Exploring the Formation of Multiple Layer Hydrates for a Complex Pharmaceutical Compound

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Abstract

The pharmaceutical compound A, 3-{2-oxo-3-[3-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)propyl]imidazolidin-1-yl}-3(S)-(6-methoxypyridin-3-yl)propionic acid, is known to exist in five different crystalline forms that differ in the hydration state ranging from the anhydrous desolvate over hemihydrate, dihydrate, and tetrahydrate forms to the pentahydrate. The formation of the higher hydrates and the concomitant lattice expansion leads to undesirable tablet cracking at higher humidities. In this work, particle-based simulation techniques are used to explore the hydrate formation of compound A as a function of humidity. It is found that a simulation strategy employing Monte Carlo simulations in the isobaric−isothermal and Gibbs ensembles and transferable force fields, which are not parametrized against any experimental data for compound A, is able to yield satisfactory crystal structures for the anhydrate and pentahydrate and to predict the existence of all five hydrates.

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This article has been cited by 2 ACS Journal articles (2 most recent appear below).

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  Generation of Zwitterionic Water Channels: Biszwitterionic Imidazolium Carboxylates as Hydrogen-Bonding Acceptors

  Shigeo Kohmoto, Shinpei Okuyama, Nobuyuki, Yokota, Masahiro Takahashi, Keiki Kishikawa, Hyuma Masu, and Isao Azumaya
  Crystal Growth & Design2011 Article ASAP

  • Generation of Zwitterionic Water Channels: Biszwitterionic Imidazolium Carboxylates as Hydrogen-Bonding Acceptors

    Shigeo Kohmoto, Shinpei Okuyama, Nobuyuki, Yokota, Masahiro Takahashi, Keiki Kishikawa, Hyuma Masu, and Isao Azumaya
    Crystal Growth & Design2011 Article ASAP

    Organic crystals containing several types of water channels are generated by clipping water molecules with biszwitterionic imidazolium carboxylates as hydrogen-bonding acceptors. The types of water channels to be generated depend on the size and the shape ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Simulations of Cracks Supported by Experiments: The Influence of the Film Height and Isotropy on the Geometry of Crack Patterns

  Johannes Richardi, Anh Tu Ngo, and Marie Paule Pileni
  The Journal of Physical Chemistry C2010 114 (41), 17324-17332

  • Simulations of Cracks Supported by Experiments: The Influence of the Film Height and Isotropy on the Geometry of Crack Patterns

    Johannes Richardi, Anh Tu Ngo, and Marie Paule Pileni
    The Journal of Physical Chemistry C2010 114 (41), 17324-17332

    Here, we show that cracks give valuable information on the height and the isotropy of nanocrystal films. Two-dimensional crack patterns are systematically studied by simulations and experiments varying the height and the anisotropy of the applied stress. ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links

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