Chemicals case study
Industry Sector
Pharmaceutical
Organizations
AstraZeneca Plc, UK
University of Manchester, School of
Chemical Engineering and Analytical
Sciences
Accelrys
Key Products
Materials Studio, Polymorph
Predictor, Reflex Plus, X-Cell,
COMPASS, Discover, and DMol
3
Page 1 of 3
Combining Targeted Screening and
Directed Crystallization Experiments
for Polymorphs of Diflunisal
Researchers at AstraZeneca Plc (UK), the University of Manchester School of
Chemical Engineering and Analytical Sciences, and Accelrys have explored a
novel approach for polymorph screening of diflunisal (a fluorinated aromatic
carboxylic acid used as non-steroidal anti-inflammatory drug) using a suite of
crystal structure prediction software combined with subsequent specifically
targeted experimental crystallization.
Using a process of predicting structures, identifying and analyzing hydrogen
bonding motifs, and applying the data to the rational design of crystallization
experiments, the researchers were able to yield significant numbers of new,
previously unsolved crystalline polymorphs of diflunisal from a limited experi-
mental screen. The combined software/experimentation process was validated
by its success. The ability to explore the molecular packing of potential poly-
morphs of an organic compound in silico can be of significant importance to
the biotechnical and pharmaceutical industries, helping to guide experiments
and hence save time and money.
Polymorphism is common in organic compounds, where, for example, variation
in the hydrogen bonding of functional groups can lead to a variety of possibili-
ties for molecular packing in the crystallized form. These polymorphic crystals
each have different physical and mechanical properties such as melting point
or solubility, and regulatory requirements exist for thorough exploration and
testing of possible polymorphs during the development of pharmaceutical
products.
Usually, this exploration is a long-drawn-out process and success is not guar-
anteed: traditional experimenta