thermal analysis

DIFFERENTIAL SCANNING CALORIMETRY

INTRODUCTION:

THERMAL ANALYSIS: A number of physical and chemical effects can be produced

by temperature changes, and methods for characterizing these alterations upon heating or

cooling a sample material are referred to as thermal analysis.

The physical and chemical changes a sample undergoes when heated, are characteristic of the

material being examined. By measuring the temperature at which such reactions occur and

the heat involved in the reaction, the compounds present in the material can be characterized.

The majority of known inorganic compounds have been so characterized. The physical and

chemical changes that take place when unknown sample is heated provide the information

that enables the identification of the material. These changes also indicate the temperature at

which the material in question ceases to be stable under normal conditions.

Common methods of thermal analysis are DSC, DTA, TGA, and TMA.

THERMAL ANALYTICAL METHODS:

S

no

Name of the technique Instrument

employed

Parameter

measured

Graph

1 Thermogravimetry (TG) Thermobalance Mass Mass vs

temperature

2 Derivative

thermogravimetry

(DTG)

Thermobalance dm/dt dm/dt vs time

3 Differential thermal

analysis (DTA)

DTA apparatus ∆T ∆T vs temperature

4 Differential scanning

calorimetry (DSC)

Differential scanning

calorimeter

dH/dt dH/dt vs

temperature

5 Thermometric titrimetry Calorimeter Temperature Temperature vs

titrant volume

6 Dynamic reflectance

spectroscopy (DRS)

spectrophotometer Reflectance % reflectance vs

temperature

7 Evolved gas detection

(EGD)

Thermal

conductivity cell

Thermal

conductivity(TC)

TC vs

temperature

8 Dilatometry (TMA) Dilatometer Volume or length Volume or length

vs temperature

K.Sravya, pharmaceutics, NCOP


9 Electrical conductivity

(EC)

Electrometer or

Bridget

Current(I) or

Resistance(R)

I or R vs

temperature

10 Emanation thermal

analysis (ETA)

ETA apparatus Radioactivity (E) E vs temperature

THERMAL EVENTS:

A(s1) A(s2) phase transition

A(l) melting

A(g) sublimation

B(s) + gases decomposition

gases

A (glass) A (rubber) glass transition

A(s) + B(g) C(s) oxidation, tarnishing

A(s) + B(g) gases combustion, volatilization

A(s) + (gases)1 A(s) + (gases)2 heterogeneous catalysis

A(s) + B(s) AB(s) addition

AB(s) + CD(s) AD(s) + CB(s) double decomposition

WHERE DO WE USE IT ???

Virtually every area of modern Science and Technology.

The basic information obtained is needed for the research and development of new

products.

Increasing use for quality control and assurance

In academia from basic undergraduate studies to the most sophisticated postgraduate

research.


Calorimetry: The study of heat transfer during physical and chemical process.

Calorimeter: A device for measuring the heat transferred.

Differential scanning calorimetry (DSC) is a technique for measuring the energy

necessary to establish a nearly zero temperature difference between a substance and



an inert reference material, as the two specimens are subjected to identical

temperature regimes in an environment heated or cooled at a controlled rate.

It is the most widely used method of thermal analysis in pharmaceutical field.

Thus, when an endothermic transition occurs, the energy absorbed by the sample is

compensated by an increased energy input into the sample inorder to maintain a zero

temperature difference.

Because this energy input is precisely equivalent magnitude of energy absorbed in

transition, direct calorimetric measurement of transition is obtained from this

balancing energy.

On the DSC chart recording, the abscissa indicates the transition temperature and the

peak measures the total energy transfer to or from the sample.

WHAT DOES DSC MEASURE?

DSC measures the amount of energy (heat) absorbed or released by a sample as it is heated,

cooled or held at constant temperature. DSC also performs precise temperature

measurements. DSC IS USED TO ANALYZE?

Melting point

Crystallization

Glass Transition

O.I.T. (Oxidative Induction Time):

It is a standardized test performed in DSC that measures the level of stabilization of the

material tested. The time between melting and onset of decomposition in isothermal

conditions is measured.

