DSC --PRINCIPLE, DSC CURVE, ADVANTAGES, DISADVANTAGE AND APPLICATION

1. Presenter:
Amruta Balekundri
M.Pharm 1st semester,
Department of Pharmaceutical
Quality Assurance,
KLE College of Pharmacy,
Belagavi.
1

2. Contents:
• Introduction Thermal Analysis
• Differential scanning calorimetry
• History of DSC
• Principle of DSC
• Typical DSC curve
• Instrumentation
• Calibration
• Advantages
• Disadvantages
• Application
2

3. Thermal analysis:
• Thermal analysis refers to any technique for the study of
materials which involves thermal control.
• Measurements are usually made with increasing temperature,
but isothermal measurements or measurements made with
decreasing temperatures are also possible.
3

4. Thermal analysis:
• In fact, any measuring technique can be made into a thermal
analysis technique by adding thermal control. Simultaneous
use of multiple techniques increases the power of thermal
analysis, and modern instrumentation has permitted extensive
growth of application.
• The basic theories of thermal analysis (equilibrium
thermodynamics, irreversible thermodynamics and kinetics)
are well developed
4

5. Types of Thermal analysis:
5

6. Common Thermal Analysis Methods and the
Properties Measured:
6

7. Differential scanning calorimetry:
7

8. History of DSC
 The technique was developed by E. S. Watson and M. J.
O'Neill in 1962 , introduced commercially in 1963
at Pittsburgh Conference on Analytical Chemistry and Applied
Spectroscopy.
 First Adiabetic differential scanning calorimeter that could be
used in Biochemistry was developed by P.L.Privalov in 1964.
8

9. Differential scanning calorimetry:
Principle:
• It is a technique in which the energy necessary to establish a
zero temp. difference between the sample & reference material
is measured as a function of temp.
• Here, sample & reference material are heated by separate
heaters in such a way that their temp are kept equal while these
temp. are increased or decreased linearly
9

10. Differential scanning calorimetry:
• Endothermic reaction: if sample absorbs some amount of heat
during phase transition then reaction is said to be endothermic.
In endothermic reaction more energy needed to maintain zero
temp difference between sample & reference.
E.g. Melting, boiling, sublimation, vaporization, de-solvation
• Exothermic reaction: if sample released some amount of heat
during phase transition, then reaction is said to be exothermic.
In exothermic reaction, less energy needed to maintain zero
temp difference between sample & reference.
E.g crystallization, degradation, polymerization.
10

11. Differential scanning calorimetry:
• DSC Is widely used to measure glass transition temp &
characterization of polymer.
• Glass Transition temp(Tg): Temp at which an amorphous
polymer or an amorphous part of crystalline polymer goes
from hard ,brittle state to soft, Rubbery state.
11

12. Instrumentation:
There are five different types of DSC instrument:
1. Heat flux DSC
2. Power compensated DSC
3. Modulated DSC
4. Hyper DSC
5. Pressure DSC
12

13. 1.Heat flux DSC:
• In heat flux DSC, the difference in heat flow into the sample
and reference is measured while the sample temperature is
changed at the constant rate.
• The main assembly of the DSC cell is enclosed in a
cylindrical, silver heating black, which dissipates heat to the
specimens via a constantan disc which is attached to the silver
block.
• The disk has two raised platforms on which the sample and
reference pans are placed.
13

14. 1.Heat flux DSC:
• A chromel disk and connecting wire are attached to the
underside of each platform, and the resulting chromel-
constantan thermocouples are used to determine the
differential temperatures of interest.
• Alumel wires attached to the chrome discs provide the
chromel-alumel junctions for independently measuring the
sample and reference temperature.
• A separate thermocouple embedded in the silver block serves a
temperature controller for the programmed heating cycle. And
inert gas is passed through the cell at a constant flow rate of
about 40 ml/min .
14

15. Heat flux DSC:
Schematic representation:
15

16. 1.Heat flux DSC:
• In heat flux DSC, we can write the total heat flow dH/dt as,
• dH/dt = Cp dT/dt + f (T,t)
• Where, H = enthalpy in J mol-1
• Cp=specific heat capacity in JK -1 mol-1
• f (T,t )= kinetic response of the sample in J mol-1
• Thus, the total heat flow is the sum of the two terms, one
related to the heat capacity, and one related to the kinetic
response .
16

17. Types of heat flux DSC:
Heat flux DSC
A.Disk Type
Measuring System
B.Cylinder measuring
system
C.Turret-type
measuring system
D.Micro differential DSC
17

