Abstract
In this study, treatment of anhydrous trazodone powder with ammonium carbamate in warm water crystallised two new polymorphs or dihydrates of trazodone after 5 h, whose structures were determined by X-ray single crystal diffraction. Each dihydrate contains infinite zigzag hydrogen-bonded chains of water molecules, which are stabilised by the N4 acceptor atom of the piperazine ring and the pendant carbonyl O1 atom of the triazole ring, as well as other water molecules. The strong dipole moment expected for the O1 atom makes it a good hydrogen bond acceptor for stabilising the chains of water molecules. Each molecule of trazodone has a similar conformation in both hydrates, except for the propyl chains, which adopt different conformations: anti-gauche in the β hydrate (triazole N-C-C-C and C-C-C-piperazine N) and anti-anti in the γ hydrate. Both piperazine rings adopt chair conformations, and the exocyclic N-C bonds are in equatorial orientations. The Hirshfeld surfaces and two-dimensional fingerprint plots for the polymorphs were calculated using CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms.
Highlights
IntroductionUbiquitous for the presence of life, can have important and sometimes adverse effects on the manufacture of drugs and their performance
CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms
Two new dihydrates of trazodone resulted from the same crystallisation reaction, and were characterised by single crystal X-ray structure determinations
Summary
Ubiquitous for the presence of life, can have important and sometimes adverse effects on the manufacture of drugs and their performance. It can be introduced through an active ingredient, excipients, or the atmosphere, and can increase interactions between a drug and its excipients, dissolve soluble components or induce phase transitions [1]. The hygroscopicity, a measure of the water vapour taken up by a solid, which might affect its surface and bulk properties, is an important criterion for deciding the solid-state form of the oral drug [11]. When a compound or a drug co-crystallises with water, a new crystalline phase, termed a hydrate, is formed.
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