In this work, liquid
antisolvent precipitation of carbamazepine
(CBZ), an anticonvulsant and antiepileptic drug, was carried out from
its solutions in an ionic liquid (IL), [BMIM][Cl], using water as
an antisolvent. Precipitation was carried out in the presence of ultrasound
and additives such as hydroxyl propyl methyl cellulose (HPMC), bovine
serum albumin (BSA), and polyvinylpyrrolidone (PVP). In-situ Raman
spectroscopy was employed to uncover any polymorphic transformations
that might occur in the solution during precipitation. It was found
that the dihydrate (DH) form of CBZ precipitated from IL solution
irrespective of the additive or the mixing condition. However, characterization
of the freeze-dried CBZ powders obtained from liquid antisolvent (LAS)
precipitation revealed that the DH CBZ underwent dehydration and transformed
selectively to anhydrous Form III (P-monoclinic) and Form I (triclinic)
in the absence and presence of additives, respectively. The additives
were found to influence the final polymorphic outcome by “kinetically
entrapping” the metastable Form I during dehydration. The morphology
of CBZ particles obtained under all conditions was found to be long
needle-like where each individual needle appeared to have been formed
by aggregation of several smaller needles. Time-resolved scanning
electron microscopy studies show that the morphology of CBZ particles
is a result of a non-classical particle formation pathway followed
by secondary nucleation and growth.