M pharm chemistry department

1. R. C. Patel Institute of Pharmaceutical Education and
Research, Shirpur.
Name - Rina Pandurang
Patil
Stream - 1 st yr M Pharm
(Pharmaceutical
Chemistry )
Roll No. 08
DSC & TGA

2. Thermal Analytical Techniques
“Thermal Techniques involves the measurement of the
dynamic relationship between temperature and some
property of a system such as mass, heat of reaction or
volume.”
• Thermal methods of chemical analysis are as follows -
1) Thermogravimetric analysis (TGA) - Mass of the sample is
monitored as a function of temperature or time.
2) Differential Thermal Analysis (DTA) -Temperature difference
between sample and reference substance is monitored as a
function of either time or temperature as the two specimens
are subjected to identical temperature regimes in an
environment heated or cooled at a controlled rate.
3) Differential Scanning Colorimetry (DSC) - Difference in the
heat that flows into the sample and that which flows into the
reference substance is monitored as a function of
temperature or time.

3. 5) Thermomechanical Analysis (TMA) – Dimension of sample is
measured as the temperature is altered.
6) Derivative Differential Thermal Analysis (DDTA) - A method for
precise determination in thermograms of slight temperature
changes by taking the first derivative of the differential thermal
analysis curve (thermogram) which plots time
versus differential temperature as measured by
a differential thermocouple.
 In thermal analytical techniques the data obtained in the form of
continuously recorded curves is known as thermal data.
4) Dynamic Mechanical Analysis (DMA) – Mechanical property of
sample is monitored as the sample is subjected to stress.

4. Sr. No. Name of the
Technique
Abbreviation Instrument
Employed
Parameter Measured Graph
Plotted
1 Thermogravimetric
Analysis
TGA Thermo
balance
Mass Mass vs.
Temperature
2 Differential
Thermal Analysis
DTA DTA Apparatus vs.
Temperature
3 Derivative
Differential
Thermal Analysis
DDTA DTA Apparatus Differential
Temperature
vs. Time
4 Differential
Scanning
Colorimetry
DSC Calorimeter dH /dt dH /dt vs.
Temperature
5 Dynamic
Mechanical
Analysis
DMA DMA
Apparatus
Mechanical Property Mechanical
Property vs.
Stress
6 Thermomechanical
Analysis
TMA Dilatometer Volume or length Volume or
length vs.
Temperature
Table 1 : Thermal Methods of Analysis

5. 1. Thermogravimetric Analysis (TGA)
“In this technique the mass of sample is monitored as a
function of temperature.”
• The following techniques of analysis are adopted –
1) Isothermal or Static TGA – In this type, sample is maintained
at constant temperature for given time during which its weight
is recorded.
2) Quasistatic TGA – In this type, sample is heated to constant
weight at each of series of increasing temperature.
3) Dynamic TGA – In this type, the sample is subjected to
continuous increase in temperature linear with time.

6. Principle
• TGA is performed by gradually increasing the temperature of
sample in a furnance and its weight is measured on an
analytical balance that remains outside of furnance. In TGA,
mass loss is observed if a thermal event involves loss of a
volatile component.
• A typical TGA curve is shown in Fig. 1
Fig. 1 – Typical TGA curve

7. Instrumentation
A modern thermobalance consist of the components (Fig.2) -
(1) Recording balance
(2) Sample holder
(3) Furnance
(4) Furnance temperature programmer or controller
(5) Recorder
Fig.2 – Schematic Diagram of Modern Thermobalance

8. (1) Recording balance
• It is most important component of thermobalance. A good
balance must fulfil the following requirements:
1) Its accuracy, sensitivity, reproducibility and capacity should be
similar to those of analytical balance.
2) It should have an accurate range of automatic weight
adjustment.
3) It should have high degree of mechanical and electronic stability.
4) It should give rapid response to weight changes.
5) It should be unaffected by vibrations.
6) It should be simple to operate and versatile.
• Recording balances are mainly of two types –
(1) Deflection type instrument
(2) Null type instrument

9. 1) Deflection type balances – They are of following types
(1) Beam Type
In these types, there occurs conversion of beam deflection
about fulcrum into suitably identifiably weight changes curve
by photographic recorded trace, recorded signals generated
by suitable displacement measuring transducers or curve
drawn electromechanically.
(2) Helical type
In these types, there occurs elongation or concentration
of spring with weight change. The quartz fibre is generally use
as spring.
(3) The Cantilevered Beam
In these types, one end of the beam is fixed and other end
on which sample is placed is free to undergo deflection.
(4) Torsion wire
In these types, beam is attached to taut wire which acts as
fulcrum. The wire is firmly fixed at either or both ends so that
deflections of beam are proportional to weight changes and
torsion characteristics of wire.

