OMahony_2013_measuring.pdf (870.05 kB)
Measuring the solubility of a quickly transforming metastable polymorph of carbamazepine
journal contribution
posted on 2013-05-01, 14:08 authored by Marcus A. O'Mahony, Denise M. Croker, Åke C. Rasmuson, Stéphane Vesler, Benjamin K. HodnettThe solubility of the stable FIII polymorph of the pharmaceutical compound carbamazepine was measured by determining its solubility gravimetrically in ethanol and methanol. Where the metastable FI polymorph was suspended in a solution of ethanol, the stable FIII polymorph nucleated immediately initiating a solution mediated transformation from FI to FIII. This meant that the FI polymorph was not in thermodynamic equilibrium with the solution as FI was continually dissolving while FIII was growing. We show that the solubility of FI can be accurately measured by in situ microscopy using an adaption of the bracketing method and the results show that the solubility is close to but higher than the maximum solution concentration reached during the solution mediated transformation from FI to FIII carbamazepine in both solvents. The technique demonstrates a relatively simple and robust method for determining the solubility of a metastable crystalline phase which transforms quickly in solution.
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Organic Process Research & Development;17(3), pp. 512-518Publisher
American Chemical SocietyNote
peer-reviewedOther Funding information
SFIRights
This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Organic Process Research & Development 2012 © American Chemical Society after peer review. To access the final edited and published work see,http://dx.doi.org/10.1021/op300228gLanguage
EnglishExternal identifier
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