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Abstract: The thermodynamic aspects of sublimation processes of three sulfonamides with the general structures C6H5–SO2NH–C6H4–R (R=4-NO2) and 4-NH2–C6H4–SO2NH–C6H4–R (R=4-NO2; 4-CN) were studied by investigating the temperature dependence of vapor pressure using the transpiration method. These data together with those obtained earlier for C6H5–SO2NH–C6H4–R (R=4-Cl) and 4-NH2–C6H4–SO2NH–C6H4–R (R=4-Cl; 4-OMe; 4-C2H5) were analyzed and compared. A correlation was derived between sublimation Gibbs free energies and the sum of H-bond acceptor factors of the molecules. Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol (as phases modeling various drug delivery pathways) were investigated and corresponding thermodynamic functions were calculated as well. Thermodynamic characteristics of the sulfonamides solvation were evaluated. Also in this case a correlation between solubility/solvation Gibbs free energy values and the sum of H-bond acceptor factors was observed. For the sulfonamides with various substituents at para-position the processes of transfer from one solvent (water or buffer) to n-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to the interpretation of only the Gibbs free energy of transfer (extensively used for pharmaceuticals in the form of the partition coefficient, log P), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs. [Copyright &y& Elsevier]

Abstract: Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP) were measured, and standard thermodynamic functions of sublimation were calculated (FBF: ; ; ; DIF: ; ; ; FBP: ; ; ). Thermochemical parameters of fusion process for FBF were obtained, and evaporation enthalpy was estimated from fusion and sublimation enthalpies. Temperature dependencies of the solubility in buffer solutions (pHs 2.0 and 7.4), n-Octanol, and n-Hexane were measured, and solution and solvation thermodynamic functions were calculated. The transfer thermodynamic functions from n-Hexane to solvents used (imitating specific “drug–solvent” interaction), and from buffer solutions to n-Octanol (imitating partitioning/distribution processes) were analyzed. Specific/non-specific “drug–solvent” interaction ratios in terms of solvation enthalpies were estimated. All studied solutions are characterized by prevalence of non-specific “drug–solvent” interactions. A difference exists between mechanisms of partitioning and distribution of studied drugs. [Copyright &y& Elsevier]

Abstract: Saturated vapor pressures for a number of parabens (methyl- (MePB); ethyl- (EtPB), n-propyl- (PrPB) and n-butyl- (BuPB)) were obtained and from their respective temperature dependences the sublimation enthalpy, , and sublimation entropy, , as well as their respective relative fractions in the process calculated. The sublimation enthalpies are: (MePB)=98.8±0.8; (EtPB)=100.9±0.7; (PrPB)=123.7±0.6; (BuPB)=108.4±0.8kJmol-1. The obtained values are discussed with regard to X-ray data from the literature. Theoretical calculations of the respective crystal lattice energies were carried out and compared to the experimental data. The following parameters were analyzed: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy of the crystals; (b) contributions of the different fragments of the paraben molecules to the packing energy; (c) influence of bias of the supposed C–H distances on the result of the calculation procedure. Enthalpies of evaporation were estimated from the measured enthalpies of sublimation and enthalpies of fusion, and compared with literature data. Moreover, the thermodynamic functions of solvation of the molecules in water and in a number of n-alcohols were evaluated. The thermodynamic terms (Gibbs energy, enthalpy and entropy) of the solvation process were split up in their respective specific and nonspecific fraction, and these values compared for all combinations of parabens and solvents. The influence of mutual saturation of the phases in the water–octanol system on the partitioning process of the molecules is also discussed. [Copyright &y& Elsevier]

Naproxen was studied by classical thermoanalytical methods, namely sublimation calorimetry, solution calorimetry and the solubility method. Temperature dependence of a saturated vapor pressure was obtained and the sublimation enthalpy, ΔHsub0, and entropy, ΔSsub0, and their relative fraction of the total process were calculated. These parameters yielded for naproxen were compared to the respective data of other naphthalene derivatives. The crystal lattice energy of naproxen was calculated by two force fields (Gavezzotti et al. and Mayo et al.) and compared to the experimental data. Contributions of different motifs of the naproxen molecule to the total packing energy were analyzed. The Gibbs energy of solvation as well as enthalpic and entropic terms thereof in aliphatic alcohols have been studied for naproxen, and compared to model substances and other non-steroid anti-inflammatory drugs (benzoic acid, diflunisal and flurbiprofen). The major driving force of the solvation process is the enthalpy. The respective contributions of the specific and the non-specific solvation interactions in terms of absolute and relative values have been investigated. [Copyright &y& Elsevier]

Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, Δ H , as well as the entropies of sublimation, Δ H , and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, Δ G , and the transfer Gibbs energy from water to octanol, Δ G . Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropy-compensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed. [ABSTRACT FROM AUTHOR]

Three independent methods (sublimation, solubility and solution calorimetry) were used to study the dissolution and solvation processes of diflunisal (DIF) and flurbiprofen (FBP). Thermodynamic functions for the sublimation of DIF and FBP were obtained. Concentrations of saturated solutions and standard solution enthalpies of DIF and FBP in aliphatic alcohols and individual organic solvents were measured. Correlation analysis between: (a) the thermodynamic functions for a substance in various solvents, and (b) the same functions for different compounds was carried out. The investigated substances can be arranged with increasing Gibbs energy of solvation as follows: benzoic acid

