Thermal method usage features for multicomponent crystal screening

In this work, the effectiveness of thermal methods, liquid-assisted grinding (LAG), and crystallization by a slow evaporation technique for the screening of multicomponent crystals of quinolones (nalidixic acid (NLD), oxolinic acid (OXL), norfloxacin (NFX), levofloxacin (LFX), and enrofloxacin (EFX)) with tyramine (TYA) was investigated. The screening confirmed the formation of eight new multicomponent crystals. The LAG method has the highest effectiveness with seven hits out of eight targets. Crystallization by a slow evaporation technique has a multicomponent crystal screening efficiency comparable to that of the DSC screening method (three hits out of eight targets). Single crystals for [LFX + TYA] (1 : 1) salt form I and for two solvated salts of quinolones ([NFX + TYA + MeOH] (1 : 1 : 1) and [EFX + TYA + H2O] (1 : 1 : 1)) were obtained by slow crystallization from solutions. Their crystal structures were solved by single-crystal X-ray diffraction. By using thermal screening methods only, it was possible to detect the polymorphic form of the salt [LFX + TYA] (1 : 1) form II, which was not formed when the experiment was carried out in the presence of a solvent. The mechanisms of desolvation of the obtained four salt solvates of quinolones were investigated.