a. Faculty of Chemistry, University of Latvia, Jelgavas 1, Riga 1004, Latvia

b. JSC Grindeks, Krustpils 53, Riga 1057, Latvia

The thermodynamic stability of detomidine hydrochloride monohydrate has been evaluated on the basis of phase transition kinetics in solid state. A method free of empirical models was used for the treatment of kinetic data, and compared to several known solid state kinetic data processing methods. Phase transitions were monitored by powder X-ray diffraction (PXRD) and thermal analysis. Full PXRD profiles were used for determining the phase content instead of single reflex intensity measurements, in order to minimize the influence of particle texture. We compared the applicability of isothermal and nonisothermal methods to our investigation of detomidine hydrochlorine monohydrate dehydration.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

Objectives The main objective of this work was to develop a suitable analytical technique for determining trace amounts of the thermodynamically stable solid form in bulk samples of metastable form, to a sensitivity of 0.005%-1.0%. Tegafur (5-fluoro-1-(tetrahydro-2-furyl)-uracil) α and β crystalline forms were used as a model for this problem. Methods The trace content of the thermodynamically stable β polymorphic form in tegafur samples was increased by promoting phase transition from the bulk of thermodynamically metastable α form to β form, and achieving sufficient β form content for a quantitative powder X-ray diffractometry (PXRD) analysis. The phase transition was stimulated by adding water to the samples and then grinding in controlled conditions (temperature, time, grinding speed). A calibration line was constructed using the least squares method. Key findings By using a solvent that does not form hydrates with the analysed polymorphs, it was possible to promote the phase transformation from metastable form to the thermodynamically stable form. After sample preparation, the thermodynamically stable solid form content in the analysed mixture had increased proportionally to the initial weight fraction (0.005%-1.0%) of the stable form seed crystals in the samples, and the coefficient of proportionality was 43.0 ± 0.9, with a standard deviation S n = 1.5%. Conclusions A simple, sensitive, semi-quantitative analytical method was developed for the low-level determination of the thermodynamically stable polymorphic form in mixtures of thermodynamically stable and metastable polymorphs.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

b. Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, Helsinki 00014, Finland

Supramolecular complexes of phenanthridine have been prepared with various dicarboxylic acids. Cocrystallization of phenanthridine with fumaric acid, succinic acid, and isophthalic acid produced neutral cocrystals. Proton transfer from maleic acid and oxalic acid to the phenanthridine moiety results in salts of these two acids. It was found that neutral cocrystals are formed when the ΔpKa value of the complex is smaller than 2.56, whereas salts are formed when ΔpKa is greater than 3.66. The crystal structures of supramolecular complexes have been determined. The structure of each compound depends on acid geometry, and the compounds may be described as dimers, trimers, or chains. A comparison of the melting points, hydrogen bonds, and densities of each molecular complex and the corresponding dicarboxylic acid is presented. Utilizing the approximate relative bond strengths of hydrogen bonds, a comparison of the number of hydrogen bonds in the acid and the cocrystal is possible.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

Flecainide acetate forms acetic acid solvates with 0.5 and 2 acetic acid molecules. Powder X-ray diffraction, differential thermal analysis/thermogravimetric, infrared, and potentiometric titration were used to determine the composition of solvates. Flecainide acetate hemisolvate with acetic acid decomposes to form a new crystalline form of flecainide acetate. This form is less stable than the already known polymorphic form at all temperatures, and it is formed due to kinetic reasons. Both flecainide acetate nonsolvated and flecainide acetate hemisolvate forms crystallize in monoclinic crystals, but flecainide triacetate forms triclinic crystals. Solvate formation was not observed when flecainide base was treated with formic acid, propanoic acid, and butanoic acid. Only nonsolvated flecainide salts were obtained in these experiments.