Hydrate Stability, Theophylline

Sample

Theophylline monohydrate, various samples

Theophylline anhydrous form

Application

Active ingredient

Conditions

Measuring cells: TGA850

Pan: Aluminum 100 µl, with pierced lid

Sample preparation: As received, no preparation

TGA measurement: Heating from 30 °C to 300 °C at 20 K/min, blank curve corrected

Atmosphere: Nitrogen, 80 cm³/min

Interpretation

Storage of the theophylline monohydrate without special protection leads to loss of the water of crystallization because it is unstable under normal conditions of humidity. The TGA curves show this residual water as a step. It can be seen that during storage reference sample 2 has lost almost half of its water of crystallization and that reference sample 1 has lost it completely. The substance should therefore be stored, tightly sealed, in a well-filled container. Since such reference substances are used as standards or reference samples for other methods, it is important to determine the actual content of the active substance before performing any calculations. An increasing weight loss occurs at temperatures above 150 °C because the vanillin evaporates and decomposes.

Evaluation

The weight loss is determined from the TGA curve. The evaluation is performed using horizontal steps. The value expected stoichiometrically for the monohydrate is 9.1%.

The evaluation of the SDTA curves shows the endothermic loss of water of crystallization from the monohydrate (reference sample 3) as well as the melting point of the anhydrous form at about 269.6 °C.

Conclusion

Thermogravimetric analysis is the method of choice for the rapid quantification of water of crystallization, especially since the technique requires only small amounts of sample.

Hydrate Stability, Theophylline | Thermal Analysis Application No. HB811 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals