Felodipine–diazabicyclo[2.2.2]octane–water (1/1/1)

The title compound, C₁₈H₁₉Cl₂NO₄·C₆H₁₂N₂·H₂O, is a cocrystal hydrate containing the active pharmaceutical ingredient felodipine and diazabicyclo[2.2.2]octane (DABCO). The DABCO and water molecules are linked through O—H...N hydrogen bonds into chains around 2₁ screw axes, while the felodipine molecules form N—H...O hydrogen bonds to the water molecules. The felodipine molecules adopt centrosymmetric back‐to‐back arrangements that are similar to those present in all of its four reported polymorphs. The dichlorophenyl rings also form π‐stacking interactions. The inclusion of water molecules in the cocrystal, rather than formation of N—H...N hydrogen bonds between felodipine and DABCO, may be associated with steric hindrance that would arise between DABCO and the methyl groups of felodipine if they were directly involved in hydrogen bonding.     

The Polymorphism of Glycine. Thermochemical and structural aspects

X-ray, DSC and solution calorimetric investigations were carried out for α-, β- and γ-modifications of glycine. Particular attention was paid to kinetic and thermochemical aspects of γ- → α-phase transition. The temperature of this phase transition turned out to be sensitive to a) conditions under which the crystals of the γ-modification were grown, b) tempering of crystals c) form (geometry) of crystals. Kinetics of this phase transition of single crystals of γ-phase in rhomboedric form can be described by the equation for two-dimension nuclei growth, whereas for crystals of triangle geometry the equation for three dimension growth is valid. On the basis of energy parameters describing growth of α-form in γ- →α-phase transition, the kind of structure defects, which are responsible for this phase transition, was estimated. Taking into account the Δ_sol H _m, the absolute values of the lattice energies of the investigated polymorphs indescending order are follows: γ->α->β-modification. The obtained results are discussed with respect to the peculiarity of the crystal lattice structures, particularly the network of hydrogen bonds. The β-modification of glycine is monotropically related to the other forms, whereas γ-and α-polymorphs are enantiotropically-related phases. This revised version was published online in July 2006 with corrections to the Cover Date.     

Inclusion complex formation of ��- and ��-cyclodextrins with riboflavin and alloxazine in aqueous solution: thermodynamic study

Possibility of encapsulation of riboflavin and alloxazine by ??- and ??-cyclodextrins in aqueous solution was studied by ¹H NMR and solubility methods. Thermodynamic parameters of 1:1 inclusion complex formation (K, ??_cG⁰, ??_cH⁰ and ??_cS⁰) were obtained and analyzed in terms of influence of reagent??s structure on complexation process. It was shown that ??-cyclodextrin displays low binding affinity to riboflavin and alloxazine. On the contrary, ??-cyclodextrin forms with riboflavin and alloxazine more stable inclusion complexes. Binding is accompanied by the negative enthalpy and entropy changes that are determined by predominance of van der Waals interactions and possible H-bonding. The presence of ribityl substituent in riboflavin molecule prevents the deep penetration of this compound into macrocyclic cavity. Proposed on the basis of ¹H NMR data the partial insertion of the hydrophobic part of riboflavin and alloxazine molecules into the ??-cyclodextrin cavity causes the enhancement of aqueous solubility of the encapsulated substances. In comparison with ??-cyclodextrin, the solubilizing effect of ??-cyclodextrin is more pronounced due to its higher binding affinity to alloxazine and riboflavin.     

Thermodynamics of potassium diclofenac salt aqueous solutions at various temperatures

Solution and dilution enthalpies of aqueous solutions of potassium diclofenac salt (K_DC) were measured by an isoperibolic calorimeter at 298.15 and 318.5 K. Heat capacities of the solutions with concentrations 0.002–0.09 mol kg⁻¹ were obtained at the temperature interval of 288.15–318.15 K using a scanning adiabatic microcalorimeter. The virial coefficients were derived from Pitzer’s model, and the excess thermodynamic functions of both the solvent and the solute of the solution were calculated. The concentration and temperature dependencies of thermodynamic characteristics of the solution were analyzed and discussed.     

The thermodynamic characteristics of sublimation of fenamate molecular crystals

The temperature dependences of vapor pressure were determined by the transpiration method and the thermodynamic functions of sublimation were calculated for six molecular crystals from the group of nonsteroidal antiinflammatory drugs, for niflumic, flufenamic, tolfenamic, mefenamic, and N-phenylanthranylic acids and diphenylamine. The influence of substituents on the enthalpies of sublimation of compounds of this class was studied. A correlation was observed between the enthalpies of sublimation under standard conditions and the temperatures of fusion.     

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 and thermodynamic study of solubility,partition and solvation of climbazole

Journal of Thermal Analysis and Calorimetry - The equilibrium solubility of climbazole (CLZ), an antifungal drug, was determined in buffers (pH 2.0; 7.4), hexane and 1-octanol within the...     

New Solid Forms of Nitrofurantoin and 4-Aminopyridine Salt: Influence of Salt Hydration Level on Crystal Packing and Physicochemical Properties

The crystallization of the poorly soluble drug nitrofurantoin (NFT) with 4-aminopyridine (4AmPy) resulted in three multicomponent solid forms with different hydration levels: anhydrous salt [NFT+4AmPy] (1:1), salt monohydrate [NFT+4AmPy+H₂O] (1:1:1), and salt tetrahydrate [NFT+4AmPy+H₂O] (1:1:4). Each salt was selectively prepared by liquid-assisted grinding in the presence of acetonitrile or ethanol/water mixture at a specific composition. The NFT hydrated salts were characterized using single crystal X-ray diffraction. The [NFT+4AmPy+H₂O] salt (1:1:1) crystallized as an isolated site hydrate, while the [NFT+4AmPy+H₂O] salt (1:1:4) crystallized as a channel hydrate. The dehydration processes of the NFT salt hydrates were investigated using differential scanning calorimetry and thermogravimetric analysis. A powder dissolution experiment was carried out for all NFT multicomponent solid forms in pH 7.4 phosphate buffer solution at 37 °C.     

Study of Three-Dimensional,Surface, and Linear Structures of Allotropic Carbon: Diffraction Spectra of Auger Electron Energy Losses

A theoretical approach is developed for determining the parameters of nanoscale crystal structures using diffraction spectra of Auger electron energy losses. The approach is based on modeling the radial distribution functions of atoms while allowing for the sizes of atomic structures, and on the geometry of surfaces of three-dimensional, surface, and linear objects intersecting with a sphere. Using the example of allotropic carbon phases, it is shown that the proposed technique allows assessment of a studied object’s thickness and the depth of the analyzed signal output with an accuracy of one atom’s diameter.