Polymorphism

Purity

Specific Heat

Kinetic Studies

Curing Reactions:

The process in which an adhesive undergoes a chemical reaction and becomes a solid by

forming a bonded joint. The reaction may be initiated by heat, light, UV radiation, water etc.

Denaturation:



A process pertaining to change in the structure of a protein from regular to irregular

arrangement of polypeptide chains.

WHERE MOSTLY USED ?

Pharmaceutical industry

To find the Purity of the compounds.

Food industry

For Characterization of fats and oils

Polymer industry

To find the Synthetic blends

DSC IN PHARMACEUTICAL INDUSTRY:

Purity determination of sample directly

Detection of polymorphism

Quantification of polymorph

Detection of metastable polymorph

Detection of isomerism

Stability/ compatibility studies

Percentage crystallinity determination

Lyophilization studies

Lipid/ Protein determination

Finger printing of wax

Amorphous content in excipient

Choosing better solvent

DSC is most often used thermal analysis method, primarily because of its speed, simplicity

and availability.

PRINCIPLE:

The difference in heat supplied to the sample, and the reference material per unit time

is recorded and plotted as dH/dt vs the average temperature to which the sample and

reference to be raised.

COVENTIONAL DSC:



In general an endothermic reaction on a DSC arises from

1) Desolvations

2) Melting

3) Glass transitions and

4) Decompositions.

An exothermic reaction measured by DSC is usually indicative of molecular reorganizations

such as

1) Crystallization

2) Curing

3) Oxidation

The differential heat input is recorded with a sensitivity of +0.1 millicalories per second and

the temperature range over which the instrument operates is -1750c to 7250c.



The heat flow may be of two types:

1) Relative heat flow:

Measured by many DSC instruments.

2) Absolute heat flow:

Used by TA Q 1000 type instruments. Dividing the signal by measured heating rate

converts the heat flow signal into a heat capacity signal.



OUTPUT OF DSC:

Glass Transition

Step in thermogram

Transition from disordered solid to liquid

Observed in glassy solids, e.g., polymers

Tg, glass transition temperature

Temperature, K

Thermogram

dH

/dt

, mJ/s

Glass transition

Tg



Melting

Negative peak on thermogram

Ordered to disordered transition

Tm, melting temperature

NB: melting happens to crystalline polymers; glassing happens to amorphous polymers

Temperature, K

Thermogram

dH/d

t, m

J/s Melting

Tm

TYPES OF DSC TECHNOLOGIES:

HEAT FLUX DSC:

It is proposed by Boersma.

The sample and reference cells are heated at a constant rate and thermocouples are used to

detect the temperature differential between sample side and reference side using single, large

mass furnace.

Principle:


Crystallization

Sharp positive peak

Disordered to ordered transition

Material can crystallize!

Observed in glassy solids, e.g., polymers

Tc, crystallization temperature

Temperature, K

Thermogram

dH/d

t, m

J/s

Crystallization

Tc


The introduction of a controlled heat leak between the sample and reference holders enabled

a quantitative measurement of energy changes to be made. Heat flux can be measured

directly if a sample is surrounded by a thermopile.

The peak area is related to the enthalpy change by a calibration factor which is partially

temperature dependent.

Sample holder: sample and reference holders are connected by a low resistance heat flow

path. The material with which the sample holder is made may be aluminium, stainless steel,

platinum.

Sensors: temperature sensors are thermocouples.

Furnace: same block is used for sample and reference.

Temperature controller: temperature difference between sample and reference is measured.

A metallic disc made of constantan alloy is the primary means of heat transfer. Sample and

reference sit on raised constantan discs.

Differential heat flow to sample and reference is measured by thermocouples which are

connected in series, located at the junction of constantan disc and chromel wafers.

With this, it is possible to achieve heating or cooling rates of 1000c /min to 00c /min

(isothermal).

It needs mathematical equations to get the heat flow.

DSC HEAT FLOW EQUATION:

dH/dt = Cp dT/dt + f(T,t)

dH/dt = DSC heat flow signal

Cp = sample heat capacity = sample specific heat x sample weight

dT/dt = heating rate

f(T,t) = heat flow that is a function of time at an absolute temperature (kinetic)

POWER COMPENSATED DSC:



It is developed by Perkin Elmer, USA. It directly measures heat flow between sample side

and reference side using two separate, low mass furnaces.