18. A.The Disk Type Measuring System– Heat
Flux DSC :
• The disk type measuring system heat exchange takes place
trough a disk which is solid sample support.
• The main heat flow from the furnace passes symmetrically
trough disk with a medium thermal conductivity; this is its
main characteristic.
• In some cases the disks are made with combination of metal
(e.g. platinum) and covered with ceramics. Modification of the
disk type of DSC is very common.
18

19. A.The Disk Type Measuring System– Heat
Flux DSC :
• One is HF-DSC with a triple measuring system. With three
separate locations the measurement of specific heat is
measured with just one run.
•
• In the classic HF-DSC device three measurements must be
made (with an empty crucible, with a sapphire or a known
inert sample and with the investigated sample).
• Another modification is high pressure HF-DSC, which is used
to determine vapour pressures and heats of evaporation. Its
features are high sensitivity and small sample volume
19

20. A.The Disk Type Measuring System– Heat
Flux DSC :Schematic representation
20

21. B.The Cylinder measuring system – Heat flux
DSC:
• In the cylinder type measuring system the heat exchange takes
place between the(big) cylindrical sample cavities and the
furnace with a low thermal conductivity (thermopile).
• Only low heating and cooling rates are possible. The
sensitivity per unit volume is high even with a large sample
volume. This system has a larger time constant than the first
two measuring systems.
• The heat flux DSC operating on Calvet principle is using a
cylinder type measuring system by two sintered alumina
cylinders set parallel and symmetrical in the heating furnace.
21

22. B.The Cylinder measuring system – Heat flux
DSC:
• The crucible used here is produced from stainless steel. The
HF-DSC with the cylinder measuring system is appropriate for
large samples.
• Compared with the other apparatuses, the cylinder type has a
much larger volume and therefore a longer time constant
which can be as long as 40. min
22

23. B.The heat flux DSC with a cylinder- type
measuring System (Calvet):
23

24. C.The turret-type measuring system – HF
DSC :
• In turret type heat exchange takes place via small hollow
cylinders which also serve as sample support. Small hollow
cylinders are used for sample support and for the heat
exchange.
• The turret measuring system is ideal for determining the purity
of metals. The advantage of the turret system is in the heat
transfer from the jacket to the sample, because it goes through
a thin-walled cylinder. This way a very short heat conducting
path is achieved
24

25. C.The turret-type measuring system – HF
DSC :
• The system is very small thus the characteristic time is very
short. No interference between the sample and the present.
• The turret type is special because of a third thermocouple
which measures the thermal inertia. This is a so-called Tzero
DSC technology
25

26. C.The turret type measuring system HF-DSC
26

27. D.Micro differential DSC–modified HF DSC :
• This method is a combination of an isothermal calorimeter and
a HF-DSC mode device.
• In an isothermal calorimeter, the heat generated by the sample,
flows through the thermal resistance into a water jacket.
• The temperature difference across the thermal resistance is
measured.
• Micro DSC has the same ability to measure the thermal
properties as an ordinary DSC device.
27

28. D.Micro differential DSC–modified HF DSC :
• One of the advantages is a very high sensitivity but on the
other hand the temperature range is very narrow (–20 °C to
≈120°C).
• With this type of device it is ideal to study crystallisation
because the cooling and heating rates can be even lower than
0.001 °C/min (with a response time of few seconds) and is also
suitable to determine phase transitions like intermediate phases
between solid and liquid in Liquid crystals
28

29. D.The heat flux Micro differential DSC:
29

30. 2.Power compensation DSC :
• In power compensation DSC, the temperatures of the sample
and reference are kept equal to each other while both
temperatures are increased or decreased linearly.
• The power needed to maintain the sample temperature equal to
the reference temperature is measured. In power compensation
DSC two independent heating units are employed.
• These heating units are quite small, allowing for rapid rates of
heating, cooling and equilibration. The heating units are
embedded in a large temperature- controlled heat sink.
30

31. 2.Power compensation DSC :
• The sample and reference holders have platinum resistance
thermometers to continuously monitor the temperature of the
materials.
• Both sample and reference are maintained at the programmed
temperature by applying power to the sample and reference
heaters.
• The instrument records the power difference needed to
maintain the sample and reference at the same temperature as a
function of the programmed temperatures.
31

32. 2.Power compensation DSC :
• Power compensated DSC has lower sensitivity than heat flux
DSC, but its response time is more rapid.
• This makes power compensated DSC well suited for kinetics
studies in which fast equilibrations to new temperature settings
are needed. it is also capable of higher resolution then heat
flux DSC
32

