Thermal analysis techniques monitor a property of a sample against temperature while the sample is heated in a controlled atmosphere. There are several types of thermal analysis including differential scanning calorimetry (DSC), differential thermal analysis (DTA), and thermal gravimetric analysis (TGA). DSC measures the heat flow into or out of a sample during heating or cooling. DTA monitors the temperature difference between a sample and inert reference as heat is applied. These techniques are useful for characterizing pharmaceutical samples and studying thermal transitions such as glass transitions, crystallization, and melting.

1. THERMAL
TECHNIQUES
BY:- AMAN KUMAR MAHTO
M.PHARM (1ST SEMESTER)
PHARMACEUTICAL CHEMISTRY Presentation Date: 30/10/2018

2. THERMAL TECHNIQUES
 Thermal Techniques or Thermal Analytical Techniques -
are group of techniques in which a property of a sample is
monitored against temperature (or time), while the
temperature of the sample in a specified atmosphere is
programmed.[by ICTAC]
 These methods are used for analytical purpose hence the
word Thermal Analysis is used more often.
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3. OBJECTIVES
 Studying the behaviour of pharmaceuticals by different
thermal analysis instruments, under different conditions and
then comparing the results is another objective.
 Common applications used in thermal analysis incorporate
the categorization of the physicochemical attributes of
crystalline solids and the discovery and classification of
polymorphic forms.
 Differential techniques are used to review kinetics in the
solid-state, which includes accelerated stability study,
decomposition and the aging effects on various formulations.
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4. Principle parts of Thermal Analysis
 Thermal analysis usually consists of the following parts:
 Sample holder/compartment for the sample.
 Sensors to detect/measure a property of the sample and the
temperature.
 An enclosure within which the experimental parameters
(temperature, rate, environment) may be controlled.
 A computer to control data collection and processing.
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5. Thermal analysis types
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6. THERMAL ANALYSIS TYPES
 Differential Scanning Calorimetry
(DSC)
 Measure heat absorbed or liberated during
heating or cooling
 Differential Thermal Analysis (DTA)
 They are use for thermal investigation where
thermal change can be observed and
characterised
 Thermal Gravimetric Analysis (TGA)
 Measure change in weight during heating
or cooling
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7. Thermal transitions

Glass transition
temperature
Crystallization
temperature
Melting
temperature
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8. DIFFERENTIAL SCANNING CALORIMETRY
(DSC)
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9. Differential Scanning Calorimetry
 Principle : DSC measures differences in the amount of heat
required (i.e., heat-flow) to increase the temperature of a
sample and a reference as a function of temperature.
 A DSC consists of a cell, which is the heart of a DSC.
 The cell is connected with a gas inlet through which different
gas are purged depending on the data required.
 Based on the DSC cells there are two primary types:
1. HEAT FLUX
2. POWER COMPENSATION
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10. Types of DSC instrument
 Heat Flux DSC
 Routine applications
 Near / at line testing in harsh
environment
 Automated operation
 Cost-sensitive laboratories
 Power Compensation DSC
 High resolution / high
sensitivity research studies
 Absolute specific heat
measurement
 Very sensitive to
contamination of sample
holders
Heat flux DSC Power compensation DSC
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11. Heat flux DSC (Hf-DSC)
 This consists of a large single furnace which acts as an infinite
heat sink to provide or absorb heat from the sample.
 The key components are the sample pan (typically an aluminium
pan and lid) which is combined with the reference pan (always
the same material as the sample pan, aluminium).
 Nitrogen is the most common gas used but alternate inert gas is
helium or argon.
 The heat flux DSC is based in the change in temperature DT
between the sample and reference.
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12. Hf-DSC curve
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13. Power compensation (Pc-DSC)
 Small individual furnaces use different amounts of power to maintain
a constant DT between sample and reference and the advantage here
include faster heating and cooling, and better resolution.
 This type of cell, with two individually heated with platinum heater,
monitors the difference between the sample and reference.
 Platinum resistance thermometers track the temperature variations for
the sample and reference cells.
 Holes in the compartment lids allow the purge gas to enter and contact
the sample and reference.
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14. Instrumentation of DSC
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15. DSC graph
.
