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

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

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

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Scarabaeus sp.

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed

Novel Spiro-Derivatives of 1,3-Thiazine Molecular Crystals: Structural and Thermodynamic Aspects

Crystal structures of 10 spiro-derivatives of 1,3-thiazine were determined by X-ray diffraction technique. Molecular conformational states, packing architecture, and hydrogen bond networks were studied using graph set notations. Selected compounds were grouped within two classes with chains and dimer crystal structure organization. The sublimation thermodynamic aspects of the spiro-derivatives of 1,3-thiazine were investigated via temperature dependence of vapor pressure using the transpiration method. Thermophysical study of fusion processes of the molecular crystals was carried out and relationships between thermodynamic characteristics of sublimation (fusion) processes and crystal structure parameters were obtained. The influence of various molecular fragments on packing crystal energy was analyzed