33. 2.Power compensation DSC :
• All PC DSC are in basic principles the same. But, one of the
special PC DSC is photo DSC. Where direct measurements of
radiation flow occur under a light source.
• This way the degradation of material can also be observed.
The maximum heating rate for not modified PC DSC is up to
500K/min and the maximum cooling rate is up to 400 K/min.
Temperature range of measurement is up to 400 °C with time
constant of only 1.5 s or lower. Sample masses are around 20
mg. Crucibles of different volumes (lower than several ten
cubic millimeter's) are made mostly of aluminum
33

34. Power compensation DSC :
34

35. 3.Modulated DSC
• Modulated DSC uses the same heating and cell arrangement as
the heat – flux DSC method. it is a new technique introduced
in 1993 .
• The main advantage of this technique is the separation of
overlapping events in the DSC scans. In MDSC the normally
linear heating ramp is overlaid with the sinusoidal function
(MDSC) defined by a frequency and amplitude to produce a
sine wave shape temperature versus time function.
• Using Fourier mathematics, the DSC signal is split into two
components: reflecting no reversible events (kinetic) and
reversible events 35

36. 3.Modulated DSC:
T= T0=bt+B sin(wt)
dq/dt=C [b+Bw cos(wt)] +f(t,T)+K sin (wt)
• where, T=temperature
• C=specific heat
• t=time
• w=frequency f(t,T)= the average underling kinetic function once the
effect of the sine wave modulation has been subtracted.
• K= amplitude of the kinetic response to the sine wave modulation.
• [b+Bw cos (wt)]=the measured quantity dT/dt or reversing Curve.
36

37. 3.Modulated DSC:
• MDSC is a valuable extension of conventional DSC. Its
applicability is recognized for precise determination of the
temperature of glass transition and for the study of the energy
of relaxation.
• It has been applied for the determination of glass transition of
Hydroxypropylmethylcellulose films and for the study of
amorphous lactose as well as some glassy drugs
37

38. 4.Hyper DSC:
• The high resolution of PC-DSC or new type of power
compensating DSC provides the best results for an analysis of
melting and crystallization of metals or detection of glass
transition temperature (Tg) in medications.
• Fast scan DSC has the ability to perform valid heat flow
measurements with fast linear controlled rates (up to 500
K/min) especially by cooling, where the rates are higher than
with the classical PC DSC.
• Standard DSC operates under 10 K/ min.
38

39. 4.Hyper DSC:
• The benefits of such devices are increased sensitivity at higher
rates (which enables a better study of the kinetics in the
process), suppression of undesired transformation like solid –
solid transformation etc .
• It has a great sensitivity also at a heating rate of 500 K/min
with 1 mg of sample material.
• This technique is especially proper for the pharmaceutics
industry for testing medicaments at different temperatures
where fast heating rates are necessary to avoid other unwanted
reactions etc
39

40. 5.Pressure DSC
• In pressure DSC, the sample can be submitted to different
pressures, which allows the characterization of substances at
the pressures of processes or to distinguish between
overlapping peaks.
• Applications of this technique includes studies of pressure
sensitive reactions, evaluation of catalysts , and resolution of
overlapping transitions.
40

41. Typical DSC Curve:
41

42. Typical DSC Curve:
• The result of a DSC experiment is a curve of heat flux versus
temperature or versus time.
• There are two different conventions: exothermic reactions in
the sample shown with a positive or negative peak, depending
on the kind of technology used in the experiment.
• This curve can be used to calculate enthalpies of transitions.
This is done by integrating the peak corresponding to a given
transition.
42

43. Typical DSC Curve:
• It can be shown that the enthalpy of transition can be
expressed using the following equation:
△H = KA
• where H is the enthalpy of transition, K is the calorimetric
constant, and A is the area under the curve.
• The calorimetric constant will vary from instrument to
instrument, and can be determined by analyzing a well-
characterized sample with known enthalpies of transition.
43

44. Factors Affecting DSC Curve:
Instrumental factors :
• Furnace heating rate
• Recording or chart speed
• Furnace atmosphere
• Geometry of sample holder/location of sensors
• Sensitivity of the recording system
• Composition of sample containers
44

45. Factors Affecting DSC Curve:
Sample characteristics:
• Amount of sample
• Nature of sample
• Sample packing
• Solubility of evolved gases in the sample
• Particle size
• Heat of reaction
• Thermal conductivity
45

46. Experimental Parameters:
1. Sample preparation
2. Experimental conditions
3. Calibration
4. Resolution
5. Sources of errors
46

