Experimental Parameters of Differential Scanning Calorimetry (DSC)

1. Presented By – Gyanendra Kumar Prajapati
1st year M.Pharm
KLE University’s College of Pharmacy,
Bengaluru
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2. 1. Sample Preparation
2. Experimental Condition
3. Calibration
4. Heating and Cooling Rates
5. Sources of Errors
6. Advantage & Disadvantage
7. Pharmaceutical Applications
8. References
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3.  Accurately-weighed (3-20 mg, usually 3-5 mg for simple
powders)
 Small sample pans (0.1ml) of inert or treated metals
(Al,Pt,stainless)
 Several pan configurations ,e.g.; open ,pinhole, or
hermetically- sealed pans
 Some material and configuration should be used for the
sample reference.
 Material should completely cover the bottom of the pan
to ensure good thermal contact.
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4.  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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5.  Sample Shape
 Sample Pans
 Sample Weight
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6.  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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7.  In most cases lids 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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8.  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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9.  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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10.  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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11.  For polymer glass transition 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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12.  Start Temperature
 End Temperature
 Reference Pan
 Heating Rate
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13.  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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14.  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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15.  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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16.  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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18.  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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21.  DSC curves of Acetophenetidin.
 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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23.  If you use multiple heating rates then start with 1.0 and
10°C/min.
 Melting is a thermodynamic process and the onset of
melting does not change significantly with heating rate.
 Evaporation, dissolution and decomposition are kinetic
processes that will move to higher temperatures as
heating rate increases.
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24. • Calibration
• Contamination
• Sample preparation – how sample is loaded into a pan
• Residual solvents and moisture.
• Thermal lag
• Heating/Cooling rates
• Sample mass
• Processing errors.
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25. • Instruments can be used at very high temperatures
• Instruments are highly sensitive
• Flexibility in sample volume/form
• Characteristic transition or reaction temperatures can be
determined
• High resolution obtained
• High sensitivity
• Stability of the material.
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26. • DSC generally unsuitable for two-phase mixtures
• Difficulties in test cell preparation in avoiding
evaporation of volatile Solvents
• DSC is generally only used for thermal screening of
isolated intermediates and products
• Does not detect gas generation
• Uncertainty of heats of fusion and transition
temperatures.
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27.  Glass Transition Temperature (Tg)
 Glass Transition Size (ΔCp)
 Crystallization temperature (Tc)
 Crystallinity (based on J/g and adjusted to %)
 Polymorphic Transitions.
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28.  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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29.  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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30.  Principles of Instrumental Analysis – Skoog , Holler And
Crouch.
 Thermal Methods – Dodd And Tonge, Wiley Series.
 B.K.Sharma, Instrumental Method of Chemical Analysis,
Thermoanalytical methods, 26th edition.
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