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16. Experimental parameters
 Sample preparation
 Experimental conditions
 Calibration
 Heating and cooling rates
 Resolution
 Source of errors
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17. Sample preparation
 Accurately weighed samples (3-20mg, usually 3-5mg for simpler
powders).
 Small sample pans (0.1 mL) of inert or treated metals (Al, Pt).
 Several pan configuration should be used for the sample and the
reference.
 Material should completely cover the bottom of the pan to ensure
good thermal contact.
 Avoid overfilling the pan to minimize thermal lag from the bulk of
the material to the sensor.
 Small sample masses and low heating rates increase resolution, but
at the expense of sensitivity.
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18. Sample shape
 It is recommended that the sample is as thin as possible and
covers as much of the pan bottom as possible.
 Samples in the form of cakes (as in case of polymers) must
preferably be cut rather than crushed to obtain a thin sample.
 Crushing the sample, whether in crystalline form or a polymer,
induces a stress, which can in turn affect the results.
 In most case lid should always be used in order to more
uniformly heat the sample and to keep the sample in contact
with the bottom of the pan.
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19. Sample Pans
 Lightest, flattest pans are known to have the least effect on the
results obtained from a DSC.
 Crimped pans on the other hand provide the highest sensitivity
and resolution.
 Hermetic pans are used where the sample is expected to have
some volatile content. These pans prevent evaporation.
 Two main reasons for the use of these pans are –
i. The Tg of a polymer or amorphous material shifts with
volatile content.
ii. Evaporation peaks look just like melting endotherm.
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20. Sample Weight
 Though 5 to 10 mg is considered to be an appropriate sample
weight for a DSC test, selection of the optimum weight is
dependent on a number of factors: the sample and the change in
heat flow due to the transition of interest should be in the range of
01 – 10 mW.
 For polymer Tg or melting sample the mass should be >>10mg.
 Polymer composites or blends the sample mass is > 10mg.
 The accuracy of the analytical balance used to measure the sample
weight should be accurate to ±1%.
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21. Experimental Conditions
1. Start temperature
 Generally, the baseline should have 2 minutes to completely stabilize
prior to the transition of interest.
 Therefore, at 10oC/min heating rate the run should start at least 20oC
below the transition onset temperature.
2. End temperature
 Allowing a 2-min baseline after the transition of interest is considered
appropriate in order to correctly select integration or analysis limits.
 Care should be taken not to decompose samples in the DSC; it not only
affects the baseline performance but the cell life.
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22. Experimental Conditions
3. Reference pan
 A reference pan of the same type used to prepare the sample should be
used at all times.
 A material in the reference pan that has a transition over the temperature
range of interest should never be used.
4. Heating rate
 Heating the samples at low heating rates increases resolution by providing
more time at any temperature.
 Transitions due to kinetic processes (crystallization) are shifted to lower
temperature at highest cooling rates or higher temperatures at high heating
rates.
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23. DSC Calibration
 Calibration of DSC is done using Indium metal.
 Calibrating an instrument with a metal when pharmaceuticals are
to be studied appears to be not appropriate.
 To overcome this, an effort has been made to calibrate DSC with
pharmaceuticals.
 The true m.p. of indium metal is 156.7oC and the observed in
calibration is 157.4oC.
 It is 0.7oC high and the instrument values must be adjusted down
to accommodate the true melting temperature.
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24. Sources of errors
 Calibration
 Contamination
 Sample preparation
 Residual solvents and moisture
 Thermal lag- heating/cooling rates
 Processing errors
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25. Advantages and disadvantages of DSC
 Advantages
 Widespread study of thermal properties on an extensive range of
sample types.
 Increased sensitivity for detection of weak transitions
 Small sampling requirements – a fraction of mg can be used.
 Disadvantages
 Usually limited to small sample sizes.
 Accuracy : transitions can be shifted by as much as 40oC.
 Thermogram are often complex and difficult to interpret fully.
 Confusion can arise unless care is exercised in the interpretation of the
thermograms.
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26. Pharmaceutical applications of DSC
 Quantitative and Qualitative analysis.
 Characterization –
 melting point,
 heat of fusion,
 specific heat capacity, etc.
