Operation and Application of Differential Scanning Calorimetry (DSC) in Pharmaceuticals

OPERATION AND APPLICATION
OF DIFFERENTIAL SCANNING
CALORIMETRY (DSC) IN
PHARMACEUTICALS
Presented By,
Md. Tayfuzzaman
MS in Applied Chemistry & Chemical Engineering, University of Dhaka
Senior Executive, Analytical Research & Development
Square Pharmaceuticals Limited
Defination
Differential Scanning Calorimetry, or DSC, is a
thermal analysis technique that looks at how a
material’s heat capacity (Cp) is changed by
temperature. A sample of known mass is heated
or cooled and the changes in its heat capacity are
tracked as changes in the heat flow.
Inventors
The technique was developed by E.S. Watson and M.J.
O'Neill in 1962, and introduced commercially at the
1963 in Pittsburgh Conference on Analytical Chemistry
and Applied Chemistry.
Instrumental Design
Prerequisite and Precautions of Operation
Check the Nitrogen gas pressure, minimum pressure
requirement is 2 bar.
Keep the chiller switched on through out the operation.
Always put-on the sample-cover of DSC during operation.
Take care during sample preparation for uniform sealing of

pan & cover.
Basic Operational Procedure
 Check the machine is clean and calibrated.
 Switch on the valve of N2 Gas, Chiller, Computer and Printer.
 Take 2-5 mg (or as required) of sample previously weighted in a microbalance and
place in an aluminum or copper pan dedicated for DSC analysis
 Place the cover and crimp properly and in the same way prepare a blank.
 Put both the sample and blank in the respective position of the Heat sink.
 Open the respective software and set initial & final temperature, Heating rate etc.
 Input sample information and sample weight in the respective field.
 Run the instrument and go to the running view to observe the acquired thermogram.
 After completion of the acquisition, open the data and process as per requirement.
General Application parameters
Tm
Tg TC
Specific heat
capacity Applicat ΔH
ion
Reaction Kinetics Polymorphism
Glass transition temperature (Tg)
Glass transition temperature (Tg) is defined as the
temperature at which the mechanical properties of a
polymer radically changed due to the internal
movement of the polymer chains.
Melting Temperature (Tm)
Melting temperature may refer to the temperature at which a substance
changes from solid to liquid state.
Crystallization Temperature (Tc)
Crystallization is a chemical solid–liquid separation technique, in which mass
transfer of a solute from the liquid solution to a pure solid crystalline phase
occurs.
Crystallization of polymers is a process associated with partial alignment
of their molecular chains. Polymers can crystallize upon cooling from the
melt
Enthalpy Change (ΔH)
Enthalpy (H) is a measurement of energy in a thermodynamic system. It is the
thermodynamic quantity equivalent to the total heat content of a system. It is equal to the
internal energy of the system plus the product of pressure and volume. i. e. H=U+PV
The total enthalpy of a system cannot be measured directly, the enthalpy change of a

system is measured instead. Enthalpy change is defined by the following equation:
ΔH =Hf -Hi
where
ΔH is the "enthalpy change",
Hf is the final enthalpy of the system
Hi is the initial enthalpy of the system
Thermogram for enthalpy Change
Polymorphism
By DSC we can easily determine the polymorphic state of a pure molecule
as well as composite. Based on the thermodynamic nature we can
define the crystalline and amorphous state. Here some limitations to
determine the specific form of a crystalline state. To determine the
same XRD is an efficient scientific tool.
When a crystalline molecule is heated in a specific condition, melted to
liquid form and crystallize from the melt after withdrawing the heat.
Here a certain amount of energy is released as crystallization enthalpy.
In case of amorphous molecule, solidification is occurred directly
without losing energy.
That’s why scientists are defined the amorphous state as configurationaly
modified liquid.
Typical Thermogram for Crystalline molecule
Typical Thermogram for Amorphous molecule
Mode of reaction and Kinetics
By DSC easily we can determine the thermal mode of reaction i.e.
exothermic or endothermic.
Kinetic equations of decomposition can be developed
based on experimental data obtained from various thermal
analysis methods, such as thermogravimetry, differential
thermal analysis, differential scanning calorimetry (DSC)
Methods based on isothermal DSC runs at different temperatures. The
utilization of the partial areas under one DSC curve to transform the data
into degree of conversion. The reaction mechanism and the type of kinetic
equation are then determined at each temperature using various kinetic
methods. Rate constants at all experimental temperatures are calculated.
Specific Heat Capacity (Cp)
Heat capacity is the amount of heat required to raise the
temperature of a material by 1°C from T1 to T2
True Heat Capacity (no transition) is completely reversible;
the material releases the same amount of heat as
temperature is lowered from T2 to T1
Application in Pharmaceutical Practices
Melting point and Glass transition for plastic primary
packaging materials
Drug-Excipients compatibility study
Determination of additives in polymers
 Solid state stability of Drug substances (Specific
polymorphic form) in drug product.
Drug-Excipients compatibility study
 Incompatibility between drugs and excipients can alter
drug stability and bioavailability and thereby affect their
safety and efficacy. Study of drug-excipient compatibility is
an important process in the early development stage of
stable solid dosage forms. Differential scanning calorimetry
(DSC) is widely used for evaluating the drug-excipient
interaction.
Generally binary mixtures of API and each excipients is
kept under stress condition (e. g. 50 Cand 75%RH for at
least 15 days)
Drug-Excipients compatibility study
 Melting point and Enthalpy change for the controlled API
as well as the binary mixtures were recorded by the DSC.
 Melting point: If the melting point of the binary mixture
shifted from the controlled API it not compatible.
 ΔH: Due to the interaction with excipients the API can easily
depredated due to the lowering of required enthalpy for
melting.
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OPERATION AND APPLICATION

Keep the chiller switched on through out the operation.

Always put-on the sample-cover of DSC during operation.

Take care during sample preparation for uniform sealing of

The total enthalpy of a system cannot be measured directly, the enthalpy change of a

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