Principle: An exothermic or endothermic change occurs in the sample, when the sample is

heated, power (energy) is applied or removed from the furnace to compensate for the energy

change occurring in the sample is measured.

The system is maintained in “Thermal Null” state all the times.

The amount of power required to maintain the system in equilibrium is directly proportional

to the energy changes.

Sample holder: it is made up of aluminium, platinum or stainless steel.

Sensors: platinum resistant sensors are generally used. Separate sensors are used for are used

for sample and reference cells.

Furnace: separate blocks of furnace are used for sample and reference cells.

Temperature controller: differential thermal power is supplied to heaters to maintain the

temperature of the sample and reference at the programmed value.

COMPARISION OF DTA AND DSC:

The basic difference between DSC and DTA is that DSC is a calorimetric method in which

differences in energy are measured. In contrast, in DTA, differences in temperature are

recorded. The temperature programs for the two methods are similar. DSC is considered to be

a quantitative technique, in contrast to DTA.

The exact distinction between DSC and DTA instrumentation was the subject of

controversy for many years; it is eventually resolved by Mackenzie. In conventional



(classical) DTA, ∆T is the difference between TS(sample temperature) and

TR(reference temperature).

The junction of difference thermocouple are located in the centre of the sample and

reference specimens. In this arrangement, ∆T cannot be directly related to the

enthalpy change, thus the peak area cannot be reliably converted to energy units.

Classical DTA can provide useful qualitative information, but it can never be more

than semi quantitative.

Quite different from DTA is the power compensation DSC which makes a direct

measurement of the enthalpy change.

S noS no ASPECTASPECT DSCDSC DTADTA

1 Size of the

sample

2-10 mg 50-20mg

2 Sensitivity of the

measurement

a few J/mole 0.5 KJ/mole

3 Heating and

cooling cycles

Programmed heating and

cooling possible

Generally

programmed

heating

4 2

nd order phase

transition

It can be observed with a

sample of 200mg

It is not observed

5 Specific heat

measurement

accurate Not accurate

INSTRUMENTATION:

This instrument works on the temperature control of two similar specimen holders



It consists of two circuits

1. Left half - differential temperature control circuit

2. Right half - average temperature control circuit

In the average temperature control circuit an electrical signal which is proportional to the

dialled temperature of the sample and reference holders, is generated through the

programmer.

In the differential temperature control circuit, signals representing the temperature of sample

and reference are compared. If no reaction taking place in the sample, the differential power

input to the sample and reference heater is almost zero. If a reaction is taking place (∆H is not

zero) a differential power is fed to heaters. A signal proportional to this differential power

along with the sign is transmitted to the recorder pen. The integral of the peak so obtained

gives the internal energy change of the sample.

CLEANING THE SAMPLE CELL:

If the cell gets dirty – Clean it with brush

Brush gently both sensors and cell if necessary

Be careful with TzeroTM thermocouple

Blow out any particles remaining, if any



SAMPLE PREPARATION:

It is possible to use materials which creep, froth or boil if sealed sample sample containers

are used to ensure no damage occurs to the sample holder assembly.

Accurately weighed samples (approx 3 to 20 mg) are encapsulated in the metal pans of high

thermal conductivity.

Small pans of inert treated materials (aluminium, platinum, stainless steel) are used.

Pan configurations may be open, pinhole or hermetically sealed. Same pan material and

configuration for both sample and reference.

Material should entirely cover the bottom of the pan to ensure thermal contact. Avoid

overfilling of the pan to minimize the thermal lag from the bulk of the material to the sensor.

Small sample masses and low heating rates improve resolution but at the expense of

sensitivity.

DONOT DECOMPOSE THE SAMPLES IN DSC CELL

SAMPLE SHAPE:

Cut the sample to uniform shape, do not crush the sample.

If the sample to be taken is pellet, cross section is to be taken.

If the sample material is powder then, it is spread uniformly over the bottom of the sample

pan.

USING SAMPLE PRESS:

When using crimped pans, the pans should not be over crimped.

The bottom of the pans should remain flat, even after crimping.

When using hermetic pans, a little more pressure is required to crimp the pans.

