The term polymorphism comes from the Greek, “poly” meaning “multiple” and “morph” meaning “form”. Used in different areas as programming or biology, it designates the ability of a variable, of an object, of a gene to take on multiple forms.
In the pharmaceutical industry, polymorphism refers to the ability of a material to exist in more than one crystal structure. The different polymorphic forms of a pharmaceutical substance are usually called α, β, … or I, II, … or A, B, …, where modification α/I/A is the most stable one. If the different crystal forms result from hydration or solvation, the term pseudo-polymorphism is used.
Polymorphism is very challenging because even though two polymorphic substances have the same chemical structure, they differ in their properties. Because a polymorphic substance can change its structure over time, unexpected changes in its bio-availability, physical properties, stability, etc., can occur during storage. For this reason, as well as concerning patent registration, it is crucial to be aware of, and knowledgeable about, the existence of all of the potential modifications of a polymorphic substance and the properties, stability, and quality of each.
How to be sure a substance is in the correct modification?
For that, you need a DSC.
Let us take the example of paracetamol. This active pharmaceutical ingredient (API) has three modifications:
- Modification I has a monoclinic crystal structure; it is the most stable one and melts at 169°C 
- Modification II has a orthorhombic crystal structure; it has better compression properties than form I and melts at 157°C 
- Modification III is unstable and thus difficult to characterize
Figure 1 displays the DSC measurement on paracetamol during two heatings to 200°C. Between both heatings, the sample was cooled at 10 K/min. During both heatings, a melting peak is detected, but not at the same temperature! This is to explain by the formation of a different modification during cooling. Before the first heating, paracetamol was in the monoclinic form; during cooling at 10 K/min, it crystallized into the orthorhombic form.
Other examples of the characterization of different modifications of a polymorphic substance are given in the NETZSCH Application Note 127.