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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

>=='7-91

>@7'<?91-.'@.6g

-=<'-=91

--?'?.91--'=?6g

1ycle>

%.'<

.'.

.'<

>'.

>'<

   +  e  a   t   F   l  o  $   :   !   6  g

   ;

. <. >.. ><. -.. -<. @..

 Teperature:91;

Saple 5ET?.51-.CMM> >inSie -@'=@..gMetho&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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