Hermetic pans are sealed by forming a cold wield on the aluminium pans.

SAMPLE SIZE:

Smaller samples will increase the resolution but will decrease the sensitivity.

Larger samples will decrease the resolution but will increase the sensitivity.

Sample size depends on the type of material being measured

If the sample is –

Extremely reactive in nature – very small samples (<1 mg) are to be taken.

Pure organics or pharmaceuticals – 1 to 5 mg

Polymers – approximately 10 mg



Composite materials – 15 to 20 mg

REFERENCE MATERIALS:

An inert material like α-alumina is generally used.

Empty pan can also be used, if the sample weight is small.

With higher sample weights it is necessary to use a reference material, because the total

weight of the sample and its container should be approximately the same as the total weight

of the reference and its container. The reference material should be selected so that it

possesses similar thermal characteristics to the sample.

The most widely used reference material is α-alumina, which must be of analytical reagent

quality. Before use, α-alumina should be recalcined and stored over magnesium perchlorate

in a dessicator.

Kieselguhr is another reference material normally used when the sample has a fibrous nature.

If there is an appreciable difference between the thermal characteristics of the sample and

reference materials, or if values of ∆T are large, then dilution of the sample with the reference

substance is sensible practice. Dilution may be accomplished by thoroughly mixing suitable

proportions of sample and reference material.

PURGE GASES:

Sample may react with air and may oxidize or burn. The problem is overcomed by using inert

gases.

Inert gases are used to control moisture in the surrounding atmosphere. Commonly used inert

gases are nitrogen, helium, argon etc.

Inert gases should ensure even heating and helps to sweep away the off gases that might be

released during sublimation or decomposition.

Nitrogen:

It is the most commonly used inert gas.

It increases the sensitivity of the experiment.

Typical flow rate is 50 ml/min.

Helium:

It has high thermal conductivity.

It increases the resolution of the peaks.

The upper temperature limit for this gas is upto 3500c.

Flow rate is 25 ml/min



Air or oxygen:

Sometimes it is deliberately used to view oxidative effects of the sample.

Flow rate is 50 ml/min

HEATING RATE:

Faster heating rate will increase the sensitivity but will decrease the resolution.

Slow heating rate will decrease the sensitivity but will increase the resolution.

Good starting point is 100c/min.

FACTORS AFFECTING THERMOGRAM:

1) Sample shape:

The shape of the sample has little effect on the quantitative aspect of DSC but more effect on

the qualitative aspects. However, samples in the form of a disc film or powder spread on the

pan are preferred. In the case of polymeric sheets, a disc cut with a cork-borer gives good

results.

2) Sample size:

About 0.5 to 10mg is usually sufficient. Smaller samples enable faster scanning, give better

shaped peaks with good resolution and provide better contact with the gaseous environment.

With larger samples, smaller heats of transitions may be measured with greater precision.

3) Heating rates

4) Atmosphere and geometry of sample holders

There are a number of variables that affect DSC results includes the type of pan, heating rate,

the nature and mass of the compound, the particle size distribution, packaging and porosity,

pre-treatment and dilution of the sample. It is used for purity analysis of above 98% pure

compounds.

DSC: Main Sources of Errors

• Calibration

• Contamination

• Sample preparation – how sample is loaded into a pan

• Residual solvents and moisture.

• Thermal lag

• Heating/Cooling rates

• Sample mass



• Processing errors

MODULATED DSC:

It is introduced in 1993and also developed by TA instruments. It uses heat flux DSC design

but a different furnace heating profile.

Note that temperature is not decreasing during Modulation i.e. no cooling

Modulate +/- 0.42 °C every 40 secondsRamp 4.00 °C/min to 290.00 °C

52

54

56

58

60

62

Mo

du

late

d T

em

pe

ratu

re (

°C)

52

54

56

58

60

62

Te

mp

era

ture

(°C

)

13.0 13.5 14.0 14.5 15.0

Time (min)

In MDSC, a sinusoidal function is superimposed on the overall temperature program to

produce a micro heating and cooling cycle as the overall temperature is steadily increased or

decreased. Using Fourier transformation methods, the overall signal is mathematically

deconvoluted into two parts, a reversing heat flow and a nonreversing heat flow signal. The

reversing heat flow signal is associated with the heat capacity component of the thermogram

and the nonreversing heat flow is related to kinetic processes. Usually step transitions such as

the glass transition, appear only in the reversing heat flow signal and exothermic or

endothermic events may appear either or in both the signals.

