Solution cocrystallization, an effective tool to explore the variety of cocrystal systems: caffeine/dicarboxylic acid cocrystals

Abstract

Although cocrystals have undergone a recent boost in popularity, limited time is spent on exploring the variety of possible cocrystal phases, which is likely due to the popularity and success of grinding methods. The number of studies where cocrystallization is systematically applied in solution remains limited. In this contribution, we present a rapid method for cocrystal synthesis in solution, which not only provides single crystals suitable for X-ray diffraction structural analysis but also allows one to explore the variety of cocrystal systems (polymorphs and solvates). Applying this approach to caffeine/dicarboxylic acid systems, we discovered 7 cocrystals and solved the structures for 6 of them. Astonishingly, the caffeine/mesaconic acid cocrystal system not only seems to be stoichiometrically diverse but furthermore also shows no less than 4 polymorphs of the 2 : 1 cocrystal.

Perbaikan Kelarutan Albendazol Melalui Pembentukan Kristal Multikomponen dengan Asam Malat

“…MAL diketahui mampu membentuk garam dengan efedrin (Wu et al, 2012) dan baklofen (Córdova-villanueva et al, 2018). Selain dapat membentuk garam, MAL juga diketahui dapat membentuk ko-kristal dengan sulfametoksazol (Imchalee & Charoenchaitrakool, 2015), kafein (Leyssens et al, 2014), prazikuantel (Cugovčan et al, 2017), dan temozolomid (Babu et al, 2012).…”

Predicting the Effect of pH on Stability and Solubility of Polymorphs, Hydrates, and Cocrystals

“…For a given system of API, CF, and solvent (here water) this phase diagram depicts the concentration range in which the desired CC is formed, as already earlier illustrated for systems exhibiting dissociation and salt formation 16 and for systems including polymorphic transitions and hydrate formation 18 . However, polymorphism 19,20 , as well as formation of salts and hydrates impede in turn the reliable and accurate measurement of these phase diagrams, resulting in a high experimental effort 10,[12][13][14][15] .…”

“…At industrial scale, the favored method for CC formation is the crystallization from solution [10][11][12][13] . In aqueous solutions, however, the CC formation is commonly interfered by pH-dependent dissociation as well as by salt formation of API and CF.…”

Influence of isomerism on recrystallization and cocrystallization induced by CO2 as an antisolvent

“…CO 2 has for long demonstrated its ability at micronizing organic compounds, but its capability at modifying the crystal lattice is more marginally investigated. [22][23][24] Although interactions are necessary to envisage cocrystal formation, they are insufficient to ensure a successful cocrystallization so various methods are to be investigated such as crystallization from solutions [25][26][27] , grinding or melting solids 28 . [19][20][21] A cocrystal is a molecular arrangement at solid state of two different molecules packed in periodic order through non-covalent bonds like hydrogen bonds, ion pairing, van der Waals forces, hydrophobic interactions, etc.…”