10. Fig.3 (a) Deflection Type Balances Fig.3 (b) Null Type Balances
2) Null type instrument –
In these types, there should be a sensor to detect
deviation of balance beam from its null position. Then, a
restoring force, of either electrical or mechanical weight
loading, is applied to beam to restore its null position from
horizontal or vertical norm. The restoring force is proportional
to weight change and the force is recorded directly or by
transducer of some type Fig.3(b).

11. (2) Sample holder
• Depending upon the nature of sample, its weight and quantity
to be handled, different sizes and shapes of sample holders
known as crucibles are employed. These are constructed from
various materials like glass, quartz, aluminium, stainless steel,
platinum etc.
• These generally of two types:
1) Shallow pan for holding sample which eliminates gas vapours
or volatile matter by diffusion during heating.
2) Deep crucibles for general purpose are employed in such
cases where side reaction and or partial equilibrium is to be
desired.
3) Loosely covered crucibles are mainly used in self generated
atmosphere studies.
4) Retort cups resembles alchemist’s retort. These are useful in
boiling point studies.

12. (3) Furnance
• The furnance and control system should be designed to produce
a linear heating rate over the whole working temperature range
of furnance. The choice of furnance heating element and
furnance depend upon temperature range being studied.
• For 1100 0C, the material of furnance is “Kanthal” or “Nichrome”
wire or ribbon. If a wire is being used, it should be wound
“Coiled coil” fashion to accommodate differential thermal
expansion of various component.
• For temperature between 1100 0C and 15000C one should use
platinum or any alloy of platinum and rhodium. By using
platinum rhodium alloy having rhodium content of 40% one can
use furnance up to 1750 0C.
• For temperature above 1750 0C, tungsten or molybdenum may
be employed in reducing atmosphere.

13. • The size of furnance is important factor. For example, a main
advantage of low mass furnance is it cools very quickly but its linear
temperature rise is very difficult to control. On other hand a high
mass furnance may hold isothermal temperature but it requires
comparatively more time to achieve the required temperature.
• It becomes easier to obtain a large uniform hot zone in high mass
furnance. With small mass furnance it becomes difficult.
Fig4 – Position of Furnance w.r.t. Balance
• The position of furnance relative to balance is important. With
some balances like quartz fibre spring balance, the furnance is below
weighing system but with beam balances several choices are
possible.

14. (4) Furnance Temperature Programmer Or Controller
• There are the controllers which can provide gradual rise of
temperature at a fixed rate. This device has a course and fine
control knobs through which desired temperature with
respect to rate/time can be obtained. This controlling is done
by increasing voltage through heating element by motor
driven variable transformer or by different thermocouple.
• This can be done by number of ways. The most common
method is a thermocouple. For measuring 11000C, chromel or
alumel thermocouples made up of alloys of platinum and
rhodium are employed. For higher temperature, tungsten or
rhenium thermocouples are used extensively.
• The position of temperature measuring device relative to
sample is very important. This can be adjusted in one of the
following ways as in fig.5
(1) In fig. (a), thermocouple is placed near sample container and
it has no contact with sample container. This is not good
arrangement especially where low pressure is employed.

15. (2) In fig. (b), thermocouple is placed inside the sample holder but
not in contact with it. This arrangement is better than (1) because it
responds to small temperature changes.
(3) In fig.(c), thermocouple is placed either in contact with sample or
with the sample container. This is best arrangement of sample
temperature detection.
Fig.5– Position of thermocouple in thermobalance

16. (5) Recorder
• The reading systems are mainly of two types
a) Time based potentiometric strip chart recorder
b) X-Y recorders
• Electrical supply dully amplified is fed to recorder chart. The
speed of recorder is variable and adjusted according to use.

17. Factors Affecting Thermogravimetric Results
1) Instrumental factors
2) Sample Characteristics
1) Instrumental Factors
• If a system is studied by different thermobalances the sample of
TG curve obtained in each class will vary from instrument to
instrument.
a) Heating Rate - If a substance is being heated at a fast heating
rate, the temperature of decomposition will be higher than that
obtained at a slower rate of heating.
b) Effect of furnance atmosphere - There is marked influence of
furnance atmosphere on TG curve. For instance, decomposition
of calcium carbonate will take place at much higher temperature
if carbon dioxide rather than nitrogen is used as surrounding
atmosphere.

