Thermal Analysis

Dr. Mohammad Shariare

Assistant Professor
North South University 1
 Introduction
• Thermal analysis is defined as “series of techniques for
measuring the temperature dependency of a physical property
of a certain substance while varying the temperature of the
substance according to a specific program.”
• Physical properties include mass, dimension, dynamic
characteristics, and others.
• Depending on the physical properties to be measured, the
techniques of thermal analysis is selected

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 Introduction
• Conventionally thermal analysis has been mainly
employed in measurements for research and
development,
development but in recent times it is used in many
practical applications, as the testing standards on the
basis of thermal analysis have been established, for
example, in quality control in the production field,
field
process control and material acceptance inspection.

• It is also applied in wide fields, including polymer,

glass, ceramics, metal, explosives, semiconductors,
medicines, and foods.

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Common Thermal Analysis Methods and the Properties Measured

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 ABBREVIATIONS
• DSC- Differential Scanning Calorimetry
• TGA- Thermogravimetric Analysis
• TMA- Thermomechanical Analysis
• Hf- Heat of Fusion
• Tm - Melting Temperature, extrapolated endothermic
onset temperature
• Tp- Peak Melting endothermic Temperature
• Hc-Heat of exothermic Crystallization
• Tc- Crystallization Temperature, extrapolated exothermic
onset temperature
• Tg -Glass transition temperature

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Basic Principles of Thermal Analysis

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 Thermal Analysis of Pharma
Materials
• DSC,TGA/DTA and TGA/DTA-IR are often used for
characterisation of pharma materials.

• DSC, alone or in combination with hot-stage

microscopy, is able to differentiate between different
polymorphic structures and, by using different
heating rates, can investigate the transformations
which occur during the polymorphic transformation.

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 Thermal Analysis of Pharma
Materials
• TGA is often used to measure residual
solvents and moisture, but can also be used to
determine solubility of pharma materials in
solvents.
• Analysis of pharma materials is probably the
largest area of application for thermal analysis.

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 Thermal Analysis
• Differential Scanning • Thermal Gravimetric
Calorimetry (DSC)
Analysis (TGA)
– Measure heat absorbed or
– Measure change in
liberated during heating or
cooling weight during heating or
cooling

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THERMOGAVIMETRIC
ANALYSIS
(TGA)

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 Thermogravimetric Analysis (TGA)
• Principle: TGA measures the amount and the rate of
weight change of a material with respect to
temperature or time in controlled environments.

• A TGA consists of three major parts a furnace,

1. A microgram balance,
2. An auto sampler and
3. A thermocouple.

02 January 2013 11
 GENERAL PRINCIPLES INVOLVED IN
THERMOGRAVIMETRY
• Instrument: Instrument used for thermogravimetry is
“Thermobalance”. Data recorded in form of curve known as
‘Thermogram’.

• The furnace can raise the temperature as high as 1000°C

which is made of quartz.
• The auto sampler helps to load the samples on to the
microbalance.
• The thermocouple sits right above the sample.
• Care should be taken at all times that the thermocouple is not
in touch with the sample which is in a platinum pan.

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Thermogravimetric Analysis
(TGA)
• A technique that permits
the continuous weighing
of a sample as a
function of temperature
and/or as a function of
time at a desired
temperature

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 instrumentation
GAS IN BALANCE
WEIGHT
CONTROLLER
GAS-TIGHT
ENCLOSURE

SAMPLE

HEATER
SAMPLE TEMP.

POWER FURNACE TEMP.

TEMPERATURE PROGRAMMER
Thermogravimetric Analysis
(TGA)

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Interpretation of TG and DTG curves
i. The sample undergoes no decomposition
with loss of volatile products over the
temperature range shown but solid phase
transformation, melting ,etc can not be
detected by TG,
ii. The rapid initial mass loss is characteristic of
desorption or drying. If it is true, then re-run
the sample should result in type (i) curves,
iii. Single stage decomposition,
iv. Multi-stage decomposition with relatively
stable intermediates : provide information
on the temperature limit of stability of
reactants and intermediate products and
also stoichiometry,
v. Multi-stage decomposition with no stable
intermediate product. However heating-rate
effect must be considered. At low heating
rate, type (v) resemble type (iv). At high
heating rate, type (iv) and (v) resemble type
(iii) and lose all the details,
vi. Gain in mass due to reaction with
atmosphere, e.g. oxidation of metals,
vii. Oxidation product decompose again at
higher temperature; this is not often
encountered.

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Examples of TGA Curves

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 Sample Preparation
• Sample preparation has a significant effect in
obtaining good data.
• It is suggested that maximizing the surface area of
the sample in a TGA pan improves resolution and
reproducibility of weight loss temperatures.
• The sample weight affects the accuracy of weight
loss measurements.
• Typically 10-20mg of sample is preferred in most
applications.
• Whereas, if the sample has volatiles 50-100mg of
sample is considered adequate.
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 Experimental Conditions
• Heating Rate
• Purge gas

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. 19
 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.
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 Calibration
• Blank test
• Calibration of mass changes
• Calibration of temperature

Calibration- Blank test

• Without sample, air is passed at 20 ml/mm, and the
temperature is raised up to 1000 °C at heating rate of 10°C
min-1.
• By this blank test, the general condition of the apparatus can
be known.

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 Calibration- Calibration of mass
changes
• Since the TGA is usually measured by the rate of the weight
change to the sample weight, calibration of absolute value of
weight is hardly necessary.

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 Calibration-Calibration of
temperature
• Based on the TGA data, thermal stability of materials and
their compositions can be predicted depending on the
weight changes caused by evaporation, dehydration,
oxidation and decomposition, up to temperatures as high
as 1000°C.