47. 1.Sample Preparation:
Sample Types: The DSC can be used to analyze virtually any material
that can be put into a DSC sample pan. This includes:
• Films
• Fibers
• Powders
• Solutions
• Composites
When making quantitative measurements or verifying reproducibility, it
is important to ensure good thermal contact between the sample and
sample pan. The physical characteristics of the sample affect the
quality of this contact.
47

48. 1.Sample Preparation:
• When using powdered or granular samples, spread them
evenly across the bottom of the pan to minimize thermal
gradients. For solid samples, select the side of your sample
with the flattest surface for contact with the pan. After
encapsulating the sample, ensure that the pan bottom is flat. If
it is not, flatten it by pressing the pan bottom on a flat surface.
• NOTE: The contact between the pan and the raised sample
platform is as important as the contact between the sample
and sample pan.
48

49. 1.Sample Preparation:
• NOTE: The oils on your fingers can affect the results of
thermal analysis experiments. Always use tweezers when
handling sample pans and sample material.‘
• If you overfill a pan, the heating or cooling procedures may
cause the sample to boil out, buckle, or explode the pan. If you
are using an Auto-sampler and this occurs so that the Auto-
sampler cannot remove a pan from the cell because of
deformation or boiled-out material, operation is halted until the
problem is corrected.
• Therefore, you should be reasonably familiar with the effects
of heating and cooling procedures on your samples and pans
49

50. Determining sample size:
• Normally, sample weight in DSC experiments is in the range
of 5 to 20 milligrams. If purity determinations are to be
performed, then sample sizes of 1 to 3 milligrams are
recommended.
• Refer to the table below to guide you when selecting the
sample size and heating rates for your experiment.
50

51. Determining sample size:
Type of Measurement Sample Size (mg) Heating Rate (°C/min)
Glass transition 10 to 20 10 to 20
Melting point 2 to 10 5 to 10
Kinetics (Borchardt and
Daniels)
5 to 10 5 to 20
Kinetics (ASTM) 2 to 5* 0.5 to 20
Heat capacity 10 to 70 20**
Purity 1 to 3 0.5 to 1
Crystallinity or oxidative
stability
5 to 10 5 to 10
MDSC 2 to 10 1 to 5
51

52. Selecting a sample pan:
• Selection of the appropriate DSC sample pan and lid is a very
important element of your method development process. The
results you obtain from the use of DSC will be affected by
your choices.
52

53. Selecting a sample pan:
Pan Type Pan Lid Die Set Software Pan
Type
Application
Tzero
Aluminum
Tzero Pan Tzero Lid Black Tzero
Aluminum
Basic
DSC/MDSC
applications
Tzero
Hermetic
Aluminum
Tzero Pan Tzero
Hermetic Lid
Blue Tzero
Hermetic
Aluminum
DSC
applications
which require
hermetic seals
Tzero
Hermetic Alu
minum
Alodined
Tzero
Alodined Pan
Tzero
Hermetic
Alodined Lid
Blue Tzero
Hermetic
Aluminum
Alodined
DSC
applications
which require
hermetic seals
and may
evolve water
Tzero Low-
Mass
Aluminum
Tzero Low-
Mass Pan
Tzero Lid Black Tzero
Aluminum
High-
sensitivity for
low mass of
sample
53

54. 2. Experimental conditions
Heating Rate
• Samples are heated at a rate of 10 or 20°C/min in most cases. •
• Lowering the heating rates is known to improve the resolution
of overlapping weight losses.
• Advances in the technology have made it possible for variable
heating rates (High Resolution TGA) to improve resolution by
automatically reducing the heating rate during periods of
weight loss.
54

55. 2. Experimental conditions:
Purge gas
• Nitrogen is the most common gas used to purge samples in
TGA due to its inert nature.
• Whereas, helium provides the best baseline.
• Air is known to improve resolution because of a difference in
the oxidative stability of components in the sample.
• Vacuum may be used where the sample contains volatile
components, which helps improve separation from the onset of
decomposition since the volatiles come off at lower
temperatures in vacuum. • e.g. oil in a rubber tire product
55

56. 3.(a)DSC Calibration baseline:
Evaluation of the thermal resistance of the sample and reference
sensors measurements over the temperature range of interest
2-step process:
• The temperature difference of two empty crucibles is
measured.
• The thermal response is then acquired for a standard material,
usually sapphire, on both the sample and reference platforms
56

57. 3.(a)DSC Calibration baseline:
• Organic compounds have been
recommended as standards when
studying organic material to
minimize differences in thermal
conductivity, heat capacity, and
heat of fusion and may be used
predominantly at temperatures
below 300 K.
• Amplified DSC signal is
automatically varied with
temperature to maintain a
constant calorimetric sensitivity
with temperature.
57

