Good Stability Versus Good Tabletability: The Choice of Modification

Many pharmaceutical solids exhibit polymorphism, i.e., the ability of a substance to exist in different crystalline forms. The polymorphic form can have significant influence on pharmaceutical processing and can, for example, affect grinding, granulation and tabletability. A DSC measurement allows for the characterization of the present modification. Here, different modifications of paracetamol are distinguished by means of DSC.

Paracetamol, which is used for the treatment of pain and fever, is a polymorph, i.e., it exists in different crystalline forms called I, II and III. Each of these modifications behaves differently, particularly with regard to thermodynamic stability and compression ability. This last property influences the tabletability of paracetamol, i.e., its capacity to be transformed into a tablet under the effect of pressure.

How to Determine the Modification of Paracetamol?

For that, you only need a DSC. Weigh approx. 2 mg paracetamol in an aluminum crucible and start heating from room temperature to 200°C at a heating rate of 10 K/min. You will get one of the two curves displayed in figure 1. The peak indicates melting of the sample. In the green curve, the sample melts at 169°C. This melting temperature is typical for form I of paracetamol. It is the most frequently used modification because it is the most stable one. The melting peak is detected at 157°C in the blue curve. This means that this modification of paracetamol is form II and can be used for direct compression.
Figure 1. DSC measurement on paracetamol
Figure 1. DSC measurement on paracetamol
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