Issue link: https://www.e-digitaleditions.com/i/988595
34 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m Lyophilization can be correlated to the peak of the derivative. As seen in the example, the derivative value begins to increase, reaches a maximum, then abruptly decreases, indicating first weight loss is complete at 150 °C, the second at 500 °C, and the third at 750 °C. The TGA method requires only small quantities, as little as 2 mg of material (2). When evaluating a TGA scan, adsorbed water can be distinguished from absorbed water, which can be distinguished from the water of hyd rat ion. In conju nct ion with high-temperature differen- tial scanning calorimetry (HT- DSC), TGA can distinguish water evolved during degradation (6). This method, however, will mea- sure bot h surface and bound water in addition to all volatiles. Therefore, just like LOD, the type of water present, absorbed or ad- sorbed, must be distinguished. Most of ten, t he sur face ad- sorbed water will be vaporized at a lower temperature and earlier time. Absorbed water, required to first diffuse to the sample sur- face then vaporize, is ref lected in a more gradual weight loss at higher temperatures and over a longer time. If a hydrate is present, a sudden weight loss at a distinct temperature can be observed as the crystal hydrate melts. Figure 3 illustrates a gradual weight loss from surface adsorbed water over a temperature range of 40 °C to 65 °C. Note the change in the rate of weight loss beginning at 67 °C ref lected in the weight percent and derivative weight (%/°C). Two approaches to testing are commonly used for TGA: dynamic and isothermal. In dynamic testing, the temperature is increased at a constant, linear rate. A typical heating rate is 10 °C per min- ute. In the isothermal method, the temperature is kept constant for the duration of the test, and the Figure 2: Example of a thermogram. Figure 3: Example of a gradual weight loss thermogram.