Manufacturing of urea co-crystals by spiral gas–solid two-phase flow (S-GSF) based on spiral jet mills: a continuous, solvent-free, and scalable mechanochemical method

In this work, we report a spiral gas–solid two-phase flow (S-GSF) method based on spiral jet mills for the continuous mechanochemical preparation of urea co-crystals for the first time. Urea–adipic acid (UAA), urea–catechol (URCAT), urea–salicylic acid (USA) and urea–gypsum (URCASU) co-crystals were prepared to demonstrate the feasibility of this approach. The prepared products were characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The results showed that powdered products of the urea co-crystals can be obtained continuously by using this method without the addition of any solvent in the preparation process. Moreover, the UAA co-crystal prepared by S-GSF is in single polycrystalline form I, while form II, which appears in milling and ball milling, is not observed. The transcrystallization behavior among different polymorphs of the UAA co-crystal was studied and their thermodynamic stability was investigated by theoretical calculations. The results indicated that form I is a thermodynamically stable polymorph, and S-GSF is selective for the formation of form I. This phenomenon can be attributed to the fact that S-GSF provides strong mechanical action, as well as a low-temperature reaction environment, which distinguishes it from existing mechanochemical methods.