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Issue 20, 2014
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Investigating the dissolution of the metastable triclinic polymorph of carbamazepine using in situ microscopy

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Abstract

Despite a tendency to undergo solution-mediated polymorphic transformation, the dissolution behaviour of the metastable FI (triclinic) polymorph of the pharmaceutical compound carbamazepine (CBZ) was investigated using in situ optical microscopy. Experiments were performed at an undersaturation where single crystals of the metastable FI polymorph dissolved. Dissolution in different solvents was investigated at a constant undersaturation. Separately the sublimation of FI was examined and additionally the dissolution was observed at undersaturations where the more stable FIII polymorph crystallized. The results show that both the dissolution and sublimation of FI occur primarily in the direction of the a-axis of the FI crystal structure where the CBZ molecules are found to stack in this direction. The order for the dissolution rate of FI was acetonitrile ≥ methanol > ethanol. The order of the dissolution rates in each of the solvents is inversely correlated to the viscosity and the binding energy of the solvents with the (100) surface of FI in each of the solvents. This suggests that the rate determining step for the dissolution may be either the diffusion or the detachment of CBZ molecules from the surface of FI. A notable difference in dissolution behaviour is also observed at undersaturations where the more stable FIII polymorph nucleates and grows.

Graphical abstract: Investigating the dissolution of the metastable triclinic polymorph of carbamazepine using in situ microscopy

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Supplementary files

Article information


Submitted
09 Jan 2014
Accepted
26 Mar 2014
First published
26 Mar 2014

CrystEngComm, 2014,16, 4133-4141
Article type
Paper
Author version available

Investigating the dissolution of the metastable triclinic polymorph of carbamazepine using in situ microscopy

M. O'Mahony, C. C. Seaton, D. M. Croker, S. Veesler, Å. C. Rasmuson and B. K. Hodnett, CrystEngComm, 2014, 16, 4133
DOI: 10.1039/C4CE00062E

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