Abstract
Despite the rising interest in pharmaceutical cocrystals in the past decade, there is a lack of research on the solid processing of cocrystals downstream to crystallization. Mechanical stress induced by unit operations such as milling could affect the integrity of the material. The purpose of this study is to investigate the effect of milling on pharmaceutical cocrystals and to compare the performance of ball mill and jet mill, using caffeine–glutaric acid (1:1) cocrystal as the model compound. Our results show that ball milling induced polymorphic transformation from the stable Form II to the metastable Form I, whereas Form II remained intact after jet milling. Jet milling was found to be effective in reducing particle size, but ball milling was unable to reduce the particle size beyond a certain limit even with increasing milling intensity. The heating effect during ball milling was proposed as a possible explanation for the difference in the performance of the two types of mill. The local increase in t...
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