Additive effects on the solvent-mediated anhydrate/hydrate phase transformation in a mixed solvent

Haiyan Qu*, Marjatta Louhi-Kultanen, Juha Kallas

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Citations (Scopus)


Additives are one of the most influential factors that can affect the polymorphism and solvation state and the morphology of the crystals during crystallization. In this work, the effects of five different additives, sodium lauryl sulfate (SLS), polyethylene glycol 6000 (PEG), hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), D-mannitol, on the phase transition from anhydrous (CBZA) to dihydrate (CBZH) carbamazepine in an ethanol-water mixture containing 61 mol % ethanol were studied. A Raman in-line probe was used to obtain the real time transformation rate during the transformation. The mechanism of the additive effects on the phase transition was studied by investigating the influence of the additives on the solubility of CBZA and CBZH and on the cooling crystallization of CBZH. It was observed that HPMC exhibited a strong inhibiting effect on the phase transformation at both 15 and 10°C. Furthermore, it was found that HPMC selectively increased the solubility of CBZH but had no effect on the CBZA solubility. As a consequence, the solubility difference of CBZA and CBZH decreased dramatically. This resulted in a reduced supersaturation level during the phase transformation. SLS showed a slight promotion effect on the nucleation and crystal growth of CBZH by decreasing the metastable zone width and increasing the size of the final CBZH crystals. The additives had an insignificant effect on the viscosity of the solvent.

Original languageEnglish
Pages (from-to)724-729
Number of pages6
JournalCrystal Growth and Design
Issue number4
Publication statusPublished - Apr 2007
MoE publication typeA1 Journal article-refereed

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