Solvent diversity in polymorph screening

Authors

  • Morten Allesø,

    1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
    Search for more papers by this author
  • Frans van den Berg,

    1. Department of Food Science, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark
    Search for more papers by this author
  • Claus Cornett,

    1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
    Search for more papers by this author
  • Flemming Steen Jørgensen,

    1. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
    Search for more papers by this author
  • Bent Halling-Sørensen,

    1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
    Search for more papers by this author
  • Heidi Lopez de Diego,

    1. Analytical R & D, H. Lundbeck A/S, Valby, Denmark
    Search for more papers by this author
  • Lars Hovgaard,

    1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
    Search for more papers by this author
  • Jaakko Aaltonen,

    1. Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
    Search for more papers by this author
  • Jukka Rantanen

    Corresponding author
    1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
    • Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Telephone: 45-35336000; Fax: 45-35336030.
    Search for more papers by this author

Abstract

Selecting a diverse set of solvents to be included in polymorph screening assignments can be a challenging task. As an aid to decision making, a database of 218 organic solvents with 24 property descriptors was explored and visualized using multivariate tools. The descriptors included, among others, log P, vapor pressure, hydrogen bond formation capabilities, polarity, number of π-bonds and descriptors derived from molecular interaction field calculations (e.g., size/shape parameters and hydrophilic/hydrophobic regions). The data matrix was initially analyzed using principal component analysis (PCA). Results from the PCA showed 57% cumulative variance being explained in the first two principal components (PCs), although relevant information was also found in the third, fourth and fifth component, revealing distinct clusters of solvents. Since five dimensions were not suitable for visual presentation, a nonlinear method, self-organizing maps (SOMs), was applied to the dataset. The constructed SOM displayed features of clusters observed in the first three PCs, however in a more compelling way. Thus, the SOM was chosen as the visually most convenient way to display the diversity of the 218 solvents. In addition, it was demonstrated how safety aspects can be considered by labeling a large fraction of the solvents in the SOM with toxicological information. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2145–2159, 2008

Ancillary