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Development of a solvent free continuous co-crystallisation technique for carbamazepine-saccharin.Joshi, Onkar D. January 2012 (has links)
Co-crystals are emerging as a potential area in the field of crystal designing as it
improves material's physicochemical properties. Many groups are working on the
development of newer techniques for the preparation of co-crystals, which can be scalable
and contribute to the green agenda. Being continuous and scalable technique, our own
developed twin screw extrusion mediated solvent free continuous co-crystallisation (SFCC)
technique has been used for the preparation of carbamazepine: saccharin co-crystal.
Carbamazepine has been used as a model drug since it shows challenges such as low
solubility (BCS class II), polymorphism and thermolabile nature whilst, saccharin was used
as a co-former.
Effect of extrusion processing parameters such as shear, temperature and screw speed on cocrystallisation
has been studied. In addition to this, effect of particle size of co-crystal
components, use of hydrated form of carbamazepine, addition of solvent and application of
reverse elements on the purity of co-crystal was understood. Use of carbamazepine dihydrate
as a starting component yields pure co-crystals. The addition of small amount of polar solvent
in anhydrous carbamazepine also yields pure co-crystals whereas particle size did not show
any significant effect. Result showed that selection of processing temperature near to eutectic,
moderate shear and increase in residence time of component mixture in mixing zone was
mainly responsible for co-crystallisation. The extrudates were mainly characterised by
XRPD, DSC and in-vitro dissolution tests. Pure co-crystals prepared by addition of highly
Development of a solvent free continuous co-crystallisation technique for carbamazepine-saccharin ii
polar solvent have been showed drug release identical to that of pure co-crystals prepared by
solvent crystallisation.
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