Reverse Antisolvent Method To Avoid Jelly-like Phase Generation and Preparation of Crystalline Cefquinome

In the pharmaceutical industry, crystalline products are preferred because of their higher purity, chemical and physical stability, as well as tunability through crystal engineering. In this study, a crystalline cefquinome (CFQ) product was prepared for the first time. A reverse antisolvent crystallization (RAC) recipe was proposed to avoid the formation of a jelly-like phase (JLP) during the solution crystallization process. A comprehensive characterization and analysis were conducted for the undesirable JLP by using thermogravimetric analysis and rotational rheometry. The results show that the JLP is a semisolid fluid, and it hinders nucleation and growth of crystals. The formation of JLP should be considered as an important factor of lacking crystalline CFQ products in past decades. In this work, the ternary phase diagram was determined to study the mechanism of the RAC process and analyze it for further optimization. The optimized crystallization process was monitored and analyzed by powder X-ray diffraction, in situ Raman spectroscopy, and in situ focused beam reflectance measurement, and produced a higher crystallinity product. In addition, the solubility of the crystalline product and the commercial product was measured in three solvents. The results indicate a higher solubility of the crystalline CFQ product compared to the commercial product which shows great potential for further application.