Acetylsalicylic acid
Analgesic
Measuring cell: TGA850
Pan: Aluminum 100 µl, with pierced lid
Sample preparation: As received, no preparation
TGA measurement: Heating from 25 °C to 300 °C at 1, 2, 5 and 10 K/min, all measurements are blank curve corrected
Atmosphere: Air, 50 cm3/min
The first diagram (28a) shows the effect of the heating rate on the decomposition of acetylsalicylic acid. The decomposition, that is the resulting weight loss, is shifted to higher temperature with increasing heating rates. The DTG curves, i.e. the first derivative of the TGA curves, are formed in order to calculate the percentage conversion curves that are used for further kinetic analysis. The DTG curves together with the choice of a suitable baseline allow the separation of the first decomposition step from further overlapping decomposition reactions (the TGA curves do not terminate horizontally).
The second diagram (28b) shows the complete evaluation using the model-free kinetics method. The conversion curves are calculated from the DTG curves using the baseline type ‘integral horizontal’. These conversion curves are, in turn, the basis for the model-free kinetics for the calculation of the activation energy. This lies in the range 100 – 140 kJ/mol and is a function of conversion, indicating a complex reaction. The activation energy allows a simulation of the decomposition reaction for other conditions (temperature and time). This is shown graphically and in tabular form in so-called iso-conversion plot and tables. In this presentation, the time required for the substance to reach a given percentage conversion (or in other words degree of decomposition) at a given temperature is evident.
The activation energy is determined as a function of the percentage conversion. The details are given in the diagrams.
Prediction of the storage time/storage temperature for a conversion of 1, 2, 3 or 4% (applied kinetics). It is evident from the table, that a conversion of 1% is reached when the substance is stored at 15.2 °C for 10,000 hours; 1 year has 8,760 hours.
Time | Conversion | |||
---|---|---|---|---|
1% | 2% | 3% | 4% | |
10000 h | 15.3 °C | 25.3 °C | 33.1 °C | 38.7 °C |
20000 h | 10.6 °C | 20.7 °C | 28.7 °C | 34.3 °C |
30000 h | 8.0 °C | 18.1 °C | 26.1 °C | 31.8 °C |
Please note: Extrapolation of results from reactions performed in the liquid state to the solid state have a high degree of uncertainty.
The example shows that thermal analysis and the application of model-free kinetics is an efficient means of estimating the potential storage lifetime of pharmaceutical preparations at a minimum expense. The TGA can of course only be used when the decomposition is coincidental with a significant weight loss.
It must be emphasized that this procedure can never replace a proper long-term test. The method is more useful for the preliminary selection of formulations. The formulations that exhibit good properties can then be subjected to the time-consuming and expensive final tests.
Kinetic Analysis of Decomposition, Acetylsalicylic Acid | Thermal Analysis Application No. HB820 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals