Ionic co-crystals of racetams: solid-state properties enhancement of neutral active pharmaceutical ingredients via addition of Mg2+ and Ca2+ chlorides

Abstract

Mechanochemical and solution based reactions of solid brivaracetam (BRV) and seletracetam (SEL), antiepileptic drugs from UCB's pipeline, with the inorganic salts MgCl₂ and CaCl₂, yield ionic co-crystals with changed or improved physico-chemical properties with respect to pure drugs (melting point, hygroscopicity, crystal morphology). All co-crystals are characterized via a combination of solid-state techniques, i.e. single crystal and powder X-ray diffraction, variable temperature X-ray diffraction, DSC, TGA and hot-stage microscopy (HSM).