stability analysis in solid state dosage forms
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STABILITYANALYSIS IN
SOLID STATEDOSAGE FORMS
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Morphology
• SEM picture
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Melting point
• Binary syste
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Ternary syste
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Solubility/dissolution rate
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Mass changes
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!ater sorption
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E"aples o# $ater sorption%&esorption isothers o# t$opolyorphs' The t$o polyorphs( A an& B( trans#orinto the sae hy&rate& #or' The etasta)le #or Bta*es up $ater a lo$er R+ than the sta)le #or A' The
hy&rate #or loses $ater at R+ ,alues )elo$ -./
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Ipurity content
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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 uantitative and ualitative
information about physical and chemical changes that
involve endothermic or exothermic processes! or changes
in heat capacity.
DSC: The Technique
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What can DSC measure?
•Glass transitions
•Melting and boiling points
•Crystallisation time andtemperature
•5ercent crystallinity
•Heats of fusion and reactions
•Speci4c heat capacity
•O"i&ati,e6theral sta)ility
•Rate and degree of cure
•Reaction *inetics
•5urity
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*
DSC Thermogram
Temperature
(
e a t ) l o w
+ , e - o t h e r m i c
lass
Transition
Crystallisation
"elting
Cross+/in0ing
(Cure)
1-idation
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78'7.91:I;
7<'=>91?>'?.91
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Teperature:91;
Saple 5ET?.51-.CMM> >inSie -@'[email protected]&stan&ar& &sc heat%cool%heat1oent <6=6.
DS1File 1'''DS1Melt Mi"e&>5ET?.51-.CMM>'..>Operator SA1Run Date .<%Apr%-.. ><@=Instruent DS1 >... H8'= Buil&-?7
E"o Do$n ni,ersal H='-E TA Instruents
Technical Group Tal* Technical Group Tal*
Example DSC - PET
Tg
Tc
T
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*23
Influence of Sample ass
Temperature !"C#
$%& $%' $%( $%)
&
-'
-(
-)
DSC*e a
t+lo,
!W-g#
$&mg
(.&mg
$%mg
$./mg
$.&mg
&.)mg
In0ium at$&"Cminute1ormali2e0 Data
$%3 $)& $)' $)( $))
1nset notinfluenced
by mass
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*
Effect of *eating 4ateon In0ium elting 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 ' $! 4! #3! $35C6min
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DSC: ain Sources of Errors
•1ali)ration
•1ontaination
•Saple preparation J ho$ saple is loa&e& into apan
•Resi&ual sol,ents an& oisture'
• Theral lag
• +eating61ooling rates
• Saple ass
•5rocessing errors
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ns#oration o# a solu)le )i%ethanesul#onate in the less solu)le onosalt
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Routine Powder X-ray Diffraction:
• Powder X-ray diffractogram matched with the P! data"ase• lin#s to crystallographicdata if availa"le (i.e structuredetails from $%&)
• semi-'uantitative analysis
(o$ition )*2+heta,
20 30 40 50 60
Count$
0
2500
10000
-roup.1/1
7isible &ef. Code Chemical
ormula
red 3#+328+$#9# /a$ 18
blue 33+334+382: ;a C 18
green 3#+3:<+4:<: Cu 1
D
S
A
M
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parison o# K%ray &i0ractogras o# the acetate salt an& the precipitate o)taineacetate )u0er
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1oparison o# K%ray &i0ractogras o# crystals an& aorphs
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IR S5E1TROFOTOMETRY
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