STABILITY ANALYSIS

IN SOLID STATE
DOSAGE FORMS
Morphology
SEM picture
Melting point
Binary system
Ternary system
Solubility/dissolution rate
Mass changes
Water sorption
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%
Impurity content
Differential Scanning
Calorimetry
Technical Group Talk
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 differential scanning calorimeter does all of the
above and heats the sample with a linear temperature
ramp.
Endothermicheat flows into the sample.
Exothermicheat flows out of the sample.
Technical Group Talk
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 endothermic or exothermic processes, or changes
in heat capacity.
DSC: The Technique
Technical Group Talk
Conventional DSC
Metal
1
Metal
2
Metal
1
Metal
2
Sample Empty
Sample
Temperature
Reference
Temperature
Temperature
Difference =
Heat Flow
A linear heating profile even for isothermal methods
Technical Group Talk
What can DSC measure?
Glass transitions
Melting and boiling points
Crystallisation time and temperature
Percent crystallinity
Heats of fusion and reactions
Specific heat capacity
Oxidative/thermal stability
Rate and degree of cure
Reaction kinetics
Purity
Technical Group Talk
6
DSC Thermogram
Temperature
H
e
a
t

F
l
o
w

-
>

e
x
o
t
h
e
r
m
i
c
Glass
Transition
Crystallisation
Melting
Cross-Linking
(Cure)
Oxidation
79.70C (I)
75.41C
81.80C
144.72C
137.58C
20.30J /g
245.24C
228.80C
22.48J /g
Cycle 1
-0.5
0.0
0.5
1.0
1.5
H
e
a
t

F
l
o
w

(
W
/
g
)
0 50 100 150 200 250 300
Temperature (C)
Sample : PET 80PC 20_MM1 1min
Size : 23.4300 mg
Method: standard dsc heat -cool-heat
Comment: 5/4/06
DSC
File: C:...\DSC \Melt Mixed 1\PET 80PC 20_MM1.001
Operator: SAC
Run Date : 05-Apr-2006 15 :34
Instrument: DSC Q 1000 V9.4 Build 287
Exo Down Universal V 4.2E TA Instruments
Technical Group Talk Technical Group Talk
Example DSC - PET
T
g
T
c
T
m
Technical Group Talk
6 70
Influence of Sample Mass
Temperature (C)
150 152 154 156
0
-2
-4
-6
D
S
C

H
e
a
t

F
l
o
w

(
W
/
g
)
10mg
4.0mg
15mg
1.7mg
1.0mg
0.6mg
Indium at
10C/minute
Normalized Data
158 160 162 164 166
Onset not
influenced
by mass
Technical Group Talk
6
Effect of Heating Rate
on Indium Melting Temperature
154 156 158 160 162 164 166 168 170
-5
-4
-3
-2
-1
0
1
Temperature (C)
H
e
a
t

F
l
o
w

(
W
/
g
)
heating rates = 2, 5, 10, 20C/min
Technical Group Talk
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
Transformation of a soluble bi-methanesulfonate in the less soluble monosalt
Applications of X ray Powder Diffraction
diffraction = elastic scattering
momentum 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 80 100
0
100
200
300
400
500
600
Si powder neutron diffraction pattern
C2 Chalk River
l = 1.329
I
n
t
e
n
s
i
t
y

(
c
o
u
n
t
s
)
2 (
0
)
Routine Powder X-ray Diffraction:
Powder X-ray diffractogram
matched with the PDF database
links to crystallographic
data if available (i.e structure
details 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
Comparison of X-ray diffractograms of the acetate salt and the precipitate obtained
in acetate buffer
Comparison of X-ray diffractograms of crystals and amorphs
IR SPECTROFOTOMETRY