A sinusoidal oscillation (a square wave or saw tooth) or oscillation is overlaid on the

traditional linear heating ramp to yield a heating profile in which the sample temperature still

increases with time but not in a linear fashion. The overall effect of this heating profile on the

sample is the same as if two simultaneous experiments were performed. This produces a slow

underlying heating rate (improving resolution) as well as a faster instantaneous heating rate

(improving resolution).

Total heat flow signal contains all the thermal transitions as that of standard DSC.

It also has ability to separate thermal multiple events.



Benefits

• Increased Sensitivity for Detecting Weak (Glass) Transitions

– Eliminates baseline curvature and drift

• Increased Resolution Without Loss of Sensitivity

– Two heating rates (average and instantaneous)

• Ability to Separate Complex Thermal Events and Transitions Into Their Heat

Capacity and Kinetic Components

• Ability to Measure Heat Capacity (Structure) Changes During Reactions and Under

Isothermal Conditions

Disadvantage

• Slow data collection

APPLICATIONS:

1) Determination of crystallinity in a polymer:

DSC evaluation can be used to measure amount of crystallinity in the sample. Let the heat of

crystallization be Hc and total heat given off during melting be Ht.

H=Ht-Hc……(1) where H is the heat given off by that part of polymer, which was already in crystalline state.

Now by dividing H by Hc (specific heat of melting)

Where Hc is the amount of heat given off when 1gm of polymer is melted.

H/Hc=joules/joules/gram=Mc grams

This is total amount of polymer that was crystalline below Tc, crystallization temperature.

So % crystallinity in polymer sample=Mc/Mt *100

Where Mt is total mass of sample taken.

2) DSC purity analysis:

DSC provides a rapid yet reliable method for determining the purity of materials, particularly

pharmaceuticals. The presence of minor impurities may reduce the effectiveness of the drug

or even cause adverse side effects on the patient.

The purity is readily calculated from DSC curve of a single melting event of a few milligrams

of the substance, without the need for reference standard of drug substances.



The determination of purity by means of DSC is based on the assumption that impurities

depress the melting point of pure material according to the eutectic phase diagram behavior.

It is well known that the higher the concentration of impurity present in the sample, the lower

its melting point and broader its melting range. The obtained by DSC includes the complete

melting curve and the latent heat of fusion (∆Hf) of the sample. The interpretation of the DSC

curve is based on a modified form of Vant Hoff equation:

Ts=To-RTo2X1/∆Hf x (1/F)

Where, ∆Hf = heat of fusion of pure major component (J mol-1)

R = gas constant (8.314 J mol-1K-1)

Ts = sample temperature (K)

T0 = theoretical melting point of the pure compound

X1 = mole fraction of impurity

F = fraction of sample melted at Ts

Figure shows phase diagram of two component mixture with eutectic point:

3) Analysis of spray dried system using DSC:

Spray drying is widely used as a means of converting liquids into powder via atomization

into a hot air stream. The liquid droplets are dried prior to contact with the walls of the



chamber, hence the solidification process is very rapid & results in the first instance in

spherical or near sphere particles.

Consequently spray drying may result profound changes to the physical properties of the

material compared to the unprocessed solid form, both in terms of morphology & lattice

structure. In particular spray dried products may be partially or completely amorphous or

alternatively may result in the generation of a range of polymorphic forms.

Ex: spray drying of phenobarbitone from ethanolic solution.

Digitoxin (90); diacetylmide camycin (91) & thiazide diuretics (92). In particular, spray dried products may be partially or completely amorphous or,

alternatively, may result in the generation of a range of polymorphic forms.

Example of the latter include a study on the spray drying of phenobarbitone from ethanolic

solution, reporting the generation of a material that showed characteristics of the Form 111

polymorph after processing in contrast to the commercially available Form 11.

