Differential Scanning Calorimetry(DSC)

The general instrumentation for the thermal analysis primarily includes:

i. A sample holder, where the sample is kept

ii. Sensors for detecting the required properties with respect to temperature
iii. A closed chamber where the sample and sensors can be placed, and the experimental
parameters can be controlled according to the requirements.
iv. A computer for adjusting the experimental parameters, collecting data and performing
further calculations

One of the most common thermo-analytical technique is “Differential Scanning Calorimetry”

(DSC). E.S. Watson and M.J. O'Neill developed this technique in 1962 and commercialized it in
1963 at the Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. The
transitions associated with the change in temperature are referred to as thermal transitions. DSC
provides useful information about the thermal transitions occurring in a sample. It is a very
informative tool for studying the phase changes taking place in an amorphous material as a
function of temperature. Basic phase changes occurring in an amorphous material when it is heated
are:

a) Glass transition: It is a reversible phase change that involves change in the structure of an
amorphous material form a relatively hard state to a rubbery state. Knowledge of the temperature
at which glass transition occurs (known as “glass transition temperature”) is of great significance
as it gives information about the stability of the glassy or amorphous state.

b) Crystallization: It is an irreversible phase change that involves the ordering of the disordered
structure through nucleation and growth processes, thereby forming crystalline structure.

c) Melting: It is a phase change in which the crystalline lattice breaks into a disordered state (solid
to liquid transition → “fusion”). It is single step endothermic process, unlike crystallization which
is a two-step, exothermic process (nucleation and growth).

d) Curing: Curing of a polymer occurs when individual chains form strong bonds to other chains,
a process that is sometimes referred to as “crosslinking.” Like crystallization, this process of chain
ordering and bond formation is exothermic. The curing temperature is generally given as the onset
of the curing peak on the DSC curve.

Differential Scanning Calorimetry (DSC) relies on the measurement of the difference between the
heat flow vs. temperature relation of the sample and the heat flow vs. temperature relation of a
standard.

Differential scanning calorimetry (DSC) is an effective analytical tool to characterize the physical
properties of a polymer. DSC enables determination of melting, crystallization, and mesomorphic
transition temperatures, and the corresponding enthalpy and entropy changes, and characterization
of glass transition and other effects that show either changes in heat capacity or a latent heat

DSC measures the amount of heat required to raise the temperature of sample, with respect to
reference, as a function of temperature. In other words, it provides information about the exo and
endo-thermic processes occurring in sample by measuring the amount of heat absorbed or released
during heating or cooling of the sample. It provides information about the characteristic
temperatures of a sample like the glass transition temperature, crystallization and melting
temperatures, heat of phase changes such as fusion and melting, heat capacity, etc.

Among the differential scanning calorimeters, two types of devices should be specified:

 flow (heat flux DSC),

 compensation (power compensation DSC).

They differ in their construction and working. Heat flux DSC allows the temperature difference
between the sample and reference to vary and this temperature difference is used to get required
heat flow. In heat flux differential scanning calorimeters, directly measured signal is a change in
temperature between a test sample and a reference sample. This difference is proportional to the
flow of the heat flux between the two samples and is automatically converted to the value of the
heat flux using special software.
Compensating differential scanning calorimeters consist of two identical and isolated heaters
located in the same temperature (in one heater a tested sample is placed and in the other - a
reference sample). Temperature changes during the phase transformation or the reaction in the
sample are compensated by varying the electrical energy supplied to the heater which is directly
proportional to the heat absorbed during the process. The furnace of a power compensated DSC
uses two separate blocks for sample and reference, whereas a heat flux DSC has a single block for
heating both sample and reference. Power compensated DSC works on the principle of keeping
the temperature difference between sample and reference constant. The amount of heat flow to be
supplied to the sample and reference is determined by the differential thermal power between them.
Power compensated DSC have better resolution of thermal events occurring during heating of a
sample, whereas heat flux DSC is more sensitive towards the thermal events.
The sample and reference both are kept adjacent to each other and a common heating profile is
applied to both. Both are sealed in aluminium pans (or copper). Reference is commonly an inert
material like alumina, or an empty pan with lid. The crucibles used are made up of platinum,
aluminium, copper, gold, etc., in order to withstand with the high temperatures applied to them
and to avoid any reaction with them. Different atmospheres, such as air, nitrogen, argon, vacuum,
etc, can be maintained in order to achieve desired outcome. Both (sample and reference) are
connected to a temperature sensor and a heater coil. Heater coil heats them at a constant rate and
temperature sensor senses the temperature difference between the sample and reference. Same
Linear heating rate is applied to both, i.e., temperature is increased at a constant rate. Both the
sample and reference are maintained at same temperature. When the heating is carried out, the
sample tends to release or absorb heat as a result of phase changes occurring in it. In order to
maintain same temperature for both sample and reference, heat is needed to be supplied to the
sample undergoing phase transitions. This amount of heat supplied or taken out determines the
exo- or endo-thermic processes occurring in the sample. The amount of heat transferred to the
sample is monitored using a PC and the output is received in form of a thermo-gram showing
different exothermic and endothermic peaks. Two different conventions are used to represent the
exo- and endo thermic processes. Exothermic and endothermic reactions are shown in positive and
negative directions respectively, or vice-versa depending upon the kind of conventions used in the
instrument. The thermogram can be used to understand many important properties of a material,
such as heat capacity, temperature and enthalpy of phase changes such as glass transition,
crystallization, and melting.

