About polymorphy and crystallinity

A crystalline structure is a unique arrangement of atoms or molecules in a crystalline solid. The crystalline structure plays a large role for the physical properties of the compound such as melting point, solubility, stability, dissolution etc.  Different crystalline structures are usually described as polymorphs.

A crystal structure is composed of a pattern, a set of atoms/molecules arranged in a particular way, and a lattice exhibiting long-range order and symmetry. Patterns are located upon the “points of a lattice”, which is an array of points repeating periodically in three dimensions. The points can be thought of as forming identical tiny boxes, called unit cells, that fill the space of the lattice. The lengths of the edges of a unit cell and the angles between them are called the lattice parameters. In contrast to a crystal, an amorphous “structure” is defined as a lack of a long range pattern – in an amorphous material the molecules are randomly oriented.

In the figure below some of the different possibilities of forming “crystalline structures”/polymorphs are illustrated by matchstick men representing molecules. From this very simple illustration it is easy to imagine that many possibilities of different crystalline structures might exist – and that not all structures are equally stable. Read more about how to crystallize new structures .

A crystal’s structure and symmetry play a role in determining many of its physical properties. A crystal has a well defined melting point and solubility which differs from other crystalline structures of the same material. In regard to a pharmaceutical compound a well defined and stable crystalline structure is usually desirable:

Almost all molecules have different opportunities for arranging in a crystalline network, i.e. forming polymorphic forms. One of these polymorphic forms will, at the given temperature, be more stable than the others. According to the laws of thermodynamics, a risk of spontaneous transformation from a metastable structure into a more stable one exist. Thus, it is of great importance to find the most stable crystalline structure to minimize this risk of transformation.

However, a higher stability is always coincident with a lower solubility. To increase the solubility of a compound, it is sometimes chosen to develop a metastable – or even amorphous form (amorphous material – as illustrated in the figure below).  Under these circumstances it should be examined under which conditions a transformation can be avoided (for a period – eventually the compound will transform, but it might take years).