Theophylline monohydrate, various samples
Theophylline anhydrous form
Active ingredient
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
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.
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.
Monohydrate | Step, % | Evaluation range, °C | Sample weight, mg |
Reference 1 (old) | <0.1 | 32 to 120 | 11.988 |
Reference 2 (old) | 4.2 | 32 to 120 | 11.452 |
Reference 3 (new) | 8.7 | 32 to 120 | 5.287 |
Anhydrous form | <0.1 | 32 to 120 | 10.01 |
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