 Enhanced analysis of polymorphism
 Detection of low level amorphous content
 Detection of low energy transitions
 Stability tests
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27. DIFFERENTIAL THERMAL ANALYSIS
(DTA)
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28. Differential Thermal Analysis
 Principle :
 Monitoring of the temperature difference between a
sample and an inert reference as the heat is applied to the
system.
 Endothermic and Exothermic changes in the sample lead
to characteristic deviations in temperature, which can be
used for qualitative and quantitative analyses.
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29. Instrumentation
Apparatus for DTA consists of:
 Sample and reference holder
 A furnace
 A detector
 An amplifier
 A recorder
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30. Schematic representation of DTA curve
.
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31. Factors affecting result in DTA
 Sample weight
 Heating rate
 Particle size
 Atmospheric condition
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32. Advantage and Disadvantage
ADVANTAGES
 Can be operated even at
very high temperature.
 High sensitivity.
 Accuracy.
DISADVANTAGE
 Reaction or transition
estimation is only 20% to
50% in DTA.
 Uncertainty in heat of
fusion.
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33. Applications of DTA
 Qualitative and Quantitative estimation of minerals.
 Analysis of biological material (e.g., assay and thermal
stability testing of tetanus toxoid).
 Also used for the thermal stability studies of inorganic compounds
and complexes (e.g., zeolites ).
 To determine melting point, boiling point and decomposition
temperature of organic compounds.
 Widely used for the quality control of a large number of
substances like cement, glass, soil etc.
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34. THERMOGRAVIMETRIC ANALYSIS
(TGA)
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35. Thermogravimetric Analysis (TGA)
 Principle : TGA measures the amount and the rate
of change in weight of a sample with respect to
temperature (or time).
 Instrument : The instrument used for
thermogravimetry is “thermobalance”, and the data
recorded is in the form of curve known as
“thermogram” or “TG curve”.
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36. Instrumentation
 Basically TGA consists of four major
parts –
a) Thermocouple
b) Furnace
c) Auto sampler
d) Microgram balance
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37. Instrumentation
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38. Instrumentation
 The balance is used to record the weight. Its sensitivity
is usually of order of 1microgram.
 The furnace can rise the temperature as high as 1000oC
which is made of quartz.
 The thermocouple sits right above the sample and it
indicates the temperature. The thermocouple should not
be in touch with the sample which is in the pan.
 The auto sampler helps to load the sample on to the
microbalance.
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39. Factors affecting TG curve
 The major factors affecting the recorded mass (m) and temperature
(T) in thermogravimetry are -
 Condensation and reaction (m)
 Electrostatic effects (m)
 Heating rate(T)
 Gas flow (T)
 Sample holder (T)
 Sample size and packing (T)
 Fortunately, most of the factors can be controlled or the data
corrected for their influence.
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40. TGA curve of Calcium Oxalate (CaC2O4)
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41. Applications of TGA
 The water content of a sample can be analysed by TG.
 It can also differentiate between the adsorbed water and constitutional
water.
 In proximate analysis of coal and other similar fuels.
 To measure the oxygen content in the superconductors.
 Oxidative stability.
 Determination of rancidity of edible oils.
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42. REFERENCES
 Analytical Chemistry (A Modern Approach to Analytical Science) - by
M. Mermet, M. Otto, M. Widmer, 2nd edition, WILEY-VCH Verleg
Gmbh & Co. KGaA, page no. 373-388.
 Principles and Practice of Analytical Chemistry - by F.W. Fifield &
D. Kealey., 5th edition (year-2000)., Blackwell Publishing., (page no.
477-493).
 Instrumental Methods of Analysis - by Hobart H. Willard, Dynne L.
Merritt, Jr., John A. Dean, & Frank A. Settle, Jr., 7th edition (year-
1988), Wadsworth publication, page no. 761-777.
 Thermal Analysis Techniques – K.H. Tan (University of Georgia,
Athens, Georgia), B.F. Hajek (Auburn University, Auburn, Alabana),
I. Barshad (University of California, Berkeley, California) (Abstract.,
Published on-1986)., page no. 151.
 https://link.springer.com/article/10.1007/s40828-015-0008-y
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43. THANKING YOU
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