Fast Loss on Drying Results through Thermogravimetric Analysis

Learn here how to quickly determine the water content of magnesium stearate, one of the most widely used pharmaceutical excipients.

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Loss on drying is a common method to determine the amount of volatile matter inside a chemical substance, e.g., a pharmaceutical. For quality control, the recommended conditions are specified in the corresponding monographs of the respective pharmacopoeias.

The standard method described is quite time-consuming and requires a high sample mass: 1 to 2 grams of the test material are put inside a flask and placed in a drying chamber at the temperature and for the time period given in the monograph. The instruction “dry to constant weight” means that the sample should be dried until two successive weighing operations (one hour apart, weighing after cooling the sample back to room temperature) show a difference of less than 0.5 mg per gram of substance [1].

However, testing can also be much faster – if thermogravimetric analysis is applied.

In the non-harmonized text of the Japanese Pharmacopeia (JP), it is stated that thermogravimetry is an alternative method for loss on drying experiments. Moreover, even USP <731> (Physical Tests/Loss on Drying) points out that in some individual monographs, TGA is required for that purpose.

Magnesium Stearate as an Example

For magnesium stearate, one of the most widely used excipients for solid dosage forms, drying at 105°C to a constant weight is mandatory [2]. 

The following measurements (displayed in Fig. 1 and 2) were carried out using a commercial magnesium stearate type of pharmaceutical grade as received. Fig. 1 illustrates a simulation of the standard loss on drying method by heating the sample to 105 °C at 20 K/min and then holding this temperature constant for a certain time. The complete mass-loss yield is 4.09%. This result could be achieved in only about 10 minutes.

Figure 1:             Simulation of a loss on drying test on magnesium stearate; displayed are the mass-loss curve (blue solid line) and the temperature curve (red dotted line) vs. time; sample mass: 6.7 mg, heating rate: 20 K/min, open Al crucibles, dynamic N2  atmosphere

As Fig. 1 reveals that most of the mass loss is taking place already in the heating section, a second experiment was performed in which a comparable amount of sample material was heated to 180°C at 20 K/min in a dynamic segment (Fig. 2). A result of 4.04 % mass loss can be observed. This experiment was finished in approx. 8 minutes only.

Figure 2:             Heating magnesium stearate to 180 °C at 20 K/min; displayed is the mass-loss curve (green solid line) vs. temperature; sample mass: 6.3 mg, heating rate: 20 K/min, open Al crucibles, dynamic N2 atmosphere

Both results fit well with the value of 4.02% given on the analysis certificate of the commercial magnesium stearate. The measurements themselves, however, could be finished very fast. The factor is approx. 6 compared to conventional loss on drying experiments. This makes thermogravimetric analysis an extremely useful tool for characterizing APIs (active pharmaceutical ingredients) and excipients. 

Reference:

[1]        USP 40, chapter <731>

[2]        Monograph text about Magnesium Stearate in USP, Stage 6 Harmonization, Official August 1, 2016    

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