• A typical example is the TGA of calcium oxalate hydrate,

heated to 1000°C which shows three steps in its
decomposition curve.

• The weight loss data is recorded every half second

throughout the run time.

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TGA Curve of Calcium Oxalate

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 Applications of TGA
There is a wide range of applications of TGA, e.g,
• Composition of multi-component system
• Thermal stability of materials
• Oxidative stability of materials
• Estimated lifetime of a product
• Decomposition Kinetics of materials
• The effect of reactive or corrosive atmosphere on
materials
• Moisture and volatiles contents on materials.
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 Summary of Pharmaceutically Relevant
information Derivation from TGA Analysis

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DIFFERENTIAL SCANNING
CALORIMETRY
(DSC)

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Differencial Scanning Calorimetry
(DSC)
• A calorimeter measures the heat into or out of a
sample.
• A differential calorimeter measures the heat of a
sample relative to a reference.
• A differential scanning calorimeter does all of the
above and heats the sample with a linear temperature
ramp.
• Endothermic heat flows into the sample.
• Exothermic heat flows out of the sample.

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 Differential Scanning Calorimetry (DSC)

Exothermal dQ/dT
Temperature

 DSC measures differences in the amount of heat required to increase the

temperature of a sample and a reference as a function of temperature

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Differential Scanning Calorimeter

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 Conventional DSC
Sample Empty

Metal Metal Metal Metal

1 2 1 2
Sample Reference
Temperature Temperature

Temperature
Difference =
Heat Flow
DSC- Principle:
• DSC is a thermo-analytical 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. 31
Variants of DSC

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Differential Scanning Calorimetry
(DSC)

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Typical DSC Curve

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Transitions in a DSC Curve

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Physical Forms of Solids

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Importance of Solid State Forms in Pharma

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 Differential Scanning Calorimeter

• A DSC consists of a cell, which is the heart of a

DSC.

• The cell is connected with a gas inlet through

which different gases are purged depending on the
data required.

• Based on the DSC cells there are two primary

types: 1. Heat Flux [Link] compensation
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Heat Flux Type DSC

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Power Compensation DSC Cell
Design

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Principles of DSC Analysis

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 Sample Preparation
• Sample Shape

• Sample Pans

• Sample Weight

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 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.
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 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.

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 Sample Pans
• These pans prevent evaporation.

• Two main reasons for the use of these pans are: The
Tg of a polymer or amorphous material shifts with
volatile content.

• Evaporation peaks look just like melting endotherm.

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 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 to be analyzed must be representative of
the total sample and the change in heat flow due to
the transition of interest should be in the range of 0.1
- 10mW

• A recommendation for metal or chemical melting

sample is < 5mg.
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 Sample Weight
• For polymer glass transition 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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 Experimental Conditions
• Start Temperature

• End Temperature

• Reference Pan

• Heating Rate

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 Start Temperature
• Generally, the baseline should have 2 minutes
to completely stabilize prior to the transition of
interest.

• Therefore, at 10°C/min heating rate the run

should start at least 20°C below the transition
onset temperature.

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 End Temperature
• Allowing a 2-minute 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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 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 in the temperature range of interest
should never be used.

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 Heating Rate
• Heating the samples at low heating rates
increases resolution by providing more time at
any temperature.

• Transitions due to kinetic processes (such as

crystallization) are shifted to lower
temperature at highest cooling rates or higher
temperatures at high heating rates.

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 Effects of heating rate
• DSC curves of Acetophenetidin and Phenacetin.

• The Acetophenetidin DSC at 0.5°C/min and

10°C/min showed no effect of heating rate.

• If there were some minor eutectic in this sample

then they would have been detected at the lower
heating rate.

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 DSC curves of Acetophenetidin

02 January 2013 Goa College of Pharmacy, Goa. 54

Effect of Heating Rate

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 Purge Gas
• Nitrogen being a relatively poor thermal
conductor increases sensitivity whereas helium
which is a good conductor of heat to or from
the sample increases resolution.

• DSC is used in studying the melting,

crystallization, glass transition, oxidation and
decomposition of pharmaceuticals.

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Purge Gases

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Summary of DSC experimental
conditions

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Purity by DSC

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Summary of Pharmaceutically Relevant
Information Derived from DSC Analysis

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Melting Point

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Polymorphic Forms

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Pseudopolymorphism

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Amorphous Material

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 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 melting temperature of indium metal is
156.7°C and the observed in calibration is 157.4°C.
• It is 0.7°C high and the instrument values must be
adjusted down to accommodate the true melting
temperature.
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DSC Calibration curve of indium

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 DSC of Polymorphs of Tolbutamide:
Tolbutamide A (Form 1) and B (Form 3)

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SEM of Tolbutamide polymorphs

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 Lactose monohydrate

02 January 2013 Goa College of Pharmacy, Goa. 69

 DSC Applications In
Pharmaceutical Industry
 Characterization - melting point, heat of
fusion, specific heat capacity, water of
crystallization, etc.
 Purity
 Polymorphism
 Screening Tests For Compatibility
 Stability Tests

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 DSC Applications In
Pharmaceutical Industry
 Fast and reliable research tool.
 DSC allows fast evaluation of possible
incompatibilities, because it shows change in the
appearance, shift or disappearance of melting,
endosperms and exotherms or variations in the
corresponding enthalpies of reaction.
 Rapid analysis, easy handling, high significance
for research, development and quality control.

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 Limitations of Thermal Analysis
1) Low sensitivity for transitions involving small
energies.
2) Impurity consisting of molecules of same
size,shape,& character as those of the major
component are not detected by DSC.
3) TGA used to studies hydrates & moisture study
are not always reliable.
4) Thermal analysis are affected by number of
factors
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THANK YOU

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