Polymorphism of Cocrystals: The Promiscuous Behavior of Agomelatine

Abstract

It has been traditionally suggested that polymorphism of cocrystals is a phenomenon seen less frequently than in monocomponent crystals. However, since the research on cocrystals has recently experienced a big growth, the number of solved structures of polymorphic cocrystals in the Cambridge Structural Database has increased, which can help to understand better whether a lower impact of this phenomenon exists or not in multicomponent crystals. In this paper we describe the cocrystal landscape of agomelatine, a particularly promiscuous drug able to cocrystallize with up to nine different coformers. Interestingly, two of those coformers have produced polymorphic cocrystals during the screening, which converts agomelatine into a new example that questions the traditional belief of the lesser impact of polymorphism in cocrystals and highlights the importance of polymorphism studies in cocrystal screening. Our work is completed with the determination of the crystal structures of the new forms from combined single crystal/ laboratory X-ray powder diffraction data.

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…A more challenging aspect is to quantify nanocrystals in an amorphous material. Scherrer broadening (broadening of the diffraction peaks due to a reduction in crystallite size) may reduce the diffracted intensity for a crystalline material such that it becomes [205] √ (ATR) √ √ √ Nitrofurantoin cocrystal solvate, hydrates, salts [206] √ √ √ √ √ Nitrofurantoin cocrystal hydrate [126] √ √ √ √ √ Caffeine cocrystal polymorph, hydrate and solvates [116] √ [207] √ √ √ √ Salicylic acid cocrystal polymorphs [118] √ √ Felodipine cocrystal polymorph [115] √ √ √ Benzoic acid cocrystal polymorph [208] √ √ √ Glycine cocrystal polymorph [166] √ √ Vanillic acid cocrystal hydrate [125] √ √ √ √ Agomelatin cocrystal polymorph [209] √ √ √ √ Diclofenac cocrystal polymorph hydrate [104] √ √ (VT) √ √ Nicotinamide cocrystal polymorph [210] √ √ √ √ √ Phenazine cocrystal polymorph and solvate [105] √…”

Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance

“…Nuclear magnetic resonance ( 1 H-NMR) spectra were obtained on a Bruker 400 MHz instrument using DMSO-d 6 as solvent and TMS as an internal standard. Thermogravimetric analysis (TG) was carried out in a TA corporation Q500 equipment with the heating rate of 10 • C/min under a nitrogen gas purge with a flow of 60 mL/min.…”

“…In recent years, some solvates (Jevtana ® , Cabazitaxel Acetone; Makinist ® , Trametinib Dimethyl Sulfoxide) and salt hydrates (Tenelia ® , Teneligliptin Hydrobromide Hydrate; Acofide ® , Acotiamide Hydrochloride Hydrate) have been approved by the Federal Drug Administration (FDA) to market, which encourages pharmacologists and chemists to seek for new pharmacologically acceptable salt formation or solvates. Since multicomponent crystallization screening has begun to be routinely performed, solvates or hydrates of salt formation have been a subject of keen interest in order to control polymorphic formation and to explore the formation mechanism [6][7][8][9][10].…”

“…be routinely performed, solvates or hydrates of salt formation have been a subject of keen interest in order to control polymorphic formation and to explore the formation mechanism [6][7][8][9][10].…”

Agomelatine–hydroquinone (1:1) cocrystal: novel polymorphs and their thermodynamic relationship

“…Because AGO has poor water solubility, diverse solid forms of AGO have been investigated to increase its solubility (Zheng et al, 2011;Zhang et al, 2016;Du et al, 2013;Skořepová et al, 2016;Yan et al, 2012;Lee et al, 2018). Among the reported cocrystals, AGO-hydroquinone (AGO-HYQ, see Scheme 1) cocrystal has been reported to exist in two polymorphic forms [forms (I) and (II)] and it was suggested that the two polymorphs are monotropic with the higher melting form (II) being the stable form at room temperature (297 K) (Prohens et al, 2016). With our interest in structural and thermodynamic aspects of cocrystal polymorphs (Aitipamula et al, 2014), we have revisited the polymorphism in AGO-HYQ cocrystal and found two novel polymorphs [forms (III) and (IV)].…”