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This paper presents new experimental data on some key physicochemical properties of original bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl) hexanamide (AETH). Thermal analysis of the compound under study has been carried out using differential scanning calorimetry and thermogravimetric techniques. AETH solubility data in five pharmaceutically relevant solvents in the temperature range from 288.15 to 318.15 K have been obtained by the classic saturation shake-flask method. The bioactive compound has poor solubility in hexane and buffer solutions, while it is slightly soluble in selected alcohols. The experimental solubility results have been correlated by means of modified Apelblat and van’t Hoff equations. The selected thermodynamic models produced acceptable results. The Hansen solubility parameters and their components for AETH and solvents have been evaluated by using the van Krevelen–Hoftyzer atomic group contribution method. The ideal solubility and the solution activity coefficient at equilibrium in the selected solvents have been quantified based on experimental values of melting enthalpy and temperature. All the investigated solutions exhibit a positive deviation from ideality with the maximal solubility in alcohols. The equilibrium vapor pressure of the compound studied has been determined as a function of temperature in the range of 433.15–454.15 K by the transpiration method. The standard thermodynamic parameters of AETH sublimation have been calculated. It has been concluded that the high crystal lattice energy value equal to 131.5 kJ/mol is the dominant factor determining the poor solubility of the bioactive compound.

The saturated vapor pressure of Clonixin has been measured by the transpiration method in the temperature range of 419.15–443.15 К, and the thermodynamic functions of sublimation have been calculated. It has been found that the energy of the compound crystal lattice is equal to 108.4 kJ·mol−1. The drug solubility in solvents imitating biological media of the body (buffer pH 2.0 and 7.4, 1-octanol, hexane) and the distribution coefficients in the systems 1-octanol/buffer (pH 2.0 and 7.4) have been determined by the shake-flask method in the temperature range of 293.15–313.15 К. The compound solubility values in these solvents lie within the interval from 1.78·10−4 to 8.01·10−2 mol/l. The coefficients of the drug distribution from buffer pH 2.0 in 1-octanol are one order of magnitude higher than from buffer pH 7.4. Based on the experimental data, the thermodynamic functions of the drug dissolution, transfer and solvation have been calculated in the chosen solvents.

The apparent distribution coefficients of the potential bioactive compounds of the N-aryl-(3-sulfur-1-azabicyclo[3,3,1] non-2-ylidene) amine series in organic solvent/buffer pH 7.4 systems at five temperatures from 293.15 to 315.15 K have been determined by the shake-flask method. The logDO/B values of substances between 1-octanol and the aqueous phase range from 1.76 to 2.06 and at 298 K decrease depending on the chemical nature of the substituents of the phenyl fragment in the following order: cyan- > ethyl- > acetyl- > methyl-, chloro- > isopropyl-. The replacement of 1-octanol by hexane shifts the equilibrium of the substances from the organic phase to the buffer and the resulting values logDH/B

The thermophysical properties of the antiarrhythmic drug Dofetilide have been studied and it has been established that it represents a mixture of polymorphic modifications. The drug solubility in the following aqueous and organic solvents modeling physiological media has been determined: buffer pH 7.4, buffer pH 2.0, 1-octanol and hexane in the temperature range of 293.15–313.15 K by the shake-flask method. The drug solubility changes from 2.4 10−6 to 12.7 10−3 mol·L-1 depending on the solvent chemical nature and at the temperature 298.15 K decreases in the following order: buffer pH 2.0 > buffer pH 7.4 > 1-octanol > hexane. The distribution coefficients of Dofetilide in two-phase systems of 1-octanol/buffer (pH 7.4 and 2.0) and hexane/buffer (pH 7.4 and 2.0) have been determined within the temperature range of 293.15–313.15 K. In all the studied systems, an increase in the buffer solution acidity from pH 7.4 to pH 2.0 lowers the drug distribution coefficient. The experimental data and the calculated thermodynamic functions of Dofetilide transfer from aqueous phase to organic solvent have been discussed based on the compound protolytic properties.

Three biologically active selenium bicyclic compounds – N-aryl-(3-seleno-azabicyclo[3.3.1]non-2-ylidene)amines were synthesized. The effect of the substances structure on their protolytic properties was investigated. The substance solubility in hexane and pharmaceutically relevant buffer solutions (pH 2.0 and pH 7.4) was measured in the temperature range of 293.15–313.15 K by the saturation shake-flask method. Temperature dependences of the distribution coefficients of the compounds in the two-phase systems “organic solvent (octanol, hexane)/buffer solution” were obtained. Thermodynamic parameters of distribution process were calculated.

Vapor pressure of thioacetazone (TAZ) has been determined in the temperature range of 404.15–429.15 K by the transpiration method. The obtained data were used to calculate the standard molar enthalpy of sublimation that was found to be 164.1 kJ/mol at T = 298.15 K. The drug solubility was measured at seven temperatures from 288.15 to 318.15 K in modeling solvents: octanol, hexane and aqueous buffers pH 2.0 and 7.4 by the saturation shake-flask method by using spectrophotometric analysis. It has been found that TAZ has poor solubility in hexane and buffer solutions and limited solubility in octanol. The experimental data were well correlated by van’t Hoff and modified Apelblat equations. A temperature dependence of TAZ partition coefficient in the octanol/buffer pH 7.4 system has been derived. The partition coefficient value in this system (logP = 1.82) refers to the optimal interval for oral absorption drugs. The thermodynamic parameters of sublimation, solubility, solvation and transfer have been determined based on experimental data. The dominant effect of enthalpy and entropy contributions to the Gibbs energy of the investigated processes has been revealed.

