-b]indoles on the compounds ability to positively modulate the activity of ionotropic glutamate AMPA receptors have been studied. The unsubstituted derivative, compounds with a methyl group and a fluorine atom were found to have the highest bioactivity in this test. The partition coefficients of the synthesized derivatives in the system 1-octanol/buffer pH 7.4 in the temperature range of 293.15-313.15 K have been measured. It has been found that as the lipophilicity of the compounds studied increases, the maximum biological activity is achieved at a higher concentration of the administered substance. The thermodynamic transfer functions of the studied substances from aqueous medium to organic phase have been calculated. [ABSTRACT FROM AUTHOR]

The inert gas transpiration technique was used for measuring the vapor pressures of the following biologically active compounds: 4-aminobenzoic acid, nicotinic acid, 4-aminobenzamide, 4-pyridinecarboxamide, N-(2-chloro-3-pyridinyl)-benzenesulfonamide, 4-nitro- N-2-thiazolyl-benzenesulfonamide, and 4-amino- N-(5-methyl-3-isoxazolyl)-benzenesulfon-amide in the appropriate temperature ranges. Differential scanning calorimetric analysis was applied to obtain the temperature and molar enthalpy of melting of the compounds studied. Standard molar enthalpies, entropies, and Gibbs energies of sublimation were derived at T = 298.15 K from the temperature dependences of the vapor pressure of the compounds. The obtained results allowed the estimation of the relationship between the sublimation thermodynamic parameters and the thermophysical properties of the substances. Correlation equations were used for calculating the saturated vapor pressures on the basis of the melting temperatures, sublimation enthalpies, and physicochemical HYBOT descriptors. [ABSTRACT FROM AUTHOR]

The temperature dependencies of the saturated vapor pressure for antituberculous drug compounds: pyrazinecarboxamide and three isonicotinic acid hydrazides were obtained using the method of inert gas-carrier transfer. The standard sublimation molar enthalpies, entropies and Gibbs energies were derived at T = 298.15 K. The temperature and fusion molar enthalpy of the compounds were measured using the differential scanning calorimetry technique. The influence of the structure of the studied compounds on the crystal lattice energy and volatility was analyzed. It was estimated that the saturated vapor pressure of the studied substances decreases when the molecule polarizability and donor-acceptor ability increase. [ABSTRACT FROM AUTHOR]

Novel drug-like spiro-derivatives of 1,3-thiazine were synthesized. Thermodynamic aspects of sublimation processes of the studied compounds were determined using temperature dependencies of the vapor pressures. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. Solubilities of spiro-derivatives in buffer and hexane were measured in the temperature interval 298.15-315.15 K by an isothermal saturation method. Temperature dependencies of partition coefficients for the studied substances in the systems buffer/organic phase were obtained. Thermodynamic functions describing the solubility, solvation and distribution processes were calculated. The diagram enabling analysis of the mechanism of transfer process was applied. [ABSTRACT FROM AUTHOR]

Interaction between fullerene C60 and N,N-dialkyl-substituted anilines was studied by gas–liquid chromatography (GLC) and titration calorimetry. The GLC study was performed at 140–200°C in the poly(tetramethylbenzene) solvent with ultra-high solubility of C60. No interaction of the C60–aniline type was registered under such conditions. Calorimetric titration performed at 25°C in a non-aromatic solvent confirmed the lack of complex formation. Minute exoeffect registered is explained by suppressing of the rotation motion of the C60 molecules accompanied by energy dissipation for the aniline environment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]