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A model polymorphic co-crystallization process for caffeine-glutaric acid from acetonitrile was monitored and controlled using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and particle vision measurement (PVM). A new method to calculate supersaturation for co-crystallization systems was proposed and used in this study. Results showed that feedback control of supersaturation was effective in eliminating the nucleation of the metastable Form I of co-crystal and also produced the largest particles with the lowest proportion of fines.
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Yu et al. (2011) studied this question.
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