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STABILITY ANALYSIS

IN SOLID STATEDOSAGE FORMS

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Morphology

SEM picture

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Melting point

Binary system

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Ternary system

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Solubility/dissolution rate

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Mass changes

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Water sorption

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Examples of water sorption-desorption isotherms of two polymorphs.

The two polymorphs, A and B, transform into the same hydrated form.

The metastable form B takes up water a lower RH than the stable form

A. The hydrate form loses water at RH values below 20%

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Impurity content

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Differential Scanning

Calorimetry

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Definitions

A calorimetermeasures the heat into or out of a

sample.

A differential calorimeter measures the heat of a

sample relative to a reference. A dif ferential scanning calorimeterdoes all of the

above and heats the sample with a linear temperature

ramp.

Endothermicheat flows into the sample.Exothermicheat flows out of the sample.

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Differential Scanning Calorimetry (DSC) measures the

temperatures and heat flows associated with transitions in

materials as a function of time and temperature in a

controlled atmosphere.

These measurements provide quantitative and qualitative

information about physical and chemical changes that

involve endothermicor exothermic processes, or changes

in heat capacity.

DSC: The Technique

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Conventional DSC

Metal

1

Metal

2

Metal

1

Metal

2

Sample Empty

Sample

TemperatureReference

Temperature

Temperature

Difference =

Heat Flow

A linear heating profile even for isothermal methods

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What can DSC measure?

Glass transitions

Melting and boiling points

Crystallisation time and temperature

Percent crystallinityHeats of fusion and reactions

Specific heat capacity

Oxidative/thermal stability

Rate and degree of cure

Reaction kinetics

Purity

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6

DSC Thermogram

Temperature

H

eatFlow

->exothermic

Glass

Transition

Crystallisation

Melting

Cross-Linking

(Cure)

Oxidation

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79.70C(I)

75.41C81.80C

144.72C

137.58C20.30J /g

245.24C

228.80C22.48J /g

Cycle 1

-0.5

0.0

0.5

1.0

1.5

HeatFlow

(W/g

)

0 50 100 150 200 250 300

Temperature (C)

Sample : PET 80PC 20_MM1 1minSize : 23.4300 mgMethod: standard dsc heat -cool-heatComment: 5/4/06

DSCFile: C :...\DSC \Melt Mixed 1\PET 80PC 20_MM1.001Operator: SACRun Date : 05-Apr-2006 15 :34Instrument: DSC Q 1000 V9.4 Build 287

Exo Down Universal V 4.2E TA Instruments

Technical Group TalkTechnical Group Talk

Example DSC - PET

Tg

Tc

Tm

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670

Influence of Sample Mass

Temperature (C)

150 152 154 156

0

-2

-4

-6

DSCHeatFlow(W/g)

10mg

4.0mg

15mg

1.7mg

1.0mg

0.6mg

Indium at10C/minuteNormalized Data

158 160 162 164 166

Onset notinfluenced

by mass

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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

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Transformation of a soluble bi-methanesulfonate in the less soluble monosalt

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Applications of X ray Powder Diffractiondiffraction = elastic scatteringmomentum transfer at constant energy, i.e. incident l = diffracted l

Used for: identification of materials/phases determination of structural details, i.e. local

environments within an extended structure evaluation of order and disorder in structures phase transitions (structural distortions

or reconstruction) chemical reactions relate structure and properties

40 60 80 1000

100

200

300

400

500

600Si powder neutron diffraction patternC2 Chalk Riverl= 1.329

Intensity

(counts)

2(0)

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Routine Powder X-ray Diffraction:

Powder X-ray diffractogrammatched with the PDF database

links to crystallographicdata if available (i.e structuredetails from ICSD)

semi-quantitative analysis

D

S

A

M

Position [2Theta]

20 30 40 50 60

Counts

0

2500

10000

group-1_1

Visible Ref. Code Chemical

Formula

red 01-073-2141 La2 O3

blue 00-005-0378 Ba C O3

green 01-089-5898 Cu O

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Comparison of X-ray diffractograms of the acetate salt and the precipitate obtained

in acetate buffer

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Comparison of X-ray diffractograms of crystals and amorphs

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IR SPECTROFOTOMETRY

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