EVALUASI KESTABILAN

EVALUASI KESTABILAN
SUSPENSI
SUSPENSI
Metode
Metode
Evaluasi
Evaluasi
Suspensi
Suspensi
1. Volume
1. Volume
Sedimentasi
Sedimentasi
( F )
( F )
F = H
F = H
U U
/H
/H
0 0
x 100 %
x 100 %
Harga
Harga
F = > 1 <
F = > 1 <
= yang
= yang
besar
besar
menunjukkan
menunjukkan
produk
produk
yang
yang
baik
baik
Sedimentation volume
Sedimentation volume
-
-
F =
F =
V
V
sed sed
/V
/V
tot tot

The value of F normally lies between 0
The value of F normally lies between 0
to 1 for any pharmaceutical
to 1 for any pharmaceutical
suspension.
suspension.

The value of F provides a
The value of F provides a
qualitive
qualitive
knowledge about the physical stability
knowledge about the physical stability
of the suspension.
of the suspension.
Volume
Volume
Sedimentasi
Sedimentasi
F=0.5 F=1.0 F=1.5
F={ volume sedimen V
u
}/{ volume awal V
o
}
V
o
V
u
V
o
V
u
Degree of flocculation
Degree of flocculation
-
-

=
=
F
F
floc floc
/F
/F
defloc defloc
(
(
V
V
sed sed
/V
/V
tot tot
)
)
floc floc
=
=
-------------------
-------------------
(
(
V
V
sed sed
/V
/V
tot tot
)
)
defloc defloc

When the total volume of both the
When the total volume of both the
flocculated and the deflocculated
flocculated and the deflocculated
suspensions are same, as for example,
suspensions are same, as for example,
100 ml in the Figure; the degree of
100 ml in the Figure; the degree of
flocculation,
flocculation,

= (
= (
V
V
sed sed
)
)
floc floc
/(V
/(V
sed sed
)
)
defloc defloc
2. Kontrol Ukuran Partikel
2. Kontrol Ukuran Partikel

u/ evaluasi adanya agregasi atau

u/ evaluasi adanya agregasi atau
pertumbuhan kristal
pertumbuhan kristal

terjadi perubahan ukuran partikel a/

terjadi perubahan ukuran partikel a/
tidak selama penyimpanan
tidak selama penyimpanan
3
3
.
.
Redispersibilitas
Redispersibilitas
4.
4.
Penentuan
Penentuan
Rheologi
Rheologi

selama
selama
penyimpanan
penyimpanan
ada
ada
perubahan
perubahan
atau
atau
tidak
tidak

viskositas
viskositas
dan
dan
tipe
tipe
alir
alir
5.
5.
Mudah
Mudah
tidaknya
tidaknya
suspensi
suspensi
dituang
dituang
1) Temperature fluctuations:
- Small particle dissolve more easily
2) Ostwald ripening (or coarsening):
- Solubility in the near vicinity of small
particles is higher than in the near vicinity
of large particles (isothermal process)
- Particles also become more spherical
Particle size increases with time due to:
Instability particle size distribution
Temperature fluctuations
Usually solubility increases with increasing temperature
Temperature increase Temperature decrease
Ostwald ripening (1)

L
(a)
1

L
(a)
2

S
(a)
1

S
(a)
2
Smaller radius of the curvature of particle 1 is than of particle 2
Particle 1
Particle 2
chemical potential, , increases with increasing pressure
Pressure difference over curved surface (La Places law):
r
2
p

pressure in particle 1 > pressure in particle 2

S
(a)
1
>
S
(a)
2
Ostwald ripening (2)

L
(a)
1

L
(a)
2
x(a)
1
x(a)
2

S
(a)
1

S
(a)
2

S
(a)
1
>
S
(a)
2

L
(a)
1
>
L
(a)
2

(a) + RT ln x(a)
1
>
L

(a) + RT ln x(a)
2
At equilibrium:
S
(a)
1
=
L
(a)
1
en
S
(a)
2
=
L
(a)
2
x(a)
1
> x(a)
2
Packaging and Storage of Suspensions:
Packaging and Storage of Suspensions:

1) Should be packaged in wide mouth
1) Should be packaged in wide mouth
containers having adequate air space above
containers having adequate air space above
the liquid.
the liquid.

2) Should be stored in tight containers
2) Should be stored in tight containers
protected from: freezing and excessive
protected from: freezing and excessive
heat & light
heat & light

3) Label:
3) Label:
"Shake Before Use"
"Shake Before Use"
to ensure
to ensure
uniform distribution of solid particles and
uniform distribution of solid particles and
thereby uniform and proper dosage.
thereby uniform and proper dosage.
ASA
SA
SA