DSC: PRINCIPLE, APPLICTION AND INTERPRETATIONP R E S E N T E D B Y: R A H U L K U M A R

M . P H A R M A

B I T S P I L A N I

R A J A S T H A N

CONTENTSIntroduction

Types/ Modifications

Application

Sample Preparation

Calibration

Interpretation

References

INTRODUCTIONThermal analytical methods have become important tools for the development of modern medicines.

These instruments provide quantitative information about exothermic, endothermic and heat capacity changes as a function of temperature and time (such as melting, purity and glass transition temperature).

Differential scanning calorimetry instruments are primarily used in the earliest stages of drug development, where experiments are often of an exploratory nature

TYPES OF TAHRMAL ANALYSISIt includes – DTA, DSC

DSC is further categorized as :

Power-compensated DSC

Heat flux DSC

a)DTA b) PC DSC c) HF DSC

Application

•Glass transitions

•Melting and boiling points

•Crystallization time and temperature

•Percent crystallinity

•Heats of fusion and reactions

•Specific heat capacity

•Oxidative/thermal stability

•Rate and degree of cure

•Reaction kinetics

•Purity

Sample Preparation

DSC samples are analyzed in small metal pans, designed for optimal thermal conductivity and

minimum reaction with the samples (for example, aluminium alloy, platinum, stainless steel and silver).

Pans may be open, pin-hole, covered or sealed

For accurate quantitative work the thermal mass of the sample and reference pans

should be matched.

Sample sizes of 3–5 mg, sometimes with less than 1 mg optimum result may be obtain

CalibrationTo ensure expected working condition and accurate results.

Calibration AccessoriesMicron Balance

Crucible sealing press

Crucible (2) : sample and reference 40 microliter

Calibration toolbox

Calibration material

Calibration Process

Calibration standards have classically been metals such as indium, tin, bismuth and

lead.

Separate calibration is required at each scan rate used

Interpretation: Exothermic Transition -Up

Endothermic Transition -DownDifferential scanning calorimetry scan of sucrose (undried), showing the glass transition temperature, (Tg), recrystallization exothermtemperature (Tc) and enthalpy (DHc), melting endotherm temperature (Tm) and enthalpy (DHf) and onset of degradation 10K /min. Endothermic transitions are down

Melting PointWhere To is onset temperature of melting, Te is the extrapolated onset melting temperature,enthalpy of fusion (⌂Ho), Tm is peak melting temperature

Purity

Ts = Te – RTe 2X

ΔHoF

Van’t Hoff eq.

A streight line relationship is expected between Ts and 1/F for pure compound.

where Ts is the sample temperature at equilibrium (K),

Te is the melting temperature of the pure component (K),

R is the gas constant (8.314 J/mol/K),

X is the molar fraction of the impurity,

ΔHo is the enthalpy of fusion of the pure compound (J/mol) and

F is the fraction of the sample molten at Ts.

Polymorphism

CRYSTALLINE OR AMORPHOUS COMPOUND ?

Regulatory issuesThe use of DSC for the determination of transition temperatures and sample purity is described in the United States Pharmacopeia.

It is stated that detailed records should be kept of all experimental parameters, and that special attention be given to the number of significant figures reported in the results.

The patent or regulatory status of newly discovered drug forms may depend on the quality of the DSC maintenance and calibration records.

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