The transpiration method was used to measure the vapor pressures as a function of temperature of the following antimicrobial drugs: ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin. Based on these results standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K were calculated and a correlation between the crystal lattice energy and the saturation vapor pressure in a number of fluoroquinolones was found. The thermophysical characteristics of the compounds studied were determined by DSC. The influence of different structural fragments of molecules substituents and the effects of hydrogen bonds in crystal lattices on the sublimation enthalpy was discussed.

The solubility of the antifungal drug fluconazole in buffer solutions of different acidity (pH 1.2, 2.0 and 7.4), 1-octanol and hexane in the temperature range (293.15–313.15) K is determined by the isothermal saturation method. The solubility of the compound in selected solvents increases as follows: hexane, buffer pH 7.4, buffer pH 2.0, 1- octanol, buffer pH 1.2, and does not exceed 0.2 mol·l−1. The temperature dependence of fluconazole saturated vapor pressure is obtained by the transpiration method. The sublimation enthalpy of the compound equals 131.4 ± 0.9 kJ·mol−1. Based on the HYBOT descriptors, it is shown that it is possible to estimate the sublimation enthalpy of compounds structurally similar to fluconazole.

The saturated vapor pressure of 5 biologically active compounds of the series of hydrogenated pyrido[4,3-b]indoles were measured using the transpiration method in the temperature range of (427.15–461.15) K. Based on the experimental data the thermodynamic functions of sublimation were calculated. The sublimation enthalpies of the compounds vary from 143.1 to 167.3 kJ·mol−1. It has been shown that the thermodynamic functions of sublimation can be estimated by the space clusterization approach for the studied and structurally related compounds The diagram approach has been used to study the effect of the chemical nature of substituents on sublimation, dissolution and solvation of the compounds in solvents modelling different biological media: buffer pH 7.4, 1-octanol and n-hexane. It has been established that structural modification of the molecules through the introduction of a fluorine atom into the indole fragment reduces the sublimation and solvation terms of the Gibbs energy of dissolution in buffer pH 7.4 and hexane, improving the solubility.

The solubility values of pyrazinamide, isoniazid, and p-aminobenzoic acid in buffers (рН 2.0 and 7.4) and octanol were measured in the temperature range of 293.15 to 313.15 K. The dissolution Gibbs energy, enthalpy, and entropy were calculated. The dissolving process was endothermic and enthalpy-determined. The activity coefficients of the compounds at infinite dilution were determined based on the solubility data and thermophysical parameters. A positive deviation from the ideality was observed in all the solutions. A common tendency of the solubility increase with a decrease in the activity coefficients at T = 298.15 K was revealed for the investigated solute-solvent systems. The excess thermodynamic solubility functions were calculated from the temperature dependences of the activity coefficients. The solvation processes were found to have a considerable influence on the solubility of the substances in solutions studied.

Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer рН 7.4 has been measured within the range of (9.02 · 10−5 to 1.05 · 10−4) mol/l. The relationship between the chemical nature and the structure of the aryl substituents and the solubility parameter was investigated. The fusion temperatures, enthalpies and entropies have been determined experimentally. The influence of thermophysical characteristics and lipophilicity on the solubility was studied using regression analysis. The calculations by the solubility/lipophilicity equation showed an overall improvement of the predictions equal to 0.5 log units. It was concluded that the solvation has a considerable influence on the solubility of the compounds under consideration. It was also determined that the alkyl- and halogen-derivatives solubility values correlate with HYBOT descriptors characterizing the (donor + acceptor) properties of the substances. The thermodynamic parameters of the solubility process were calculated using the temperature dependences. The study also revealed that the solubility of the bicyclic compounds is characterized by high endothermicity of the processes and negative entropies.

The vapor pressures of five novel bicyclic heterocycle derivatives were measured over the temperature 341.15 to 396.15 K using the transpiration method by means of an inert gas carrier. From these results the standard enthalpies and Gibbs free energies of sublimation at the temperature 298.15 K were calculated. The effects of alkyl- and chloro-substitutions on changes in the thermodynamic functions have been investigated. Quantitative structure–property relationship on the basis HYBOT physico-chemical descriptors for biologically active compounds have been developed to predict the sublimation enthalpies and Gibbs free energies of the compounds studied.

Temperature dependences of partition coefficient for 11 drug-like spiro-derivatives of 1,3-thiazine in the system aqueous phosphate buffer/organic phase (hexane, octanol) have been determined over the temperature range (293.15 to 315.15) K by the isothermal saturation method. The effects of aliphatic chain substituent structure and introduction of oxygen, chlorine, bromine and fluorine atoms on the partitioning processes of the substances studied were examined. It has been established that among the substances investigated halogen derivatives possess the lowest partition coefficients in buffer/hexane system and the highest ones in buffer/octanol system. Regularities between the partition coefficients and the descriptors reflecting the capability of the solutes to undergo specific and nonspecific interactions with solvent molecules were revealed. The thermodynamic functions describing the partitioning process were calculated. It was found that differences in the partition coefficients depend on the enthalpies of transfer.