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• Solubility of carvedilol was determined in buffers (pH 2.0 and 7.4), hexane and 1-octanol. • Driving forces of dissolution in aqueous and organic solvents were revealed. • Ideal solubility and activity coefficient of drug of the compound were evaluated using thermophysical parameters. • Distribution coefficients of CVD were measured in 1-octanol/water and hexane/water systems. • Thermodynamic functions of transfer process in the modeling two-phase systems were calculated. The key physico-chemical properties for pharmaceutical design as solubility and distribution coefficients of cardiovascular carvedilol (CVD) in modeling solvents and biphasic systems were determined using the classic shake flask method in the temperature range (293.15–313.15) K. The drug solubility in 1-octanol and hexane was measured at first time. The equilibrium mole fraction solubility of CVD at reference temperature was changed in following order: 1-octanol (2.79∙10-3) > hexane (4.56∙10-6) > buffer pH 2.0 (3.39∙10-6) > buffer pH 7.4 (1.53∙10-7). Solubility pH-profile was characterized a weak solubility in acidic media and very poor solubility in neutral. The experimental lipophilic values logD O/B (1.83 and 2.36 at buffer solution pH 2.0 and 7.4, respectively) were shown the excellent penetration power into both the circulatory system and the entire intestinal tract. The temperature dependences of the CVD distribution coefficients in 1-octanol/buffer and hexane/buffer two-phase systems at pH two values (2.0 and 7.4) were considered from the thermodynamic view point. Thermodynamic functions of solubility and transfer processes were calculated and analyzed. Thermophysical parameters of the compound were used for estimation of the ideal solubility and activity coefficients. Moreover partial excess thermodynamic functions of CVD dissolution in saturated solutions, demonstrating the positive deviation real solvents from ideality, are also evaluated in detail. The data obtained will be in demand both for the creation of conceptually new dosage forms of carvedilol with improved bioavailability, and for constructing structure–property correlations in a number of structure-like compounds. [ABSTRACT FROM AUTHOR]

• The solubility of AETH in five solvents were measured at different temperatures. • The solubility data were correlated by the Apelblat and van't Hoff models. • The Hansen solubility parameters for AETH and selected solvents were estimated. • The ideal solubility and the activity coefficients of AETH were calculated. • Vapor pressures of AETH were determined by transpiration method. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer pH 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. [ABSTRACT FROM AUTHOR]

Highlights: [•] The vapor pressures of novel bicyclo-derivatives of amine were measured. [•] Thermodynamic functions of sublimation were calculated. [•] The influence of substituent structure and chemical nature on the vapor pressure was studied. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

• Solubility of fluconazole was measured in buffers (pH 1.2, 2.0, 7.4), hexane and 1-octanol. • The melting temperature and enthalpy of fluconazole were obtained. • The vapor pressure and sublimation thermodynamics were determined. 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. [ABSTRACT FROM AUTHOR]

• The solubility of Aceclofenac in aqueous and organic solvents were measured. • Sublimation enthalpy of drug was determined by transpiration method. • The distribution coefficients of Aceclofenac in systems 1-octanol/buffer were obtained. • Thermodynamics parameters of solubility, solvation and transfer for drug were calculated. Equilibrium solubility of aceclofenac - a non-steroidal anti-inflammatory drug – has been measured using the shake-flask method between T = (293.15–313.15) K in four pharmaceutically important solvents: buffers (pH 2.0 and 7.4), 1-octanol and hexane. The activity coefficients at infinite dilution of the compound in each of the solvents and molar excess thermodynamic functions have been calculated. It has been established that the entropy term of the Gibbs energy makes the main contribution to the deviation from ideality in the studied drug – solvent systems. The saturated vapor pressures of aceclofenac have been measured in the temperature range T = (355.15–372.15) K, using the transpiration method and the sublimation enthalpy, at T = 298.15 K, has been found to be 102.7 kJ·mol−1. Based on the dissolution and sublimation data, the drug solvation enthalpies in the studied solvents have been obtained. The distribution coefficients of aceclofenac have been determined in the systems 1-octanol/buffer (pH 2.0 and 7.4) within the temperature range T = (293.15–313.15) K. The process of the drug distribution in the studied systems is characterized by favourable energy of transfer from the aqueous phase to the organic one and by positive values of transfer enthalpy and entropy. It has been found that the increase in the drug hydration in buffer solutions reduces the drug distribution coefficients. [ABSTRACT FROM AUTHOR]