However, the majority of DSC studies on spray-dried systems have focused on the generation

of amorphous material from the process. DSC can be used to study the number and

temperature range of polymorphs, since each polymorphic transition causes an energy change

that may be detected by DSC.

4) Liquid crystals:

DSC is used in the study of liquid crystals. As some forms of matter go from solid to liquid

they go through a third state, which displays properties of both phases.

This anisotropic liquid is known as a liquid crystalline or mesomorphous state. Using DSC, it

is possible to observe the small energy changes that occur as matter transitions from a solid to

a liquid crystal and from a liquid crystal to an isotropic liquid.

5) Screening technique to determine the compatibility of ketoprofen with

excipients:

Differential scanning calorimetry (DSC) was used as a screening technique for assessing the

compatibility of ketoprofen with some excipients currently employed in tablet or capsule

formulations.

The effect of sample treatment (simple blending, cogrinding, compression, kneading) was

also evaluated.



On the basis of DSC results, ketoprofen was found to be compatible with

hydroxyethylcellulose, hydroxypropylcellulose, microcrystalline cellulose, corn starch, arabic

gum, colloidal silica, veegum, lactose, glucose, sorbitol and mannitol.

Some drug-excipient interaction was observed with palmitic acid, stearic acid and stearyl

alcohol and eutectic formation was found with magnesium stearate.

6) In preparation of synthetic polymer blends:

DSC analysis on a blend of synthetic fibres was an early application and it shows that the

DSC is a versatile technique. Using Perkin-Elmer differential scanning calorimeter, a blend

containing Nylon66, Orlon and Vycron polyester was determined. The ∆H values per gram of

the sample were compared with the corresponding ∆H per gram of each pure component.

Hence the ∆H values for the crystallization peaks of nylon and the polyester were measured

together with a cross-linking exotherm of Orlon.

A quantitative analysis was then made on the fibre blend. For example, the ratio of the ∆H

value for the nylon crystallization peak in the fibre blend over the ∆H value for the pure

nylon multiplied by 100 gives the percentage of nylon in the fibre blend. The total time for

analysis, performed without sample treatment or any separatory procedure, was less than

30min. the repeatability of the experiment was found to be within 5% of the amount of each

component present.

Polymer blends difficult to evaluate by conventional DSC have been successfully analysed by

modulated DSC. For example, a polymer blend containing polyethylene terepthalate (PET)

and acrylonitrile-butadiene-styrene (ABS) has been separated and evaluated using MDSC.

CONCLUSION

Differential scanning calorimetry is extremely versatile and able to address a wide

variety of analytical problems.

It is often used in conjunction with TG to obtain better results.

Widespread study of thermal properties on an extensive range of sample types can be

done.

REFERENCES



1. Gurudeep R.Chatwal, Sham K.Anand, Instrumental Methods of Chemical Analysis,

Thermal Methods, 5th edition. (pg no:2.747-2.753)

2. J.Mendham,R.C Denny, J.D Barnes,M.J.K Thomas,Vogels text book quantitative

chemical analysis, pearson education, sixth edition.(pg no.503-521)

3. B.K.Sharma, Instrumental Methods of Chemical Analysis, Thermoanalytical methods,

26th edition, goel publishing house, Meerut,2007. (pg.no.308)

4. Alfred Martin, Physical Pharmacy, Lippincott Williams and Wilkins, USA,B.I

publications, fourth edition, Indian edition.( pg no: 47-48)

5. www.wikipedia.org/wiki/Differential_scanning_calorimetry

6. www.wikipedia.org/wiki/Thermomechanical_analysis

7. www.anasys.co.uk/library/tma1.htm

8. www.ta instruments.com

9. www.setaram.com

CONTENTS


http://www.ta/

http://www.anasys.co.uk/library/tma1.htm


S NO TOPIC PAGE NO

1 Introduction 1

2 Principle 4

3 Output of DSC 7

4 Types of DSC 8

5 Comparison of DSC and DTA 10

6 Instrumentation 11

7 Factors affecting Thermogram 14

8 MDSC 15

9 Applications 16

10 Conclusion 19

11 References 20


thermal analysis

Documents

sample material

energy heat

transition temperature

temperature atwhich

constant temperature

sample inorder

unknown sample

producedby temperature