Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions

et al. 2022

Preprint

Self Cite

We present a crystallographic and computational study of three hydantoin-based active pharmaceutical ingredients nitrofurantoin, furazidin, and dantrolene aimed at identifying factors resulting in different propensities of these compounds to form polymorphs, hydrates, solvates, and solvate hydrates. This study is a continuation of our research towards understanding how small structural differences in closely related compounds affect their propensity to form different crystal phases, as all three compounds contain an imidazolidine-2,4-dione scaffold and a N-acyl hydrazone moiety and all form multiple crystalline phases. Crystallographic and computational analysis of the already known and newly obtained nitrofurantoin, furazidin and dantrolene crystal structures was performed by dissecting the properties of individual molecules and searching for the differences in tendency to form hydrogen bonding patterns and characteristic packing features. The propensity to form solvates was found to correlate with the relative packing efficiency of neat polymorphs and solvates and the ability of molecules to pack efficiently in several different ways. Additionally, the differences in propensity to form solvate-hydrates were attributed to the different stability of the hydrate phases.

mentioning

confidence: 89%

Section: Conformation and Conformational Energymentioning

confidence: 99%

Crystallographic and Computational Analysis of Solid Form Landscape of Three Structurally Related Imidazolidine-2,4-dione Active Pharmaceutical Ingredients: Nitrofurantoin, Furazidin and Dantrolene

Trimdale-Deksne

Kons

et al. 2022

Preprint

Self Cite

“…The obtained crystallographic data are given in Table 1 and more details are available in Table S1. Although crystal structures of FUR THF•H2O and FUR•DMF•H2O were published as part of our previous study of FUR degradation 33 , these structures are described and analysed here for the first time.…”

Section: Solvates Obtained In the Crystallization Experimentsmentioning

confidence: 99%

“…FUR is a nitrofurantoin analogue with an antibacterial activity 29 frequently used in the treatment of urinary tract infections mainly in eastern European countries. 30 Furazidin is known to exist in two polymorphs I and II [31][32] as well as two solvate hydrates: THF solvate hydrate (CSD refcode ASATIZ) and DMF solvate hydrate (ASATOF) 33 . In our performed crystallization experiments of FUR formation of several pure solvates and additional solvate hydrates was observed.…”

Section: Introductionmentioning

confidence: 99%

Crystallographic Study of Solvates and Solvate Hydrates of an Antibacterial Furazidin

Mishnev

Stepanovs

et al. 2022

Preprint

In this study we present a detailed crystallographic analysis of multiple solvates of an antibacterial furazidin. Solvate formation of furazidin was investigated by crystallizing it from pure solvents and solvent-water mixtures. Crystal structure analysis of the obtained solvates and computational calculations were used to identify the main factors leading to the intermolecular interactions present in the solvate crystal structures and resulting in formation of the observed solvates and solvate hydrates. Furazidin forms pure solvates and solvate hydrates with solvents having large hydrogen bond acceptor propensity and with a hydrogen bond donor and acceptor formic acid. In solvate hydrates the incorporation of water allows formation of additional hydrogen bonds and results in more efficient hydrogen bond network in which water is “hooking” the organic solvent molecule, and this slightly reduces the cut-off of solvent hydrogen bond acceptor propensity required for obtaining a solvate. The crystal structures of all pure solvates are formed from molecule layers and in almost all structures solvent is hydrogen bonded to the furazidin, but the packing in each solvate is unique. In contrast, the hydrogen bonding and packing in most solvate hydrates are nearly identical.

“…FUR is a nitrofurantoin analogue with an antibacterial activity 35 frequently used in the treatment of urinary tract infections mainly in eastern European countries. 36 Furazidin is known to exist in two polymorphs I and II [37][38] as well as two solvate hydrates: THF solvate hydrate (CSD refcode ASATIZ) and DMF solvate hydrate (ASATOF) 39 . In our performed crystallization experiments of FUR formation of several pure solvates as well as additional solvate hydrates were observed.…”

Section: Introductionmentioning

confidence: 99%

Crystallographic Study of Solvates and Solvate Hydrates of an Antibacterial Furazidin

Mishnev

Stepanovs

et al. 2022

Preprint

In this study we present a detailed crystallographic analysis of multiple solvates of an antibacterial furazidin. Solvate formation of furazidin was investigated by crystallizing it from pure solvents and solvent-water mixtures. Crystal structure analysis of the obtained solvates and computational calculations were used to rationalize the main factors leading to the intermolecular interactions present in the solvate crystal structures as well as resulting in formation of the observed solvates and solvate hydrates. Furazidin forms pure solvates and solvate hydrates with solvents having large hydrogen bond acceptor propensity as well as with a hydrogen bond donor and acceptor formic acid. In solvate hydrates the incorporation of water allows formation of additional hydrogen bonds and results in more efficient hydrogen bond network in which water is “hooking” the organic solvent molecule, and this slightly reduces the cut-off of solvent hydrogen bond acceptor propensity required for obtaining a solvate. The crystal structures of all pure solvates are formed from molecule layers and in almost all structures solvent is hydrogen bonded to the furazidin, but the packing in each solvate is unique. In contrast, the hydrogen bonding and packing in most solvate hydrates are nearly identical.