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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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