Thermal Analysis with Pharmaceutical Applications

Karen Griffin, Senior Analytical Chemist

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Introduction
Thermal analysis techniques, such as differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) are used to characterize the properties of a variety of materials, including polymers, ceramics, and pharmaceuticals. Test materials can be solids, semi-solids and liquids and the atmosphere can be nitrogen or air. The DSC provides a wide range of information on a test material by monitoring endothermic and/or exothermic events (e.g. glass transition (Tg), melting point (MP), decomposition) at either isothermal or dynamic temperature profile. The TGA is commonly used in conjunction with the DSC results. The TGA monitors weight of the test material over a temperature range or over time at a specific temperature.

Thermal Analysis 1

A sharp exothermic peak in a DSC thermogram may be attributed to crystallization or decomposition of the test material. For decomposition, the TGA thermogram would show a corresponding decrease in the weight of the test material over the equivalent. These techniques were used to study the effects of lyophilization on a test material, and as a measure of quality control, as will be discussed here. 

DSC analysis of Pelletized Lyophilized Suspension
A pelletized lyophilized pharmaceutical suspension was submitted for analysis by DSC. The goal of this work was to determine whether or not lyophilization resulted in thermodynamic changes in the drug product. The customer did not submit a non-lyophilized sample for comparison; that data was previously collected, and all comparison was completed by the customer. The DSC analysis was carried out using a TA Instruments Q100 differential scanning calorimeter equipped with a refrigerated cooling system. Sample material was weighed into an aluminum hermetic sample pan and a lid hermetically sealed on the pan and exposed to a programmed temperature profile. The purge gas was nitrogen and the data obtained were analyzed using the TA Instruments Universal Analysis program. A glass transition (Tg) was observed in both the 1st and 2nd heating scans of the sample as demonstrated in Figure 1 (page 2). The glass transition temperature at half-height for the sample was determined to be -59 °C in the 1st heating scan and -57 °C in the 2nd heating scan.

TGA & DSC Analyses of Pharmaceutical Test Material
A sample was submitted for analysis by both TGA and DSC to serve as a quality control check. The customer knew what the sample should be composed of and the TGA data was used to verify that the decomposition products were consistent with the expected material composition. The DSC data was used to follow the changes in Tg with repeated heating/cooling cycles.

The TGA analysis was performed using material in a platinum pan that was heated from room temperature to 800 °C in air purge. The data obtained were analyzed using the TA Instruments Universal Analysis program.

The sample exhibited multiple weight losses over the temperature range of the analysis under an air atmosphere, as shown in Figure 2 (page 3). A large-scale loss began at 286 °C and ended with no residue at 800 °C. Below 286 °C, the sample displayed broad loss, the first through 114 °C presumably being moisture. Loss ranges are summarized in Table I.

Thermal Analysis 2

Figure 1. DSC Thermogram of Lyophilized Suspension.


Thermal Analysis 3

The DSC analysis was performed using a TA Instruments Q100 differential scanning calorimeter equipped with a refrigerated cooling accessory. The purge gas was nitrogen and sample was weighed into an aluminum pan and a lid crim ped on top. The sample was subjected to a temperature profile and the data obtained was analyzed using the TA Instruments Universal Analysis program.

The test material displayed what appeared to be a Tg with significant enthalpic relaxation near room temperature on the first heating cycle but the transition was very weak on subsequent heating cycles, as shown in Figure 3 (page 4). There was an additional Tg near 125 °C observed on the subsequent two heating cycles. Results are summarized in Table II.


Thermal Analysis 4
Figure 2. TGA Thermogram of Test Material


Thermal Analysis 5