Chow, P. S.; Lau, G.; Ng, W. K.; Vangala, V. R., Stability of pharmaceutical cocrystal during milling : a case study of 1:1 caffeine-glutaric acid. Crystal Growth & Design 2017, 17 (8), 4064-4071.
Abstract:
Despite the rising interest in pharmaceutical cocrystals, there is a lack of research on the solid processing of cocrystals downstream to crystallization. The purpose of this study is to investigate the effect of milling on dimorphic caffeine−glutaric acid cocrystal using ball/jet mill. It reveals that ball milling induced polymorphic transformation from stable Form II to metastable Form I, whereas Form II remained intact after jet milling. Additionally, jet milling was found to be more effective in reducing particle size compared to ball milling. The difference in the performance of the two types of mill was attributed to the localized heating effect during ball milling and Joule-Thompson countering cooling effect during jet milling.
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Funding Info:
This work was supported by Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore.