THERMAL ANALYSIS

Dr.rer.nat. Endang Lukitaningsih, M.Si., Apt

Surabaya, 26 April 2007
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http://www.youtube.com/watch?NR=1&v=r-

pEb60ZON4&feature=endscreen

EQUIPMENT:
Two basic types of Differential Scanning
Calorimetry (DSC) must be distinguished:
1. The heat flux DSC
2. The power compensation DSC.
Differential Scanning Calorimetry (DSC)
measures the change of the difference in the
heat flow rate to the material (sample) and to a
reference material while they are subjected to
controlled temperature program.
The sample and reference are placed in
identical environments, metal pans on
individual bases each of which contain a
platinum resistance thermometer (or
thermocouple) and a heater.
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PRINCIPLE OF MEASUREMENT:

in DSC, the measuring principle is to compare the

rate of heat flow to the sample and to an inert

material which are heated or cooled at the same rate.
Changes in the sample that are associated with
absorption or evolution of heat cause a change in the
differential heat flow which is then recorded as a
peak.

The area under the peak is directly proportional to the
enthalpic change and its direction indicates whether
the thermal event is endothermic or exothermic.

Reference materials in DSC

EXAMPLE OF DSC THERMOGRAM

Y axis : heat flow (mW)
X axis : temperature (C)

The amount of energy which has to be supplied to or withdrawn from the sample to
maintain zero temperature differential between the sample and the reference is the
experimental parameter displayed as the ordinate of the thermal analysis curve.

H = KA
where H is the enthalpy of transition, K is the calorimetric constant (vary from instrument to
instrument), and A is the area under the curve.

APPLICATION OF DSC
Purity determination using DSC

Types of impurity

Organic impurities (process and drug related)

Inorganic impurities

Residual solvents

Organic impurities

Can arise during manufacturing process and/or storage

Volatile or nonvolatile

Identified or unidentified

Include: starting materials; by products; intermediate; degradation
product; reagents; ligands and catalysts

Inorganic impurities

Resulted from the manufacturing process

Include: reagents, ligands and catalysts; heavy metals; inorganic
salts
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Purity determination

Purity determination

When a compound is observed to melt without

decomposition, the vant Hoff equation can be applied

Ts = T0 {R(T0)2.Xi}/{FHf}

Ts : sample temperature
T0 : melting point of the pure major component
Xi : mole fraction of the impurity
F : fraction of solid melted coresponding to Ts
Hf : enthalpy of fusion of the pure component

A plot of Ts against 1/F should yield a straight line, whose

slope is proportional to Xi

Purity determination

The vant Hoff plot showing a DSC purity calculation

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Purity determination using DSC..

ICH (The International Conference on

Harmonisation):
Impurities must be below the 0,1%
unless the potential impurities are
expected to be unusually potent or
toxic

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APPLICATION OF DSC..
Study of transition process from solid to liquid
phase

H of fusion

H of crystallization

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CYCLICAL DIFFERENTIAL SCANNING

CALORIMETRY

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CYCLICAL DSC

Heating and cooling curve of seven lots of

microcrystalline wax obtained from the same supplier.
All of the lots exhibited similar endothermic events at
approximately 65 and 88C

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CYCLICAL DSC
Formation of metastable acetaminophen:
Acetaminophen

Wax
Heated at 80 5 C

Suspension of Acetaminophen in wax

Allowed to cool

Spray the atomized onto cooled air

Filtration

CRYSTAL (1)
CRYSTAL (2)

FILTRATE
Heated at 100-110C
Cooled

CRYSTAL (3)

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CYCLICAL DSC
Formation of metastable acetaminophen:

The melting point shifted

approximately 10C

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APPLICATION DSC IN STUDIES OF

POLYMORPHISM

Polymorphism :

The ability of the same chemical substance to exist in

different crystalline structures that have the same empirical
composition
The systems are often distingushed on the basis of the type
of interconversion between the different forms
(thermodynamic), being classified as either enantiotropic or
monotropic
Enantiotropic..convertion between the two polymorphs on
heating and cooling may be reversible
Monotropic transition from one polymorph to another will
be irreversible
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Enantiotropic example

DSC thermogram of ibuprofen lysinate over the

temperature range 20 - 200C

DSC thermogram of ibuprofen lysinate over the

temperature range 25 - 75C

ENANTIOTROPIC
They have the same endothermic transition at about 64C

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Monotropic example

46,6C

DSC thermogram of Tristearin

Upper: The nature of tristearin solid system has
melting point at 58,2C.
Lower: DSC thermogram after quench cooled from
120 to -20C in less than 5 min.

DSC thermogram of Tristearin that slowly cooled

from 120 to -20C over two-days time period. There
is three part pattern, but the ratio of lower melting
metastable form to higher melting stable form is
greatly shifted
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MONOTROPIC

Study of phase transformation associated

with the compression

These changes in thermal profile were traced to a pressureinduced polymorphic transition of one of the excipient in the
formulation

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TERIMAKASIH, SEMOGA BERMANFAAT