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]

Highlights: [•] Thermodynamic characteristics of sublimation process were investigated for 2-, 3- and 4-acetamidobenzoic acids. [•] Thermophysic parameters of melting processes were determined and enthalpies of vaporization were calculated for the isomers. [•] Sublimation thermodynamic parameters were compared with crystal structures of the isomers. [Copyright &y& Elsevier]

Abstract: Temperature dependencies of vapor pressure were obtained by flow inert gas-carrier transfer method for 2-, 3- and 4-hydroxybenzamide in the temperature interval (from 302.15 to 345.15)K, (from 367.65 to 396.15)K and (from 360.15 to 420.65)K, respectively. The thermodynamic functions of sublimation process were estimated on the basis of the experimental results. The fusion processes of the compounds under investigation were studied using the differential scanning calorimetry method. The comparative analysis of parameters describing packing density of molecules in crystal lattices was done and thermodynamic and thermophysical parameters of sublimation and fusion processes were analyzed. The influence of crystal density calculated based on the X-ray data on sublimation enthalpy under standard conditions was found. For some benzamide derivatives the sublimation enthalpy was observed to depend on the melting point temperature. [Copyright &y& Elsevier]

• 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]

The saturated vapor pressures of 4 nonaromatic bicyclic 1,3-thiazine and 1,3-selenazine derivatives have been measured by the method of transpiration by inert gas-carrier in the temperature range of 308–392 K. Based on the experimental data the thermodynamic functions of sublimation have been calculated. The sublimation enthalpies of the compounds vary from 104 to 150 kJ mol −1 depending on the chemical nature of the substituent in the aryl moiety and the heteroatom in the bicyclic fragment. The crystal lattice energy of thiazines decreases with the introduction of substituents in the following order: cyano > acetyl > isopropyl. New approach has been suggested to evaluating sublimation enthalpy of the studied and structurally related compounds by using clusterization of the space of experimental points. [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]

Influence of a structural modification on thermodynamic aspects of solubility and solvation processes of the 1,2,4-thiadiazole drug-like compounds in pharmaceutically relevant solvents n -hexane and 1-octanol was investigated. The solubility of the compounds in 1-octanol does not substantially depend on the nature and position of the substituent in the phenyl moiety. In n -hexane, however, the introduction of any substituent in the phenyl ring of the 1,2,4-thiadiazole molecule reduces the solubility in the solvent. In order to rationalize the relationships between the structure of 1,2,4-thiadiazoles and their solubility, the latter was considered in terms of two fundamental processes: sublimation and solvation. It was found that for the most of the compounds the solubility change in both solvents is a consequence of competition between the sublimation and solvation contributions, i.e. the introduction of substituents leads to growth of the sublimation Gibbs energy and increase in the solvation Gibbs energy. Thermodynamic parameters of the transfer process of the compounds from n -hexane to 1-octanol, which is a model of the blood–brain barrier (BBB), were also analyzed. [ABSTRACT FROM AUTHOR]

Temperature dependences of saturated vapor pressure for crystalline phases of 2-ethyl-4-pyridinecarbothioamide (ethionamide) and two parent compounds 2- and 4-pyridinecarbothioamide isomers were measured by the transpiration method. The results were used to determine the standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K. HYBOT descriptors application has shown an increase in the donor–acceptor ability of the molecules of the studied compounds to form hydrogen bonds to result in their crystal lattice energy growth. The obtained standard molar sublimation enthalpies have been compared with the literature results for 2- and 4-substituted pyridine isomers . [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]

Highlights: [•] Temperature dependencies of saturated vapor pressure of new bicyclo-derivatives were obtained. [•] Thermodynamic functions of sublimation and solvation were calculated. [•] The correlations between thermodynamic functions and molecular descriptors are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The article deals with the study of two polymorphic modifications in the space groups P21/c (white form) and P21/n (yellow form) of the tolfenamic acid. It also describes how the white form vapor pressure temperature dependence was determined by using the transpiration method and how thermodynamic parameters of the sublimation process were calculated. We have estimated the difference between the crystal lattice energies of the two polymorphic forms by solution calorimetry and found that the crystal lattice energy of the yellow form is 6.7±1.2kJmol−1 higher than that of the white form, whereas Gibbs free energies of the forms obtained from the vapor pressure temperature dependence are practically the same. The modifications under consideration are monotropically related. From the practical point of view, the white form is more preferable due to its lower crystal lattice energy and better performing procedure. We have also studied the solubility, solvation and transfer processes of the tolfenamic acid white form in buffers (with various values of pH and ionic strengths), n-hexane and n-octanol. The thermodynamic parameters of the investigated processes have been discussed and compared with those determined for others fenamates. In the study we estimated specific and non-specific contributions of the solvation enthalpic term of the fenamate molecules with the solvents as well. The driving forces of the transfer processes from the buffers with pH 7.4 and different ionic strengths to n-octanol were analyzed. It was found that the relationship between the enthalpic and entropic terms depends essentially on the ionic strength. For the considered fenamates the transfer processes of the neutral molecules and the ionic forms are enthalpy-determined, whereas for the niflumic acid this process is entropy-determined. [Copyright &y& Elsevier]