• Vapor pressure of drug were determined and sublimation thermodynamics were evaluated. • Solubility of nifedipine was measured in buffers (pH 2.0 and 7.4), n-hexane and 1-octanol. • Thermodynamic parameters of solubility and solvation were calculated. • Solid state of compound was characterized by DSC and PXRD. • Transfer process nifedipine between aqueous and organic phases was discussed. The saturated vapour pressure of the cardiovascular drug nifedipine is measured within the temperature range (390.15–404.15) K by the inert gas-carrier method. The thermodynamic functions of sublimation of the compounds are calculated at a reference temperature. The standard molar enthalpy of nifedipine sublimation is found to be equal to 144.8 kJ∙mol−1. The drug solubility in solvents modeling various media of the human body is determined in the temperature range (293.15–313.15) K. In the ascending order of solubility values of the studied compound, the solvents can be arranged as follows: buffer pH 7.4, buffer pH 2.0, n -hexane, 1-octanol. The solute–solvent intermolecular interactions are discussed based on the thermodynamic functions of solubility, solvation and transfer. [ABSTRACT FROM AUTHOR]

Highlights • Vapor pressures of Clonixin were determined by transpiration method. • The solubility of drug in four solvents were measured at different temperatures. • The distribution coefficients of Clonixin in system 1-octanol/ buffer were obtained. • Thermodynamics parameters of solubility, solvation and transfer for Clonixin were calculated. Abstract 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. [ABSTRACT FROM AUTHOR]

• Solubility of cardiovascular sotalol hydrochloride were determined in buffers, 1-octanol and n-hexane. • Agreement between the calculated pH-solubility profile of the drug and the experimental water solubility was obtained. • The temperature dependences of the distribution coefficients of drug in model systems were measured. • Thermodynamic functions of drug dissolution and transfer in solvents used were calculated. The shake-flask method was used to determine the solubility of sotalol hydrochloride (STL), a cardiovascular drug, in solvents modeling a variety of body media within the temperature range (293.15–313.15) K. In the descending order of the drug solubility the solvents can be arranged as follows: buffer pH 2.0, buffer pH 7.4, 1-octanol, n-hexane. The experimental values of solubility of the drug in aqueous solvents agree well with the calculated values of the pH-solubility profile. The study shows that the maximum solubility of the salt is observed within the pH range from 2.9 to pH max equal to 6.1. Temperature dependencies of the STL distribution coefficients were obtained in 1-octanol/buffer pH 7.4 and n-hexane/buffer pH 7.4 systems. Since the values of the partition coefficients of hydrophilic STL are low, it was concluded that the diffusion through the lipid biolayer of cell membranes was unfavorable and that the paracellular transport of the drug molecules might prevail. The thermodynamic functions of dissolution and transfer were calculated and discussed taking into account the physicochemical properties of STL and the solvents used. [ABSTRACT FROM AUTHOR]

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 logD O/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 logD H/B  < 1. According to the obtained partition coefficients (logP O/B ), bicyclic derivatives with alkyl substitutents are the most lipophilic ones. The logP O/B values are consistent with those calculated using the HyperChem program (RMSE = 0.5 log units). It is shown that the lipophilicity of the studied compounds with an azabicyclo[3,3,1]nonane fragment is higher than that of their structural analogues with a spiro-bicycle. The transfer process of compounds from the aqueous phase to the organic one is characterized as spontaneous, endothermic and entropy-driven. The effect of solvation enthalpies of the studied compounds in buffer pH 7.4, 1-octanol and hexane on partition coefficients has been revealed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• The thermophysical behavior of antiarrhythmic Dofetilide was studied. • Drug solubility were measured in buffer solutions (pH 7.4 and 2.0), 1-octanol, hexane. • The distribution coefficients of DFT in two biphasic systems were obtained. • Thermodynamics parameters of transfer for drug were calculated. 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. [ABSTRACT FROM AUTHOR]

• The saturated vapor pressures of 5 biologically active pyrido[4,3-b]indoles measured. • The sublimation thermodynamic functions of the compounds studied calculated. • The space clusterization approach used for estimation the enthalpies of sublimation. • The sublimation, dissolution and solvation processes studied by diagram method. 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. [ABSTRACT FROM AUTHOR]