Differential Scanning Calorimetry (DSC)

Differential Scanning Calorimetry (DSC)

DSC is suitable to examine all physical processes taking place during heating and cooling of a pharmaceutical compound, for example, melting point, stability of the compound, decomposition temperature etc. Determination of the thermal behaviour is a required part of the physical characterisation of a pharmaceutical compound.

Differential scanning calorimetry is highly relevant to:

  1. Determine melting point, desolvation, glass transition, heat capacity, sublimation or thermal decomposition point of your compound, for instance, as an ID method. 
  2. Examine the stability of the compound, as transitions or melting at low temperature is not desirable.
  3. Evaluate the relative stability of different crystalline forms to study transitions between states.
  4. Find out if the polymorphic forms are monotropic or enantiotropic.
  5. Evaluate crystallisation behaviour during heating – which might, for instance, lead to new polymorphic forms.
  6. Comparison of batches. Differences in energies upon melting might be due to amorphous material impurities or content, i.e. for evaluation of batch-to-batch variation.
  7. Purity evaluation by freezing point depression and applied for intermediates, raw materials, and final drug substances.
  8. Quantify and qualify the presence of the small amount of amorphous phase in a crystalline sample.
  9. Study stability of amorphous drug substances.
  10. Predict stability/instability of amorphous solid dispersions.
  11. Screen for co-crystals and polymorphs.
  12. Study phase diagram. Describe the type of enantiomer/stereoisomer/diastereomer mixture – compound or racemate. 
  13. Study drug-excipient compatibility.
  14. Study oxidative stability by determining the oxidative-induction time (OIT) or oxidation-onset-temperature (OOT) of a sample and other chemical reactions.
  15. Perform safety screening—the presence of an exothermic event to assess the stability of a substance to heat.
  16. Study of retardation of the glass transition temperature as a function of relative humidity to predict the stability of amorphous materials and amorphous solid dispersion.
  17. Search for the best polymer for amorphous solid dispersion.
  18. The thermodynamics analysis of proteins can reveal necessary information about the global structure of proteins and protein/ligand interaction. 

Instrument and measuring principle DSC

Measure the temperatures and heat flow associated with transitions in materials as a function of time and temperature in a controlled atmosphere.

A small amount of sample is needed. Differential scanning calorimetry measures the amount of energy (heat) absorbed or released when a specimen is heated, cooled, or held at a constant temperature. 

The instrument applied by Particle Analytical is a Mettler DSC 823e Differential Scanning Calorimeter (DSC).

InstrumentTA DSC2500 modulated DSC
USP/Ph. Eur.USP 891/Ph. Eur 2.2.34 Thermal Analysis
Temperatures-65 to 700 °C
Heating rateUp to 20 °C/min
Sample amount5-10 mg

Consult our Experts


Dr. Changyong Lu
QC Chemist

Dr. Anna Shevchenko
Principal Scientist


Chiu MH, Prenner EJ (2011) Differential scanning calorimetry: An invaluable tool for a detailed thermodynamic characterisation of macromolecules and their interactions. J Pharm Bioallied Sci. 3(1):39-59.

Desai S, Shaikh M, Dharwadkar S (2003) Preformulation compatibility studies of etamsylate and fluconazole drugs with lactose by DSC. J Therm Anal. 71(2): 651-658.

O’Neill M J (1964) The Analysis of a Temperature-Controlled Scanning Calorimeter. Anal Chem 36(7): 1238–1245.

Pungor E, Horvai G, (2020) In A Practical Guide to Instrumental Analysis, CRC Press (15): 184-187.

Schön A, Brown RK, Hutchins BM, Freire E (2013) Ligand binding analysis and screening by chemical denaturation shift. Anal Biochem  443(1):52-57. 

Verdonck E, Schaap K, Thomas LC (1999) A discussion of the principles and applications of Modulated Temperature DSC (MTDSC). Int J Pharm 192(1):3-20.

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