ADVANCED INSTRUMENTAL

ANALYSIS
Shashidhar M
Department of Pharmaceutical Analysis
ADVANCED INSTRUMENTAL ANALYSIS
Contents

• Introduction Thermal Analysis

• History od DSC
• Principle of DSC
• Instrumentation
• Typical DSC curve
• Application
• Factors affecting DSC curve
• Advantages
• Disadvantages
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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.
• 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
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Common Thermal Analysis Methods and the Properties Measured
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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.
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Principle of DSC

• 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.
OR
• It is a technique in which the energy necessary to establish
a zero temperature difference between the sample &
reference material is measured as a function of
temperature.
• 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.
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During heating two types of reactions can be take place one is

the endothermic and the other is the exothermic.
• 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.
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Instrumentation
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Types of DSC

There are two different types of DSC instrument

• Heat flux DSC
• Power compensated DSC

Heat Flux DSC power compensation DSC

ADVANCED INSTRUMENTAL ANALYSIS
Heat flux DSC

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.
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• 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.
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Power compensated DSC

Power compensated 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.
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• 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. 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
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Typical DSC curve
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• 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
• 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,
A is the area under the curve
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Applications

• Specific heat capacity

• Glass transitions
• Melting and boiling points
• Crystallization time and temperature
• Percent crystallinity
• Heats of fusion and reactions
• Oxidative/ Thermal stability
• Rate and degree of cure
• Reaction kinetics
• Purity
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Heat capacity
The heat flow is heat (q) supplied per unit time (t), whereas,
The heating rate is temperature increase (ΔT) per unit time (t),
Heat flow= heat/ time = q/t
Heating rate = temperature increase / time = ΔT / t
By dividing heat flow (q/t) by the heating rate (ΔT/t), It ends
up with heat supplied divided by the temperature increase,
which is called heat capacity.
(q/t ) / (ΔT / t) = q/ ΔT= Cp = heat capacity
Or
Cp = q/ ΔT
ADVANCED INSTRUMENTAL ANALYSIS

Glass transition
On further heating the polymer to a certain temperature,
plot will shift downward suddenly
This means there is more heat flow. There is an increase in
the heat capacity of the polymer. This happens because the
polymer has just gone through the glass transition
(It is a reversible transition in amorphous material from a
hard, brittle state into molten rubber like state).Because of
this change in heat capacity that occurs at the glass
transition, we can use DSC to measure a polymer's glass
transition temperature.
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Crystallization
After glass transition, the polymers have a lot of
mobility and never stay in one position for very long
time. But when they reach the right temperature,
they will give off enough energy to move into very
ordered arrangements, which are called crystals.
When polymers fall into these crystalline
arrangements, they give off heat. So it doesn't have to
put out much heat to keep the temperature of the
sample pan rising. This drop in the heat flow as a big
peak in the plot of heat flow vs. temperature.
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Melting
If polymer is heated past its Tc, it reaches another
thermal transition, called melting. When polymer's
melting temperature is reached, Tm, the polymer
crystals begin to fall apart, that is they melt. The heat
which polymer give off when crystallized is absorbed
when reached at Tm. The heater under the sample
pan puts a lot of heat into the polymer in order melt
the crystals and keep the temperature rising at the
same rate as that of the reference pan. This extra heat
flow during melting shows up as a big dip on DSC plot
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Purity
DSC provides a rapid yet reliable method for determining the
purity of materials, particularly pharmaceuticals. The
presence of minor impurities may reduce the effectiveness of
the drug or even cause adverse side effects on the patient.
The purity is readily calculated from DSC curve of a single
melting event of a few milligrams of the substance, without
the need for reference standard of drug substances.
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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
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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
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Advantages

• It is a fast technique, i.e., it takes a small time to perform

one run.
• Different kind of samples such as solid, liquid, powders,
thin films can be tested in a variety of environments (air,
vacuum, inert gas, etc.)
• A wide range of temperature can be used to analyse the
phase transitions in a material, and quantitative analysis of
these transitions can be done easily using softwares.
• The applicability of DSC can be extended to a wide variety
of materials that includes the pharmaceutical and drug
industry, polymers, liquid crystals, and food science. DSC
can also be used to determine the oxidative stability of a
material.
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Disadvantages

• In case of overlapping processes, it measures only the

average value of heat flow. The difficulty to separate
multiple events make further analysis complicated.
• The sensitivity and resolution of DSC cannot be improved
simultaneously. In case of processes like transitions having
low energy, sensitivity can be increased by increasing
sample size or heating rate. But this, in turn decreases the
resolution.
• Further, the sensitivity of the measurements also depend
upon the laboratory conditions (temperature, humidity,
etc.) and the cooling process. Due to this small transitions
like glass transition are difficult to detect.
THANK YOU
Shashidhar M
Department of Pharmaceutical Analysis