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

b. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

Desorption behavior of 8 different solvents from α and β tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) has been studied in this work. Solvent desorption from samples stored at 95% and 50% relative solvent vapor pressure was studied in isothermal conditions at 30 C. The results of this study demonstrated that: solvent desorption rate did not differ significantly for both phases; solvent desorption in all cases occurred faster from samples with the largest particle size; and solvent desorption in most cases occurred in two steps. Structure differences and their surface properties were not of great importance on the solvent desorption rates because the main factor affecting desorption rate was sample particle size and sample morphology. Inspection of the structure packing showed that solvent desorption rate and amount of solvent adsorbed were mainly affected by surface molecule arrangement and ability to form short contacts between solvent molecule electron donor groups and freely accessible tegafur tetrahydrofuran group hydrogens, as well as between solvents molecule proton donor groups and fluorouracil ring carbonyl and fluoro groups. Solvent desorption rates of acetone, acetonitrile, ethyl acetate and tetrahydrofuran multilayers from α and β tegafur were approximately 30 times higher than those of solvent monolayers. Scanning electron micrographs showed that sample storage in solvent vapor atmosphere promotes small tegafur particles recrystallization to larger particles.

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

Desorption behavior of 8 different solvents from α and β tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) has been studied in this work. Solvent desorption from samples stored at 95% and 50% relative solvent vapor pressure was studied in isothermal conditions at 30 C. The results of this study demonstrated that: solvent desorption rate did not differ significantly for both phases; solvent desorption in all cases occurred faster from samples with the largest particle size; and solvent desorption in most cases occurred in two steps. Structure differences and their surface properties were not of great importance on the solvent desorption rates because the main factor affecting desorption rate was sample particle size and sample morphology. Inspection of the structure packing showed that solvent desorption rate and amount of solvent adsorbed were mainly affected by surface molecule arrangement and ability to form short contacts between solvent molecule electron donor groups and freely accessible tegafur tetrahydrofuran group hydrogens, as well as between solvents molecule proton donor groups and fluorouracil ring carbonyl and fluoro groups. Solvent desorption rates of acetone, acetonitrile, ethyl acetate and tetrahydrofuran multilayers from α and β tegafur were approximately 30 times higher than those of solvent monolayers. Scanning electron micrographs showed that sample storage in solvent vapor atmosphere promotes small tegafur particles recrystallization to larger particles.

a. Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow 119991, Russian Federation

b. A. N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky Prospect 31, Moscow 119071, Russian Federation

c. Department of Chemistry, University of Latvia, Kr. Valdemara Street 48, Riga LV-1013, Latvia

d. JSC Grindeks, Krustpils Street 53, Riga LV-1057, Latvia

e. JSC Pharmstandard, 141700 Likhachevsky Drive 5b, Dolgoprudny, Moscow Region 141700, Russian Federation

Afobazole {systematic name: 2-[2-(morpholin-4-yl)ethylsulfanyl]-1H- benzimidazole} is a new anxiolytic drug and Actins, Auzins and Petkune [(2012). Eur. Patent EP10163962] described four polymorphic modifications. In the present study, the crystal structures of two monoclinic polymorphs, 5-ethoxy-2-[2-(morpholin-4-ium-4-yl)ethylsulfanyl]-1H-benzimidazol-3-ium dichloride, C15H23N3O2S 2+·2Cl-, (II) and (IV), have been established from laboratory powder diffraction data. The crystal packing and conformation of the dications in (II) and (IV) are different. In (II), there are channels in the [001] direction, which offer atmospheric water molecules an easy way of penetrating into the crystal structure, thus explaining the higher hygroscopicity of (II) compared with (IV).

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

b. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

Kinetics of anhydrous cocrystal hydration and that of cocrystal monohydrate formation from starting compounds in the solid state are studied as a function of RH and time. The propensity of the anhydrate to hydration is related to the crystal structures of anhydrous and hydrated forms.

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

b. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

Reaction of isoniazid with benzoic acid, sebacic acid, suberic acid, and cinnamic acid results in formation of cocrystals. Two polymorphs of isoniazid-suberic acid and two polymorphs of isoniazid-cinnamic acid cocrystals were isolated. Crystal structure analysis shows the presence of a pyridine-carboxylic acid synthon in the studied cocrystals. The hydrazide group of isoniazid participates in N-H···O and N-H···N hydrogen bond formation, producing different supramolecular synthons. The stability study of isoniazid cocrystals has been performed over a 22 week period. A comparison of melting points of isoniazid-dicarboxylic acid 2:1 cocrystals shows the decrease of melting point with an increasing length of the acid. Solubility of isoniazid-carboxylic acid cocrystals tends to increase with increasing solubility of the acid.

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

Solvent effects on α tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) phase transition to β tegafur during grinding with solvent additive, as well as phase transition in samples exposed to 95% relative solvent vapor pressure has been studied in this research. Samples containing 0.5% and 0.1% of β tegafur in α and β tegafur mixture, as well as samples of pure α tegafur were ground with different solvent additives, and conversion degrees depending on the solvent were determined using PXRD method. Samples with α and β tegafur weight fraction of 1:1 were exposed to 95% relative solvent vapor pressure, and phase transition rates were determined. Solubility of α tegafur, solvent sorption and desorption behavior on α and β tegafur have been examined. It was found that the conversion degree of α tegafur to β tegafur mainly depends on solubility of α tegafur in the relevant solvent, and the conversion degree to β tegafur is higher in such solvents, where solubility of α tegafur is higher. The samples ground in a ball mill with solvent additive had a trend of phase transition dynamics from α tegafur to β tegafur similar to the samples exposed to 95% relative solvent vapor pressure.