In the pharmaceutical field, knowledge of properties such as
- Thermal stability
concerning APIs (Active Pharmaceutical Ingredients) and excipients is important. They can be investigated by two thermoanalytical methods, as explained in the following.
1. Thermal stability
The standard ASTM E2550 defines the thermal stability of a material as the “temperature at which the material starts to decompose or react”. It specifies that the determination of this particular temperature takes place using a thermoanalytical method called thermogravimetry.
Please click here to see an example of the thermal stability determined on Aspirin®.
A medicine is usually not a single active ingredient but a mixture of the active ingredient with different excipients. In a tablet, for example, excipients are used to improve the appearance and taste of the final product to prevent the tablet from sticking to the punching tool, or to help dissolve it as soon as it is wet, etc.
Many excipients are pharmacologically inert. However, physical and chemical interactions between the active ingredient and excipients can affect the stability, safety and therapeutic efficacy of the drug. In this case, the term drug-excipient incompatibility is used. On the contrary, if the excipient does not affect the active ingredient, both substances are compatible.
First information about the compatibility of the active ingredient and excipient is obtained by means of:
You will find an example for a compatibility study with DSC and TGA here.
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 their physical properties such as:
This influences the processability of drug substances and the performance of drug products such as:
- Incorporation into the body
- Dissolution (rate)
For the same reasons, polymorphism also plays a role in food and cosmetics.
The different polymorphs can be characterized with differential scanning calorimetry (DSC).
Please click here to get more information about polymorphism.
Pseudo-polymorphism is a particular form of polymorphism where the different modifications result from an hydration or solvation.
In a solvate, the solvent molecules are entrapped in the crystalline structure of the substance. If this contains more than two solvents, it is referred to as a hetero-solvate.
In a hydrate, the solvent in association with the drug is water.
The characterization of solvates and hydrates is carried out mainly with thermogravimetry, possibly coupled with evolved gas analysis. A TGA measurement yields information about the amount of solvent/water present in a sample, and thus about the degree of solvation/hydration. Coupled evolved gas analysis allows for the identification of solvents released during heating.