Exploring pharmaceutical ionic cocrystals of chiral racetams : from discovery to crystallization

Cocrystals in general, and ionic cocrystals (ICCs) in particular, have gained popularity in the pharmaceutical industry due to their striking advantages. To promote the application of ICCs, this thesis focuses on understanding the thermodynamics of ICCs, with a particular focus on chiral APIs. We investigated the crystallization thermodynamics and developed a robust upscalable crystallization process of an ICC system, which were up to now not yet explored. Moreover, we discovered some novel ICCs showing enhanced thermal stability. Furthermore, we discovered the homochiral preference around Ca and Mg cations with octahedral coordination and the conglomerate formation between etiracetam and zinc chloride, which will promote the application of ICCs in chiral resolution. In addition, the thermodynamics of an ICC system involving chiral species were investigated through quaternary phase diagram. At last, we designed a ternary ionic cocrystals (TICCs) strategy to cocrystallize two drugs without direct connecting sites with the TICCs showing enhanced thermal stability.(SC - Sciences) -- UCL, 202