Chem. Sci. http://dx.doi.org/10.1039/c1sc00430a (2011)

Credit: © 2011 RSC

Polymorphism — the existence of different crystal structures of the same compound — is a problem in the pharmaceutical industry, because different polymorphs of the same drug may have different physical properties. Monitoring these subtle differences at each stage of a rigorous production process is a huge expense. Obtaining high-quality crystal structures is not always possible or practical in these circumstances.

Now, Sunil Varughese and colleagues from the Indian Institute of Science and the University of Southern Denmark have used a nanoindentation technique, which can measure the mechanical properties of very small amounts of solids to extremely high precision, to study and differentiate between the different polymorphs of aspirin. Aspirin, although used and studied as a drug for more than a century, has only recently been revealed to have a metastable polymorphic form, known as form II. The structures of the two polymorphs are very similar in two dimensions, and form II has been observed to transform into the more stable form I at ambient conditions.

The different physical properties of the polymorphs — such as elastic modulus and hardness — mean that nanoindentation can be used to differentiate between them, as form II is considerably softer than form I. Varughese and colleagues discovered that what had appeared to be single crystals of form II in fact contained small domains of form I — something that single-crystal diffraction had failed to detect.