N. G. Manin

Salicylamide Cocrystals: Screening, Crystal Structure, Sublimation Thermodynamics, Dissolution, and Solid-State DFT Calculations

A new cocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoic acid (B) has been obtained by the DSC screening method. Thermophysical analysis of the aggregate [A:B] has been conducted and a fusion diagram has been plotted. Cocrystal formation from melts was studied by using thermomicroscopy. A cocrystal single-crystal was grown and its crystal structure was determined. The pattern of noncovalent interactions has been quantified using the solid-state DFT computations coupled with the Bader analysis of the periodic electron density. The sublimation processes of A-B cocrystal have been studied and its thermodynamic functions have been calculated. The classical method of substance transfer by inert gas-carrier was chosen to investigate sublimation processes experimentally. The lattice energy is found to be 143 ± 4 kJ/mol. It is lower than the sum of the corresponding values of the cocrystal pure components. The theoretical value of the lattice energy, 156 kJ/mol, is in reasonable agreement with the experimental one. A ternary phase diagram of solubility (A-B-ethanol) has been plotted and the areas with solutions for growing thermodynamically stable cocrystals have been determined.

Cocrystal screening of hydroxybenzamides with benzoic acid derivatives: A comparative study of thermal and solution-based methods

The main problem occurring at the early stages of cocrystal search is the choice of an effective screening technique. Among the most popular techniques of obtaining cocrystals are crystallization from solution, crystallization from melt and solvent-drop grinding. This paper represents a comparative analysis of the following screening techniques: DSC cocrystal screening method, thermal microscopy and saturation temperature method. The efficiency of different techniques of cocrystal screening was checked in 18 systems. Benzamide and benzoic acid derivatives were chosen as model systems due to their ability to form acid-amide supramolecular heterosynthon. The screening has confirmed the formation of 6 new cocrystals. The screening by the saturation temperature method has the highest screen-out rate but the smallest range of application. DSC screening has a satisfactory accuracy and allows screening over a short time. Thermal microscopy is most efficient as an additional technique used to interpret ambiguous DSC screening results. The study also included an analysis of the influence of solvent type and component solubility on cocrystal formation.

Pharmaceutical Cocrystals of Diflunisal and Diclofenac with Theophylline

Pharmaceutical cocrystals of nonsteroidal anti-inflammatory drugs diflunisal (DIF) and diclofenac (DIC) with theophylline (THP) were obtained, and their crystal structures were determined. In both of the crystal structures, molecules form a hydrogen bonded supramolecular unit consisting of a centrosymmetric dimer of THP and two molecules of active pharmaceutical ingredient (API). Crystal lattice energy calculations showed that the packing energy gain of the [DIC + THP] cocrystal is derived mainly from the dispersion energy, which dominates the structures of the cocrystals. The enthalpies of cocrystal formation were estimated by solution calorimetry, and their thermal stability was studied by differential scanning calorimetry. The cocrystals showed an enhancement of apparent solubility compared to the corresponding pure APIs, while the intrinsic dissolution rates are comparable. Both cocrystals demonstrated physical stability upon storing at different relative humidity.

Thermodynamics of potassium diclofenac salt aqueous solutions at various temperatures

Enthalpies of solution and dilution of aqueous solutions of sodium diclofenac salt were measured by isoperibolic calorimeter at 293.15, 298.15, 303.15, 308.15 and 318.15 K. The concentration of the electrolyte was restricted to solubility salt at various temperatures and did not exceed 0.035–0.057 mol kg−1 values depending on the studied temperature. The virial coefficients were derived from Pitzer’s model and the excess thermodynamic functions of both the solution and the components of the solution were calculated. The analysis of thermodynamic characteristics of the solution from concentration and temperatures was carried out and discussed.

