Characterization of dihydrates prepared from carbamazepine polymorphs

Authors

  • Laura E. Mcmahon,

    1. Postgraduate Studies in Pharmaceutical Technology, The School of Pharmacy, University of Bradford, Bradford, W. Yorkshire BD7 1DP, U.K.
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  • Peter Timmins,

    Corresponding author
    1. International Development Laboratories, Bristol-Myers Squibb Pharmaceutical Research Institute, Reeds Lane, Moreton, Merseyside L46 1QW, U.K.
    • International Development Laboratories, Bristol-Myers Squibb Pharmaceutical Research Institute, Reeds Lane, Moreton, Merseyside L46 1QW, U.K.
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  • Adrian C. Williams,

    1. Postgraduate Studies in Pharmaceutical Technology, The School of Pharmacy, University of Bradford, Bradford, W. Yorkshire BD7 1DP, U.K.
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  • Peter York

    1. Postgraduate Studies in Pharmaceutical Technology, The School of Pharmacy, University of Bradford, Bradford, W. Yorkshire BD7 1DP, U.K.
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Abstract

To clarify earlier literature suggesting its existence in more than one solid form, carbamazepine dihydrate was prepared from individual anhydrous carbamazepine polymorphs I and III. The resultant materials were characterized by thermal and spectroscopic techniques, including variable-temperature Fourier transform (FT) Raman spectroscopy. On thermal dehydration, the carbamazepine dihydrates formed different anhydrous polymorphs depending on both starting material and dehydration conditions. Under conditions where liberated hydrate water cannot readily escape from around the sample, the dihydrate originating from polymorph III reverted to polymorph III, but under conditions of lower humidity/moisture, this dihydrate reverted to polymorph I. The dihydrate originating from polymorph I reverted to polymorph I irrespective of dehydration conditions. These observations could be due to a trace amount of nonhydrated original polymorph existing in the dihydrate phase that acts as a seed to regenerate the original polymorph under conditions where liberated hydrate water cannot readily escape from around the sample during dehydration. No evidence was generated that supported the existence of true polymorphs of carbamazepine dihydrate.

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