Thermal analytical methods such as differential scanning calorimetry (DSC) are important tools used in drug development to provide quantitative information about physical and chemical changes in materials as a function of temperature. DSC can be used to determine properties like melting points, glass transition temperatures, crystallization behavior, purity, and reaction kinetics. Samples are prepared in small pans and calibrated using standard reference materials before interpretation of transitions identified on DSC thermograms, which can indicate properties like polymorphism, purity according to established equations, or whether a compound is crystalline or amorphous. DSC finds regulatory use for characterization and is described in pharmacopeias with requirements for experimental documentation.

1. DSC: PRINCIPLE,
APPLICTION AND
INTERPRETATION
PRESENTED BY:
RAHUL KUMAR
M. PHARMA
BITS PILANI
RA JASTHAN

2. CONTENTS
Introduction
Types/ Modifications
Application
Sample Preparation
Calibration
Interpretation
References

3. INTRODUCTION
Thermal analytical methods have become important tools for the
development of modern medicines.
These instruments provide quantitative information about
exothermic, endothermic and heat capacity changes as a function
of temperature and time (such as melting, purity and glass
transition temperature).
Differential scanning calorimetry instruments are primarily used in
the earliest stages of drug development, where experiments are
often of an exploratory nature

4. TYPES OF TAHRMAL ANALYSIS
It includes – DTA, DSC
DSC is further categorized as :
Power-compensated DSC
Heat flux DSC

5. a)DTA b) PC DSC c) HF DSC

6. Application
•Glass transitions
•Melting and boiling points
•Crystallization time and temperature
•Percent crystallinity
•Heats of fusion and reactions
•Specific heat capacity
•Oxidative/thermal stability
•Rate and degree of cure
•Reaction kinetics
•Purity

7. Sample Preparation
DSC samples are analyzed in small metal pans, designed for optimal thermal conductivity and
minimum reaction with the samples (for example, aluminium alloy, platinum, stainless steel
and silver).
Pans may be open, pin-hole, covered or sealed

8. For accurate quantitative work the thermal mass of the sample and reference pans
should be matched.
Sample sizes of 3–5 mg, sometimes with less than 1 mg optimum result may be obtain

10. Calibration
To ensure expected working condition and accurate results.

11. Calibration Accessories
Micron Balance
Crucible sealing press
Crucible (2) : sample and reference 40 microliter
Calibration toolbox
Calibration material

13. Calibration Process

15. Calibration standards have classically been metals such as indium, tin, bismuth and
lead.
Separate calibration is required at each scan rate used

16. Interpretation: Exothermic Transition -Up

17. Endothermic Transition -Down
Differential scanning calorimetry scan of
sucrose (undried), showing the glass transition
temperature, (Tg), recrystallization exotherm
temperature (Tc) and enthalpy (DHc), melting
endotherm temperature (Tm) and enthalpy
(DHf) and onset of degradation 10K /min.
Endothermic transitions are down

18. Melting Point
Where To is onset temperature of
melting, Te is the extrapolated
onset melting temperature,
enthalpy of fusion (⌂Ho), Tm is
peak melting temperature

19. Purity
Ts = Te – RTe 2X
ΔHoF
Van’t Hoff eq.
A streight line relationship is expected
between Ts and 1/F for pure compound.
where Ts is the sample temperature at
equilibrium (K),
Te is the melting temperature of the pure
component (K),
R is the gas constant (8.314 J/mol/K),
X is the molar fraction of the impurity,
ΔHo is the enthalpy of fusion of the pure
compound (J/mol) and
F is the fraction of the sample molten at Ts.

20. Polymorphism

21. CRYSTALLINE OR AMORPHOUS
COMPOUND ?

22. Regulatory issues
The use of DSC for the determination of transition temperatures and sample purity is described
in the United States Pharmacopeia.
It is stated that detailed records should be kept of all experimental parameters, and that special
attention be given to the number of significant figures reported in the results.
The patent or regulatory status of newly discovered drug forms may depend on the quality of
the DSC maintenance and calibration records.

23. REFERENCES
1. Barnes, A.F., Hardy, M.J. and Lever,T.J. (1993) J.Therm.Anal. 40, 499–509
2. Ford, J.L. and Timmins, P. (1989) Pharmaceutical Thermal Analysis:Techniques and
Applications, Halsted Press, New York, NY, USA
3. Burroughs, P. (1980) Anal. Proc. (London) 17, 231–234
4. Richardson, M.J. (1997) Thermochim.Acta 300, 15–28
5. Turi, E.A., ed. (1997) Thermal Characterization of Polymeric Materials (2nd edn),
Academic Press, San Diego, CA, USA
6. Jones, K.J. et al. (1997) Thermochim.Acta 304/305, 187–199
7. Schawe, J.E.K. (1996) Thermochim.Acta 271, 127–140
8. Boller, A., Jin,Y. and Wunderlich, B. (1994) J.Therm.Anal. 42, 307–330

24. 9. Wunderlich, B. et al. (1998) Thermochim.Acta 324, 77–85
10. Craig, D.Q.M. and Royall, P.G. (1998) Pharm. Res. 15, 1152–1153
11. Hensel, A. and Schick, C. (1997) Thermochim.Acta 304/305, 229–237
12. Varma-Nair, M. and Wunderlich, B. (1996) J.Therm.Anal. 46, 879–892
13. Barker, A.D. (1993) J.Therm.Anal. 40, 799–805
14. Price, D.M. (1995) J.Therm.Anal. 45, 1285–1296
15. Tan, Z-C. and Sabbah, R. (1994) J.Therm.Anal. 41, 1577–1592