18. •The common atmospheres involved in thermogravimetry are as
follows–
1) Static Air – In this type air from atmosphere is allowed to flow
through furnance
2) Dynamic Air – In this type compressed air from a cylinder is
allowed to flow through furnance at a measured flow rate.
3) Inert Atmosphere – Nitrogen gas (oxygen free) is used as inert
environment.
c) Sample Holder - Geometry of the sample holder can change the
slope of TG curve. Sample holders range from flat plates to deep
crucibles of various capacities.
• Generally a shallow dish is preferred over a high form cone shape
crucible because in former there is rapid gaseous exchange between
sample and surrounding atmosphere.
• When atmosphere is the solely gas involved in reaction the
geometry of container has no effect on slope of TG curve.

19. 2) Sample Characteristics
a) Weight of sample - If a large sample is used, there occurs a
deviation from linearity as temperature rises. This particularly
found to be true in the case of fast exothermic reaction. An
example of this is the evolution of carbon monoxide during
decomposition of calcium oxalate to calcium carbonate.
b) Sample particle size – With a particle size of smaller
dimension the decomposition takes place earlier, while with
greater particle size decomposition proceeds only at higher
temperature. The decomposition temperature decreases with
decrease in sample particle size.
c) Heat of reaction – The effect of heat of reaction of sample on
TG curve has been studied by Newkirk. The heat of reaction
will alter difference between the sample temperature and the
furnance temperature. If the heat effect is exothermic or
endothermic, this will cause the sample temperature to lead
or lag behind the furnance temperature.

20. d) Compactness of Sample – A compressed sample will decompose at
higher temperature than a loose sample.
e) Previous History of sample – TG studies shows that magnesium
hydroxide prepared by precipitation method has a different
temperature of decomposition from that of naturally occurring
material.
Applications of TGA
1) Automatic Thermogravimetric analysis.
2) Evaluation of gravimetric precipitate.
3) Evaluation of suitable temperatures.
4) Testing of purity of samples.
5) Curie point determination.

26. Sample
holder

36. 3. Differential Scanning Colorimetry (DSC)
“Difference in the heat that flows into the sample and that
which flows into the reference substance is monitored as a
function of temperature or of time.”
History
The technique was developed by
E. S. Watson & M. J. O' Neill in
1962

37. • DSC is a thermoanalytical technique in which the difference in the
amount of heat required to increase the temperature of a sample and
reference is measured as a function of temperature. Both the sample
and reference are maintained at nearly the same temperature
throughout the experiment. Generally, the temperature program for a
DSC analysis is designed such that the sample holder temperature
increases linearly as a function of time. The reference sample should
have a well-defined heat capacity over the range of temperatures to be
scanned.
Principle

38. •A Typical DSC Curve is shown in fig.10
Fig 10 - A Typical DSC Curve

39. Instrumentation
• There are three different types of DSC instruments: power-
compensated DSC, heat-flux DSC, and modulated DSC. Each
produces a plot of power or heat flow versus temperature,
called as thermogram.
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 a constant rate. Both sample and reference are
heated by a single heating unit. Heat flows into both the
sample and reference material via an electrically heated
constant thermoelectric disk, as shown in Figure 11. Small
aluminium sample and reference pans sit on raised platforms
on the constant disk. Heat is transferred through the disks and
up into the material via the two pans. The differential heat
flow to the sample and reference is monitored by Chromel

40. Fig. 11 - Heat Flux DSC
constant area thermocouples formed by the junction between the
constant platform and Chromel disks attached to the underside of
the platforms. The differential heat flow into the two pans is directly
proportional to the difference in the outputs of the two
thermocouple junctions. The sample temperature is estimated by
the Chromel- alumel junction under the sample disk.

41. 2) Power Compensated DSC
• In power compensated 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.
• The sample and reference are heated separately in power
compensated DSC, as shown in Figure 12. The pan
temperatures are monitored using thermocouples attached to
the disk platforms. The thermocouples are connected in series
and measure the differential heat flow using the thermal
equivalent of Ohm’s Law
dq/dt=∆T/RD
Where dq/dt is the heat flow, ∆T is the temperature
difference between the reference and sample, and RD is the
thermal resistance of the disk platform. The heat flow to each
pan is adjusted to keep their temperature difference close to
zero while the furnance temperature is increased linearly.

42. Fig.12 - Schematic of a power compensated DSC system. The sample and
reference pans are heated separately. The heat flow to each pan is adjusted to
keep their temperature difference close to zero. The difference in heat flow is
recorded.

