Different types of Thermal Techniques and its applications

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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