A Comparative Study of the Ionic Cocrystals NaX (α-d-Glucose)₂ (X = Cl, Br, I)

Abstract

The mechanochemical formation of the ionic cocrystals of glucose (Glc) and sodium salts Glc 2 NaCl•H 2 O (1) and Glc 2 NaX (X = Br (2), I (3)) is presented. Products are formed by co-milling Glc with three sodium salts (NaCl, NaBr, NaI). The ionic cocrystals were obtained under both neat grinding and liquid-assisted grinding conditions, the later found to accelerate the reaction kinetics. The crystal structures of the ionic cocrystals ( 2) and (3) were solved from powder X-ray diffraction data. The structure solution contrasts with the structure of Glc 2 NaCl•H 2 O (1) where the electron density at three halide crystallographic sites is modeled as of being the intermediate between water molecule and a chloride ion. The reaction pathways of the three ionic cocrystals were investigated in real time using our tandem approach comprising a combination of in situ synchrotron powder X-ray diffraction and Raman spectroscopy. The results indicate the rapid formation of each cocrystal directly from their respective starting materials without any intermediate moiety formation. The products were further characterized by DTA-TG and elemental analysis.

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

“…Differently, single-step LAG of PZQ in water results in the hemihydrate when the reactant is PZQ Form B, possibly related to the structural similarity between the two forms, as better addressed below. The present findings add to the recent studies involving real-time in situ grinding experiments, which show that mechanochemical reactions may present different mechanistic steps and intermediates [49][50][51].…”

Mechanochemical Preparation and Solid-State Characterization of 1:1 and 2:1 Ionic Cocrystals of Cyanuric Acid with Alkali Halides

“…For all the other ICCs, therefore, structures had to be determined from X-ray powder diffraction data, which revealed, inter alia, that most ICCs discussed here are anhydrous. The formation of anhydrous compounds of alkali salts is per se rather unusual, since the majority of ICCs of alkali halides prepared this far ,, tends to form hydrates, while anhydrous forms can be only obtained, in some cases, by subsequent dehydration processes, and are, in general, highly hygroscopic. We attribute this difference to the peculiar structure of CA, i.e., to its small size and highly symmetrical shape, a combination that affords optimal packings with spherical ions, as will be apparent in the following.…”

“…Therefore, to elucidate the crystal structure of the mechanically prepared cocrystals, one can either attempt recrystallization from solution or structure determination directly from powder data. In the former case, however, as mentioned above, the difference in solubility of the components in a given solvent must be taken into account, as dissolution of the cocrystal often implies separation of the components with very different solubility profiles. − This is especially true in the case of ionic cocrystals (ICCs), composed of an organic moiety and of inorganic salts or complexes, where the difference in solubility in water or organic solvents is usually very large. In all these cases, the best option to determine the nature of the ICC is the structure determination directly from X-ray powder diffraction (XRPD) data.…”

Chiral Resolution of RS-Oxiracetam upon Cocrystallization with Pharmaceutically Acceptable Inorganic Salts

“…Cocrystals in general, and ionic cocrystals (ICCs) in particular, have become attractive research topics in the pharmaceutical industry, since they can provide an alternative route to new pharmaceutical formulations compared to conventional salts. − A virtually infinite choice of molecular and/or ionic building blocks makes the number of possible combinations between active pharmaceutical ingredients (APIs) and ancillary coformers or other APIs limitless. ICCs belong to a class of multicomponent crystalline solids composed of neutral organic molecules and salts in a defined stoichiometric ratio. − Pharmaceutical ICCs are of particular interest, since they can modulate the physicochemical and biological properties of the APIs (e.g., bioavailability, solubility, intrinsic dissolution rate, morphology, stability toward humidity, and thermostability) in an impressive manner. − The formulation of drugs as cocrystals can be especially important with APIs that lack ionizable moieties, which therefore cannot be formulated and used as conventional salts. Enantiopure and racemic oxiracetam (see Scheme ) investigated in this work belong to such APIs.…”