58. 3(b).DSC Calibration temperature:
• Goal is to match the melting onset temperatures indicated by
the furnace thermocouple readouts to the known melting
points of standards analyzed by DSC
• Should be calibrated as close to the desired temperature range
as possible.
• Heat flow :use of calibration standards of known heat
capacity, such as sapphire, slow accurate heating rates (0.5–2.0
°C/min), and similar sample and reference pan weights
58

59. 3(b).DSC Calibration temperature:
Calibrants:
• high purity
• accurately known enthalpies
• thermally stable
• light stable
• Non-hygroscopic
• Un-reactive (pan, atmosphere)
Metals:
• In °C; J/g
• Sn °C
• Al °Ci
59

60. 3(b).DSC Calibration temperature:
Inorganics
• KNO °C
• KClO °C
Organics
• polystyrene 105 °C
• benzoic acid °C; J/g
• anthracene 216 °C; J/g
60

61. 4.Resolution:
• One of the most important performance characteristics of a
DSC instrument is its resolution.
• This refers to the ability of the DSC to separate or resolve
closely occurring thermal transitions.
• The resolution of a DSC cell is dependent upon its particular
design properties including the mass of the furnace, the
temperature measuring system employed and the response
time of the cell.
61

62. 4.Resolution:
• The low mass of the Pyris 1 DSC along with the use of a
platinum resistance thermometer (PRT) temperature measuring
system provides outstanding inherent resolution.
• The resolution of a DSC is also a function of the given
experimental conditions, including:
 Purge gas
 Sample mass
 Heating rate
62

63. 4.Resolution:
• Enhanced resolution can be obtained using a helium rather
than a nitrogen, air or oxygen purge, due to the significantly
higher thermal conductivity of helium.
• Lower sample masses can provide improved resolution over
larger masses.
• Slower heating rates will yield significantly better resolution
than faster rates.
63

64. 64

65. 5.Sources of errors:
• Calibration
• Contamination
• Sample preparation – how sample is loaded into a pan
• Residual solvents and moisture.
• Thermal lag
• Heating/Cooling rates
• Sample mass
• Processing errors
65

66. Advantages of DSC:
• Instruments can be used at very high temperatures
• Instruments are highly sensitive.
• Flexibility in sample volume/form .
• Characteristic transition or reaction temperatures can be
determined.
• High resolution obtained
• High sensitivity
• Stability of the material.
66

67. Limitations of DSC:
• DSC generally unsuitable for two-phase mixtures.
• Difficulties in test cell preparation in avoiding evaporation of
volatile Solvents .
• DSC is generally only used for thermal screening of isolated
intermediates and products .
• Does not detect gas generation.
• Uncertainty of heats of fusion and transition temperatures
67

68. Applications:
• Metal alloy melting temperatures and heat of fusion.
• Metal magnetic or structure transition temperatures and heat of
transformation.
• Intermetallic phase formation temperatures and exothermal energies.
• Oxidation temperature and oxidation energy.
• Exothermal energy of polymer cure (as in epoxy adhesives), allows
determination of the degree and rate of cure.
68

69. Applications:
• Determine the melting behavior of complex organic materials, both
temperatures and enthalpies of melting can be used to determine
purity of a material.
• Measurement of plastic or glassy material glass transition
temperatures or softening temperatures, which change dependent
upon the temperature history of the polymer or the amount and type
of fill material, among other effects.
• Determines crystalline to amorphous transition temperatures in
polymers and plastics and the energy associated with the transition.
• Crystallization and melting temperatures and phase transition
energies for inorganic compounds.
69

70. Applications:
• Oxidative induction period of an oil or fat.
• May be used as one of multiple techniques to identify an unknown
material or by itself to confirm that it is the expected material.
• Determine the thermal stability of a material.
• Determine the reaction kinetics of a material.
• Measure the latent heat of melting of nylon 6 in a nylon Spandex
fabric to determine the weight percentage of the nylon
70

71. References:
• Skoog, dougla A, F James holler and timothy nieman,
principles of instrumental analysis, 5th edition New york 2001
• Instrumental methods of Chemical analysis-GURDEEP
R.CHATWAL
• http://folk.ntnu.no/deng/fra_nt/other%20stuff/DSC_manuals/Q
DSC/Selecting_a_Sample_Pan.htm#Selecting_a_Sample_Pan
_for_the_Tzero_Press
• file:///H:/data0/mpat%20presentation/analysis/differential-
scanning-calorimetry-a-review-11-22.pdf
71

72. 72