cg8b01175_si_001.pdf (172.71 kB)
Reverse Antisolvent Method To Avoid Jelly-like Phase Generation and Preparation of Crystalline Cefquinome
journal contribution
posted on 2019-01-30, 00:00 authored by Liping Wang, Ting Zhang, Zhenguo Gao, Ying Bao, Qiuxiang Yin, Ping Na, Hongxun HaoIn
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.
History
Usage metrics
Categories
Keywords
thermogravimetric analysisJelly-like Phase Generationternary phase diagramoptimized crystallization processresults showbeam reflectance measurementRAC processCrystalline CefquinomeAntisolvent MethodCFQ productsRaman spectroscopyjelly-like phasepowder X-ray diffractionantisolvent crystallizationcrystal engineeringJLPCFQ productcrystallinity productsemisolid fluidsolution crystallization process