a p p l i c at i o n N o t e
Thermal Analysis
Author
Kevin Menard
PerkinElmer, Inc.
Shelton, CT USA
Measurement of the
Enthalpy of the Overshoot
at the Tg of Lyophilized
Formulation
Figure 1. DSC 8500
Figure 2. A standard run on a lyophilized sample of sucrose and PVP shows a
clear overshoot at the Tg on the first heat.
When running lyophilized formulations in the DSC, it
is not uncommon to see an overshoot or hump at the
Tg. This is often called the enthalpic overshoot and
is related to both the relaxation time of the material
and the material’s storage behavior. The PerkinElmer
Diamond DSC (Figure 1) and its Pyris software offer
two options for measurement of this overshoot.
A standard DSC run of a lyophilized formulation is
shown in Figure 2. The sample (5.2 milligrams of
lyophilized sucrose and polyvinylpyrolidone (PVP)) was
run in a hermetically sealed aluminum pan at 20 ˚C/
minute under nitrogen purge using an Intercooler II
for cooling. The glass transition, Tg, shows a definite
overshoot. Traditionally, one would also measure the
Tg on the second heating and then subtract that curve
from the initial heating curve to obtain the amount of
overshoot. This is often a less than optimal solution as
the Tg often shifts slightly to higher temperature on
the second heating.
A better approach is shown in Figure 3, where the same
material is run the same way, but the data from the first
heating curve are analyzed using the sigmoidal baseline
feature of the Pyris software. This gives a clear measurement of the overshoot on the first pass and does not require
subtraction of the data from a second heating. The Tg itself
can then be measured by either the standard method or by
fictive temperature (Tf) calculation as shown below.
Figure 3. Calculation of the overshoot and the Tg.
A second approach is to use StepScan, a modulated technique
provided as an option in the Pyris software, to separate the
enthalpic overshoot, a kinetic event, from the thermodynamic
event of the glass transition. The advantage of this method
is that both values are measured separately in one run.
However, these runs take longer than a standard run. Figure 4
shows the results of a StepScan run on 4.8 milligram of
the Sucrose-PVP formulation used above. The sample was
heated at 5 ˚C/minute in 2 degree steps and then held for
30 seconds. After data processing, the thermodynamic
Cp curve shows the Tg while the IsoK baseline shows the
enthalpic overshoot. The advantage of this method is that
Tg’s that show indentations or dimples (negative enthalpy)
can be analyzed as easily as those with positive enthalpic
overshoots (humps or peaks). See Figure 5.
Figure 5. A standard DSC run on a Sucrose-BSA formulation showing
negative enthalpy at the Tg. The easiest way to analyze this data is StepScan.
Conclusion
The PerkinElmer Diamond DSC offers several methods of
calculating the overshoot of the Tg, exploiting the inherent
advantages of the power compensated design.
Figure 4. StepScan on the Sucrose-PVP formulation used above.
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