The result of calorimetric measurements is a DSC curve shown as the temperature/time

dependence on the heat flux (per time unit). An endo- and exothermic peaks are recorded on these
curves, which result from the temperature differences between a tested sample and a reference
sample, showing negative or positive deviations from the so called “baseline”, which is recorded
at the time when no transformations/reactions occurs in the sample. The differences are caused by
phase transformations and chemical reactions occurring in the material. If the temperature of a
tested sample during the phase transformation/chemical reaction is lower than the reference
temperature, the heat is absorbed. The situation is registered as the endothermic peak. Conversely,
when the sample temperature is higher and there is separation of the heat, then this is marked as
the exothermic effect on the DSC curve.

Sometimes, TGA and DSC are used simultaneously, since they require same experimental
conditions for their operation. This concurrent use of two instruments is known as simultaneous
thermal analysis (STA). Apart from controlling temperature profile, it is very important to control
other parameters such as atmosphere inside the chamber. Some reactions need inert atmosphere,
whereas others can be done in air also. Depending upon the reaction; air, nitrogen, or helium
atmospheres can be used in the instruments.

Pharmaceutical Applications

DSC is used to study phase transitions such as melting and exothermic decompositions, and glass
transitions. In these experiments, molecules change from one conformation to another. It also
establishes specific temperature points termed thermal transition temperatures or melting points
for samples in solid, suspended or dissolved form. It is used as an industrial quality control
technique as it can establish sample purity and detect the presence of impurity in a drug
formulation, for instance. It gives a wealth of information regarding both the physical and energy
properties of the substance.

Characterization of drugs

The pharmaceutical industry needs to have drugs which have been precisely characterized for the
purpose of accurately defining the parameters of production. This includes knowing at what
temperature undesirable phase changes will occur, for instance, crystallization of a drug. The
conditions can then be adjusted to produce the desired phase, e.g. the amorphous powder form.

Nanosolids
The use of nanosolids in pharmaceutical formulations is also becoming a big development,
although intensive research into their properties is required. Their quantification in drugs has
depended upon DSC which can measure the amount of the amorphous or crystalline phase of these
molecules. This helps to monitor the way these compounds behave under experimental conditions
which will determine the regulatory framework of manufacturing processes.
Nanostructured lipid carriers and solid lipid nanoparticles are also being studied as potential
carriers in drug delivery, which could be of the greatest use in various therapeutic applications.
These nanospheres seem to be capable of delivering drugs with greater effect, achieving better
tolerance and biodegradability, being more bioavailable, and crossing the blood-brain barrier to
specifically target the brain tissues.

The solid nanoparticles can be used to develop emulsions, control the rate and site of drug delivery,
and form liposomes as well as coat the active drug against biochemical denaturation or breakdown.
Moreover, it is possible to develop an industrial cycle to produce these particles on a large scale.
The disadvantages of this formulation include drug expulsion and reduced drug entrapment
efficiency, both of which can be overcome by different methods of nanoparticle crystal formation.
Thermal analysis of these structures is carried out using DSC.

Solid-state drug formulations

Solid-state analysis is responsible for most of the suitability of DSC in pharmaceutical research.
Crystalline solids and polymorphic forms can be characterized, detected and identified. DSC is
especially important in the study of solid dispersions and polymers which are being increasingly
used in drug formulations.

Another use is in research on lyophilization, as well as studies of solid-state drug kinetics. This
helps to understand how drugs become more or less stable under various conditions. Accelerated
storage conditions may be simulated followed by DSC of samples to detect drug recrystallization
after extrusion as amorphous drug.