Determination of the Specific Heat of Dry Substances of Moist Samples Using ADSC

Introduction 

Samples analyzed by Differential Scanning Calorimetry (DSC) often contain residual moisture (or, in general, solvent residues). In a conventional DSC experiment, the measurement curve then exhibits a broad endothermic evaporation peak. Such peaks often overlap other thermal processes, making the evaluation more difficult. In addition, solvent residues can influence other thermal effects. For example, residual moisture can act as a plasticizer and shift the glass transition of a sample to lower temperature. One way to separate the evaporation of residual moisture from other overlapping thermal effects is to use temperature modulated DSC

In ADSC, the linear temperature program is overlaid with a sinusoidal temperature modulation. This results in a sinusoidal heat flow. The analysis of such modulated heat flow curves allows overlapping effects to be separated. In this article, a possible procedure for the analysis of a pharmaceutical substance containing residual moisture is described as an example.

Experimental Details

The experiments were performed using a DSC822e equipped with an IntraCooler. The temperature program used was as follows: underlying heating rate of 1 K/min, temperature amplitude of 0.5 K, period of 48 seconds. The sample was a spray-dried mixture of two incompatible amorphous pharmaceutical substances with a residual moisture content of about 8%. The samples were measured in hermetically sealed crucibles self-generated atmosphere, and in open crucibles. The self-generated atmosphere was obtained by piercing a 50 µm hole in the aluminum lid of a sealed crucible

Figure 1 shows the three DSC curves measured in the usual way at 10 K/min. In the open crucible (curve c), a broad evaporation peak can be observed in the range 10 °C to 120 °C whose total enthalpy is about 1214 mJ (the measurement in the sealed crucible (curve a) was used as the baseline). Measurements with a TGA/SDTA851e showed a weight loss of 8.4% between room temperature and 150 °C (see Fig. 2). If the sample weight for the DSC experiment in the open crucible (5.652 mg) is taken into account, then a value of 2557 J/g is obtained for the weight-normalized heat of vaporization, which agrees well with the heat of vaporization of water (2400 J/g). From this we conclude that the water liberated was only weakly bound to the substrate. The weight loss can therefore be interpreted as being due to the evaporation of adsorbed water.

If the sample is measured in a hermetically sealed crucible, curve a is obtained. The marked deflection in the curve above 140 °C is caused by the rapid release of water vapor, which occurs when the crucible lid ruptures as a result of pressure build-up inside the crucible. The interpretation of the two endothermic peaks at about 50 °C and 130 °C is not so obvious. In a self-generated atmosphere (curve b), the evaporation process shifts toward the boiling point. Here again, a small endothermic peak can be seen at 50 °C just like in the curve obtained from the hermetically sealed crucible. In the open crucible, this peak shifts to a somewhat higher temperature. Since the moisture content is somewhat lower in an open crucible than in the sealed crucible or in a self-generated atmosphere (due to the evaporation process), we conclude that the moisture content directly influences the position of the effect. Figure 3 summarizes the results of the temperature-modulated experiments. The “total heat flow” curves correspond to the conventional DSC curves. Once again, measurements were performed in open crucibles (curves a and d) and in a self-generated atmosphere (curves b and c).

^{Determination of the specific heat of the dry substance of moist samples using modulated DSC (ADSC) | Thermal Analysis Application No. UC 142 | Application published in METTLER TOLEDO Thermal Analysis UserCom 14}