Polymorphs and solvates of felodipine: analysis of crystal structures and thermodynamic aspects of sublimation and solubility processes

Single crystals of the crystallosolvates [felodipine + N-methylformamide] and [Fel + DMF] with 1 : 1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. The crystal structures were analyzed together with the already published felodipine forms I and II, and crystallosolvate [Fel + formamide]. The temperature dependence of saturated vapor pressure for polymorphic form I was obtained and thermodynamic characteristics of sublimation process with crystal lattice energy estimation were calculated. The fusion processes of solvatomorphs were investigated and their thermophysical parameters were determined. The differences in crystal lattice energy of the three crystallosolvates and those of the unsolvated forms were obtained by solution calorimetry technique. The impact of the “guest”/solvent molecules on the crystal lattice energy of the crystallosolvates was analyzed. The dissolution kinetics of felodipine form I, [Fel + FA], [Fel + N-Me-FA] and [Fel + DMF] in water was investigated. The solution calorimetric and solubility experiments were used to obtain the thermodynamic characteristics of phase transitions (crystallosolvate → unsolvated phase).

Enthalpies of the dissolution and dilution of aqueous solutions of rubidium and cesium diclofenac at 293.15–318.15 K

Enthalpies of the dissolution and dilution of aqueous solutions of rubidium and cesium diclofenac (RbDC and CsDC) are measured at 293.15, 298.15, 308.15, and 318.15 K at concentrations of water of less than 0.1 mol/kg. The heat capacity of RbDC and CsDC crystal salts is determined. Changes in the thermodynamic properties of both a solution and its components vs. concentration and temperature is considered. An increase in the endothermicity of the dissolution of RbDC and CsDC with a rise in temperature is noted. It is shown that the dissolution of both RbDC and CsDC electrolytes in water is determined by the contribution from entropy. It is shown that in aqueous solutions of RbDC and CsDC, the degree of binding of water molecules is higher than in pure water at temperatures below 303.15 K.

Heat capacities of crystalline tetraalkylammonium salts

The behavior of crystalline tetraalkylammonium salts at 290–350 K was studied by differential scanning calorimetry. For tetraethyl- and tetrabutylammonium bromides (Et4NBr and Bu4NBr), the experimental heat capacities agreed well with the literature values. For tetrahexyl-, tetraheptyl-, and tetraoctylam-monium bromides (Hex4NBr, Hep4NBr, and Oct4NBr), phase transitions were found between crystal modifications whose characteristic temperatures depended significantly on the size of the cation. Empirical equations for the temperature dependences of the heat capacities of the salts within the ranges of homogeneous equilibrium phases were derived.

Dissolution enthalpy of phosphoric and acetic acids in water-dimethylformamide mixtures

Dissolution enthalpies of phosphoric and acetic acids were experimentally determined (concentration of acid, up to 3 mol/kg) in water—dimethylformamide (DMF) mixtures (molar part of DMF, from 0 to 1) at 298.15 K. Standard dissolution enthalpies of acids in the mixed water-DMF solvent were estimated on the basis of the obtained data.

A thermochemical study of aqueous solutions of sodium naproxene

The enthalpies of solution of sodium naproxene and dilution of its aqueous solutions were measured on an isoperibolic calorimeter at 293.15, 298.15, 303.15, 308.15, 313.15, and 318.15 K. The maximum content of the electrolyte was determined by its solubility at the given temperature (0.038–0.083 mol/kg solvent). The Pitzer model was used to obtain the virial coefficients for calculations of many excess thermodynamic properties of both solutions and their components. Changes in these characteristics depending on the concentration and temperature are considered.

Thermodynamic properties of LiCl solutions in N-methylacetamide at 308.15–328.15 K

Enthalpies of dissolution of crystalline LiCl and enthalpies of dilution of LiCl solutions in N-methylacetamide (NMA) with electrolyte concentrations no greater than 0.32m are measured on an isoperibolic calorimeter at 308.15, 318.15, and 328.5 K. Standard enthalpies of the dissolution of LiCl in NMA are calculated at different temperatures. The thermodynamic properties of the solution and its components are calculated and analyzed in the investigated range of concentrations and temperatures.