PerkinElmer Life and Analytical Sciences
710 Bridgeport Avenue
Shelton, CT 06484-4794 USA
Didier Clnet Sanofi-Aventis
Analytical Sciences Department
Physical Characterization Laboratory
13, quai Jules Guesde
94403 Vitry-sur-Seine - FRANCE
Separation of transitions
Detection of weak transitions
HyperDSC (or High Speed DSC), a thermal technique that complements conventional calorimetry, has over the last few years found applications in the fields of pharmaceutical, polymers and compounds.
This technique features measurements taken at high heating (or cooling) rates, from 100 to 500 C/min. It is an approach that makes it easier to detect such events as glass transition or the melting of a compound when they are concealed by kinetic phenomena like, for example, water vaporization, crystallization or chemical degradation.
Furthermore, HyperDSC offers greatly enhanced analysis sensitivity due to the concentration of the energy phenomena measured into a very brief space of time. Calorimetric analyses on samples of very low mass (below 10 μg) are thus made possible. The detection limits permitted by this technique can be lowered considerably as compared with conventional DSC, down to values < 1% when quantifying physical forms (amorphous or crystalline). HyperDSC analyses can be carried out on the power compensation Diamond DSC from PerkinElmer shown in Figure 1.
Presentation and relevance of Hyper-DSC
First, a quick review of the differences between power compensation DSC and heat-flux DSC is presented. Its design and working principle makes power compensation DSC the best technique for analysis at high heating and cooling rates.
The small low-mass furnace (Figure 2) of the power compensation Diamond DSC is highly responsive with respect to the chosen temperature programs. Power compensation provides a direct measurement of the heat flow given off or absorbed by the sample, as well as constant temperature readings up to rates of 500 C/min.
A very short startup transient
As is shown in Figure 3, it takes the Diamond DSC less than 10 seconds to reach a selected temperature setting, even at a rate as high as 500 C/min. Thus, for an experiment beginning at -65 C and carried out at 200 C/min, the apparatus reaches equilibrium at about 30 C, the temperature from which any transition can be measured. By comparison, a classical heat-flux DSC can take 30 to 60 seconds and is not ready for the detection of a transition before +35 C or more likely +135 C, which therefore makes it necessary to start the analysis at a much lower temperature.
A direct, reliable measurement of heat flux up to 500C/min.
The melting peak of an Indium standard has reliable onset and enthalpy values at any chosen heating speed, even at 500 C/min as shown in Figure 4 and Table 1.
HyperDSC's enhanced sensitivity
Fast Scan DSC provides increased sensitivity with decreasing experiment time because the output of a DSC is mW or J/sec. Figure 5 depicts the increase in heat flow signal at higher heating rates.
The enthalpy measured remains the same independent on the scanning rate; only the intensity of the signal is reinforced because of the concentration of energy absorbed or released in a very short time frame.
Analysis of a polymorph mixture
The first sample show n is a mixture of Carbamezipine stable form I and metastable form III. Figure 6 shows an experiment carried out at 500 C/min in which a very weak endotherm was detected for the melting of Carbamazepine form III, a polymorph making up only 1% of the sample content.
Analysis of a weak glass transition (Tg)
The detection of a glass transition in an amorphous material is also improved by HyperDSC (Figure 7). With HyperDSC detection limits < 1% (w/w) can be reached in order to quantify the amorphous material in pharmaceutical compounds .
At such heating rates, thermal gradients within the sample can have an impact, widening the signals detected and superimposing thermal phenomena inside the material. One way to limit this thermal gradient is to perform analyses on samples of very small mass, less than a milligram .
Application of HyperDSC to several Sanofi-Aventis samples
This active ingredient comprises a mixture of physical forms (phases α + ).
A DSC measurement under standard conditions at 10 C/min causes form α to transform into form , which prevents the two crystalline forms from being quantified by comparing melting enthalpies.
In this case, HyperDSC inhibits phase transformation, and the melting endotherms of the two forms can thus be used to quantify the mixture. Figure 8 shows an experiment at 100 C/min, carried out on a reconstituted mixture of form α / form at 95 / 5%.
Transition separation by HyperDSC
Glass transition and evaporation
This amorphous active ingredient has a high water content (about 10%) whose evaporation conceals glass transition during a DSC analysis under conventional conditions (5 C/min). An experiment at 300 C/min pushes water evaporation up to high temperatures, making it possible to detect glass transition, as is shown in Figure 9. The decomposition of the compound is clearly identified after evaporation.
Melting and decomposition
Figure 10 shows the capability of HyperDSC to distinguish melting from the chemical decomposition of the molecule.
Similar for forms B and D, two polymorphs of another component, HyperDSC clearly separates the melting endotherms of each form from the decomposition exotherm of the active ingredient as shown in Figure 11. It should be noted that the melting temperatures and enthalpies for the two polymorphs are different while the decomposition profile is the same at higher temperature.
Enhanced sensitivity for a Lyophilisate
The analyzed lyophilisate is made up half of glycine and half of an active ingredient in amorphous form. Figure 12 shows how HyperDSC contributes to the detection of the glass transition, in comparison with conventional DSC.
HyperDSC is an excellent tool to enhance material characterization. It provides multiple benefits in the pharmaceutical analysis. As demonstrated HyperDSC increases the sensitivity of DSC analysis, separates transitions and allows better evaluation of polymorphic materials. The analysis time is very short and permits you to increase your sample throughput or to use this technique as a screening tool for new materials.
Discover new dimensions in Thermal Analysis with HyperDSC.
1 M. Hurtta, I. Pitknen, Thermochimica Acta 419 (2004) 19-29
2 Pijpers, Thijs F. J.; Mathot, Vincent B.F.; Goderis, Bart; Scherrenberg, Rolf L.; van der Vegte, Eric W. Macromolecules 2002, 35, 3601-3613