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VAISHNAVI PATIL1ST M-PHARMMMCP BELGAUM.

THERMO ANALYTICAL METHODS OF ANALYSIS

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DEFINITION

Differential scanning calorimetry measures the temperatures and heat flows associated with transitions in the materials as a function of time and temperature in a controlled atmosphere

It provides quantitative and qualitative information about physical and chemical changes that involve exothermic and endothermic or changes in heat capacity

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DSC can measure….

Glass transitions Melting and boiling points Crystallization time and temperature Heats of fusion and reactions Specific heat capacity Oxidative/thermal stability Reaction kinetics Purity

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TYPES OF DSCHyper-DSC

Based on principle that high heating rates give large broad transitions.

•Heating rates typically 400-500oC/min

•Need very small sample sizes (~nanograms)

Advantages:

•A quick overview of new sample

•Picking out minute transition

Disadvantages:

•Accuracy: transitions can be shifted by as much as 40oC

•Repeatabiliy: Very sensitive to thermal lag.

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Modulated DSC

• Composite heating profile: • Determines heat capacity and separates heat flow into that due to

reversible and non-reversible events.

Typically:

Heating rates: 0 - 50C

Modulation:

Period: 60 second

Amplitude: +/-10C

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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

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Mod

ulat

ed T

empe

ratu

re (

°C)

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Tem

pera

ture

(°C

)

13.0 13.5 14.0 14.5 15.0

Time (min)

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REQUIREMENTS for DSC Sample sizes for DSC range from 0.1 to 10mg.

Heating rates between 10 and 20 C = min are ⁰common in pharmaceutical studies.

The sample should be finely divided to provide good thermal contact with the block and the thermocouple.

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INSTRUMENTATION

It consists of…. Sample holder Furnace/heating device Temperature programmer Recording device Atmosphere control Cooling control

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SAMPLE ASSEMBLY

Two types of sample assembly

1. Design for temperature above 500 0C

2. Design for temperature below 500 0C

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1. Design for temperature above 500 0C

In this the sample or reference thermocouple heads fit underneath the metal pans containing sample or reference material. It is surrounded by metallic or ceramic block.

This block ensures even heat distribution. Flushing of the sample assembly is by using

a selected gas atmosphere and also cooling facility is applied for the rapid return to ambient temperature.

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2. Design for temperature below 500 0C

The disc or plate thermocouples are used as platforms for the sample or reference container pans, which have flat bottom.

This gives a high sensitivity for low mass of sample

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FURNACE

A uniform hot zone. Linear heating rates. Should of low mass. Designed to preclude electrical interaction

effects (Nichrome wire – upto1000 0C, platinum wire - 1500 0C)

Should have cooling facility for rapid return to ambient temperature.

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PROGRAMMER

It should be capable of giving a wide range of heating and cooling rates, ex: temperature should rise from 1 to 50 0C /min

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RECORDER SYSTEM

It contains an amplifier for signals from temperature (T) sensor & differential temperature (∆T) thermocouples.

These signals will be recorded on a twin pen recorder.

It should have range of sensitivity settings, so that peak width as well as height may be varied by the operator.

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INTERPRETATIONS

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There are three methods to measure the peak areaCut and weigh methodPlanimeter methodIntegrated method

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Cut and weigh method

This is usually done on a photocopy of the record, so that the original may be preserved.

The area may be obtained by comparison with a square cut from the same paper.

The method is accurate to within +/- 5%

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Planimeter method

This involves the tracing the perimeter of a peak on the DSC record with a stylus connected to a planimeter arm.

The area will be registered on the planimeter dial.

This method eliminates errors like inaccurate cutting & variations from paper quality.

Gives accurate reading within +/- 1%

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Integrator Method

It consist of an electronic device that automatically measures the area under a peak accurately. Thus, the number of calories or joules corresponding to particular transition.

It is the most accurate method.

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ADVANTAGES instruments can be used at very high temperatures

• instruments are highly sensitive

• characteristic transition or reaction temperatures can be accurately

determined

DISADVANTAGES• uncertainty of heats of fusion, transition, or reaction estimations is 20-

50%

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FACTORS AFFECTING DSC

Sample weight Particle size Heating rate Atmospheric conditions Conditions of sample packing into dishes

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APPLICATIONS

Pharmaceutical analysis are in quantitative identification and purity assessment of raw materials. It can be accomplished by comparing the DSC curves of the sample to that of a reference curve.

Studying the compatibility of drugs and excepients in formulation work.

Impurities may be detected by depression of the melting point ,the appearance of transitions, etc.

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Study thermal stability of inorganic compounds.

DSC offers a wide spectrum of useful investigations related to reaction kinetics, polymerization, solvent retention, phase- transformation, solid-phase reactions and curing or drying properties of a product.

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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

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REFERENCE

Pharmaceutical Drug Analysis –Ashutosh Kar

Pharmaceutical Analysis (VOL II) – by Dr. A V Kasture

Thermal methods by-James W. Dodd & Kenneth H. Tonge

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