Polymorphism

Polymorphism is the ability of a solid material to form different crystalline structures (synonyms:  forms, modifications).

Although different modifications of a polymorph have the same chemical structure, they differ in the physical properties such as:

• Solubility
• Melting point
• Hygroscopicity
• Density
• Specific Heat capacity

This influences the processability of drug substances and the performance of drug products, such as:

• Stability
• Absorption into the body
• Dissolution (rate)
• Bioavailability

That is why polymorphism is an important topic for the pharmaceutical and also the food field.

The different modifications of a polymorph can be characterized with differential scanning calorimetry (DSC).

The figure depicts the two heatings of a paracetamol sample (initial mass: 2.6 mg). The heating rates as well as the cooling rate of the segment between both heatings amount to 10 K/min.

In the first heating, a peak at 169°C (onset temperature) is detected. This melting temperature is typical for the monoclinic form I of paracetamol. [1]

During cooling at 10 K/min, no crystallization occurs. Crystallization takes place during the second heating at 72°C (onset temperature) to form another modification with melting point at 157°C. This is typical for the orthorhombic form II of paracetamol [1].

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DSC