a. Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, Poznań, Poland

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

High pressure strongly favors the highest-density polymorph Z of active pharmaceutical ingredient 2-(2,6-xylidino)-5,6-dihydro-4H-1,3-thiazine hydrochloride (xylazine hydrochloride, XylHCl) up to about 0.1 GPa only, but still higher pressure destabilizes this structure. Above 0.1 GPa, XylHCl preferentially crystallizes as solvates with CH2Cl2, CHCl3, or (CH3)2CHOH depending on the solvent used. However, when XylHCl·H2O is dissolved in any of these solvents, the high-pressure crystallizations yield the hydrate XylHCl·H2O only. The single crystals of the CH2Cl2, CHCl3, and (CH3)2CHOH solvates could be grown in situ in a diamond anvil cell, which allowed their structure determination from the single-crystal diffraction data. At 0.4 GPa the XylHCl·H2O hydrate undergoes a pressure-induced phase transition doubling the unit cell dimensions.

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

b. Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN, United States

Degradation of drug furazidin was studied under different conditions of environmental pH (11–13) and temperature (30–60 °C). The novel approach of hybrid hard- and soft-multivariate curve resolution-alternating least squares (HS-MCR-ALS) method was applied to UV–vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The system was found to be comprised of three main species and best characterized by two consecutive first-order reactions. Furazidin degradation rate was found to be highly dependent on the applied environmental conditions, showing more prominent differences between both degradation steps towards higher pH and temperature. Complimentary qualitative analysis of the degradation process was carried out using HPLC-DAD-TOF-MS. Based on the obtained chromatographic and mass spectrometric results, as well as additional computational analysis of the species (theoretical UV–vis spectra calculations utilizing TD-DFT methodology), the operating degradation mechanism was proposed to include formation of a 5-hydroxyfuran derivative, followed by complete hydrolysis of furazidin hydantoin ring.

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

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

A series of dasatinib crystalline forms were obtained, and a hierarchical cluster analysis of their powder X-ray diffraction patterns was performed. The resulting dendrogram implies 3 structural groups. The crystal structures of several solvates representing 2 of these groups were determined. The crystal structure analysis confirms the isostructurality of solvates within structural group I and suggests a correlation between solvent molecule size and trends in crystal structures within this group. In addition, the formation relationships in 2-solvent media between different dasatinib solvate groups were determined. The formation preference of solvates was found to follow the ranking group I > group III > group II.

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

Cocrystallisation with a series of related compounds allows for the exploration of trends and limitations set by structural differences between these compounds. In this work, we investigate how the length of a dicarboxylic acid influences the outcome of cocrystallisation with isoniazid. We have performed a systematic study on the mechanochemical, thermal and solvent vapour-assisted cocrystallisation of aliphatic dicarboxylic acids (C3-C10) with isoniazid. Our results demonstrate that the rate of mechanochemical and vapour-assisted cocrystallisation depends on the acid chain length and shows alternation between odd- and even-chain acids. The results of thermal cocrystallisation showed that the eutectic melting temperatures of isoniazid-dicarboxylic acid mixtures follow the same trend as the melting points of dicarboxylic acids.

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

A detailed study of molecular conformation and intermolecular interactions in the experimental crystal structures and general trends observed in the Cambridge Structural Database as well as theoretical calculations were performed to identify the reason for the formation of different crystal structures of two chemically very similar pharmaceutical molecules benperidol and droperidol. The most important difference between both molecules was the weak intermolecular interactions formed by the central ring which therefore was responsible for the formation of different crystal structures. Cross-seeding experiments were performed to check the possibility for the formation of mutually isostructural phases, and theoretical calculations were performed to compare the stability of experimentally observed phases and theoretical isostructural phases by therefore rationalizing the results of the cross-seeding experiments. In cross-seeding crystallizations, three new droperidol phases—an ethanol monosolvate, a dihydrate and a new polymorph, all three isostructural to already known phases of benperidol—were obtained.