Real Time Monitoring of Crystal Habit Changes during a Slurry Conversion

It is of crucial importance to the pharmaceutical industry to control the polymorphic crystallization and formation of solvates.  Often polymorphic transformation or hydration can be observed empirically through monitoring habit changes of crystals.
The need to study and control these transformations has led to the development of a small scale parallel crystallizer with particle visualization capabilities in combination with programmable temperature control and transmission analytics. 
The use of visual information and particle size statistics, on amillilitre scale, to monitor transformation processes which are accompanied by changes in crystal habit, is illustrated.


Carbamazepine(CBZ) is an anticonvulsant used to treat epilepsy and trigeminal neuralgia.  It has been extensively used as a model compound formany polymorphism and co-crystal formation studies. Anhydrous CBZ rapidly transforms to the dihydrate, when slurriedin water.  During this conversion the crystal habit of CBZ changes, from the block-like anhydrous crystals to long needles of the dihydrate.
Commercially available anhydrous CBZ was pre-ground using a mortar and pestle.  The pre-ground CBZ was added to water at 35°C.  The slurry of CBZ in water was monitored, using an on-board camera.  The hydration process of CBZ could be studied, following the change in particle size distribution, with time.

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