43. 3) Modulated DSC
• Modulated temperature DSC (MDSC) is an extension of DSC.
The same heat flux DSC cell is used for MDSC, but a sinusoidal
temperature oscillation (modulation) is overlaid on the
conventional linear temperature ramp. This results in the
heating rate at times being faster or slower than the
underlying linear heating rate.
4) Hyper-DSC -
• High speed DSC (hyper-DSC) as a tool to measure the
solubility of a drug within a solid or semi-solid matrix.

44. Factors Affecting DSC
1. Sample Shape: The shape of sample has little effect on
quantitative aspect of DSC but has more effect on qualitative
aspects. However sample in the form of a disc film or
powder spread on the pan are preferred. In the case of
polymeric sheets a disc cut with a cork borer gives good
results.
2. Sample size: About 0.5 to 10 mg is usually sufficient. Smaller
samples enable faster scanning, give better shaped peaks
with good resolution and provide better contact with
gaseous environment. On the other hand, with large
samples, smaller heats of transition may be measured with
greater precision.

45. A DSC Application in Biology
1 Analysis of proteins
2 DSC of Nucleic Acids.
3 Analysis of Lipids.
4 Analysis of Carbohydrates.
5 Analysis of Ab
B DSC Application in Nanoscience
1 Quantification of pharmaceutical Nanosolids.
2 Thermal characteristics of nanostructured lipid carriers (NLC's)
3 Thermoanalysis of colloidal nanoparticles.
4 Glass transition measurement of macromolecule in nanophases.
5 characterization of ion- chelating nano carriers.
6 self- Assembly study of supramolecular nanostructures.
Recent Applications in DSC

46. Applications of DSC .....
1. Glass Transition Temperatures When heating a sample at a certain temp. Plot will
be shift downward suddenly. Which means more heat flow & heat capacity increases because of
glass transition. ( It is reversible transition in amorphous material from a hard brittle state into
molten rubber like state )
2. Determination of heat capacity It is used to determine heat capacity, when
we start heating two pan's, the computer will plot difference in heat output of two
heaters against temp. & this is the heat absorbed by substance against temp.
3. Crystallization When polymers fall into these crystalline arrangements, they give of
heat. This drop in the heat flow appear as a big peak in the plot of heat flow Vs
temp.
4. The temp. At which highest point in the peak is usually considered to be the
polymer crystallization temp. Also area of the peak can be measured which
tellus us the latent energy of crystallization of polymer.
5. Melting If polymer is heated fast it's Tc eventually reach another thermal
transition called melting.
6. Crystallinity and Crystallization Rate
7. Reaction Kinetics
8. It gives a wealth of information regarding both of the physical & energy
property of the substances.

47. References-
1) Gurdeep R. Chatwal, Sham K. Anand, “Instrumental Methods of
Chemical Analysis, (Analytical Chemistry)”, Himalaya Publishing
House, Pvt. Ltd., Mumbai, Page no. 2.701 - 2.780.
2) Douglas A. Skoog, F. James Holler, Stanley R. Crouch, “Principles of
Instrumental Analysis”, 6th edition, Page no. 894 – 908.
3) Dr. A. V. Kasture, S. G. Wadodkar, Dr. K. R. Mahadik, Dr. H. N.
More, “Pharmaceutical Analysis”, Vol. 2, 19th Edition, June 2010,
Nirali Prakashan, Pune, Page n. 258 – 263
4) Hohne G, Hemminger W, Flammersheim H-J. Differential
Scanning Calimetry: An Introduction for Practitioners. Berlin,
Germany: Springer-Verlag, 1996 [Google Scholar].
5) Privalov PL, Potekhin SA. Scanning microcalorimetry in
studying temperature-induced changes in proteins. Methods
Enzymol 1986;131:4–51 [PubMed] [Google Scholar]
6) [2.3]
http://www.colby.edu/chemistry/PChem/lab/DiffScanningCa
l.pdf

48. 7 ) M. E. Brown introduction to thermal analysis:
Techniques and application, second edition,
Springer,2007 .
8 ) Paul Gobbot , principles and Applications of thermal
analysis, Blackwell publishing.
9) Perkin Elmer, TGA manuals.
Palma R, Curmi PMG.
10) Computational studies on mutant protein stability: the
correlation between surface thermal expansion and protein
stability. Protein Sci 1999;8:913–920 [PMC free article]
[PubMed] [Google Scholar]