Applications of DSC

Differential Scanning Calorimetry

PRINCIPLE: It is a technique in which the energy

necessary to establish a zero temp. difference between the sample & reference material is measured as a function of temp. Endothermic reaction: In endothermic reaction more energy needed to maintain zero temp difference between sample & reference. Eg: Melting, Boiling, Sublimation, Vaporization, Desolvation. Exothermic reaction: In exothermic reaction, less energy needed to maintain zero temp difference between sample & reference. Eg: Crystallization, Degradation, Polymerization.

Applications
Determination of Heat Capacity Glass Transition Temperature Crystallization Determination of Melting Point Degree of Crystallinity Detection of impurity Study of polymorphism

Drug excipient compatibility study

Determination of Heat Capacity

When we start heating two pans, the computer will plot the

difference in heat output of the two heaters against temperature that is plot of heat absorbed by the polymer against temperature

 By dividing heat flow (q/t) by the heating rate (T/t). It ends up

with heat supplied divided by the temperature increase, which is called heat capacity.

When a certain amount of heat is transferred to the sample, its

temperature increases by a certain amount, and the amount of heat it takes to get a certain temperature increase is called the heat capacity or Cp .

Glass Transition Temperature (Tg)

The Tg is the reversible change from a glassy to rubbery state & vice-versa DSC detects Tgs by a step change in Cp On further heating the polymer to a certain temperature, plot will shift downward suddenly, like this:

Crystallization
After glass transition, the polymers have a lot of mobility. When they reach the right temperature, they will give off enough energy to move into very ordered arrangements, which is called crystals.
The temperature at the highest point in the peak is usually considered to be the polymer's crystallization temperature, or Tc

 Also, we can measure the area of the peak, which tells us the latent energy of crystallization of the polymer

But most importantly, this peak tells us that the polymer can in fact crystallize
If you analyze a 100% amorphous polymer, like

polystrene, you wouldn't get this peak, because such materials don't crystallize

Melting Point
When we reach the polymer's melting temperature, Tm the polymer

crystals begin to fall apart, that is they melt. It comes out of their ordered arrangements, and begin to move around freely that can be spotted on a DSC plot

Degree of Crystallinity
DSC can also tell us how much of a polymer is crystalline and

how much is amorphous? If we know the latent heat of melting, Hm, we can figure out the answer.

Where, mc is the total amount of grams of polymer that were

crystalline below the Tc, mtotal is weight of the sample

Determination of Purity
A sharp melting endotherm indicates the relative purity where as broad asymmetric curve suggest impurity. The presence of minute amount of substance (impurity) broadens its melting range & lowers its mp.

Compare to other thermal methods, DSC is best method for detection of impurity.

Polymorphs Determination
The

all thermodynamic parameter in the polymorphism substance is different like melting, sublimation temperature, kinetics, stability, solubility, heat capacity, crystal hardness & shape which are extremely important for the dosages form. During preformulation, it is important to identify the polymorph that are stable & also important to determine whether polymorphic transition are possible within the temperature range used for stability studies, processing (drying, milling, mixing, granulation etc.) & storage.

 Example: Mannitol occurs in four forms, all melting at the same temp. & they are non hygroscopic, only form B shows a small endotherm exotherm process.

Drug-Excipient Compatibility study

o DSC is widely used to investigate and predict any

physico-chemical interaction between drug and excipients involving thermal changes. o METHOD -The preformulation screening of drug-excipient interaction requires (1:1) Drug:excipient ratio, to maximize the likehood of observing an interaction. -Mixture should be examined under N2 to eliminate oxidative and pyrrolytic effects at heating rate ( 2, 5 or 100c / min) on DSC apparatus.

Example: DSC of Ofloxacin Tablets

Graph 1 of figure shows peak at 278.330c. (melting endothermic peak of Ofloxacin). Graph 3 (Physical mixture of Ofloxacin & Lactose) shows absence of peak at 278.330c and slight pre shift in Lactose peaks. DSC RESULT-- INCOMPATIBLE