Bambang H Nugroho, M.Sc.

, Apt
Pengertian SistemDispersi
Sifat Antarmuka Suspensi
Formulasi Suspensi Formulasi Suspensi
Karakteristik Suspensi
Stabilitas Fisik Suspensi
DISPERSE SYSTEMS
Definition:
- A substance, the disperse (discontinuous) phase, is
dispersed as particles over the dispersion medium
(continuous phase)
- Phases can be solids, liquids or gasses - Phases can be solids, liquids or gasses
Disperse phase
(discontinuous phase)
Dispersie medium
(continuous phase)
What is a dispersion at molecular level?
What makes them physically stable?
Interfacial Phenomena
Coarse dispersion 10 to 50 m Coarse dispersion 10 to 50 m
Fine dispersion 0.5 to 10 m
Colloidal 1 nm to 0.5 m
What happens at interface is critical!!
Suitable For Drugs with low solubility
Pharmaceutical suspensions are uniform dispersions of
solid drug particles in a vehicle in which the drug has
minimum solubility.
Colloidal suspension 1 nm to 0.5 m
Coarse suspension 1 to 100 m
May be for oral, ophthalmic, parenteral, or topical use
Oral suspensions may be aqueous preparations with
flavored, sweetened vehicles or powder products for
oral suspension
Marketed preparations:
ready-to-use
dry powders which must be reconstituted before administration
Surface Free
Energy (Gibbs)
Surface Tension
(Solid-Liquid)
Surface Area
Compute if surface is increased
1010
7
G
1
=
SL
x A
= 100 X 10= 10
5
erg/cm
G
2
=
SL
x A
= 100 X 10
7
=10
9
erg/cm
G
21
10
5
erg/cm 10
9
erg/cm
Energy (Gibbs) (Solid-Liquid)
Compute if surface is
increased 1010
7
cm

SL
=100 dyne/cm
THERMODINAMICALY
UNSTABLE
BULK
THERMODINAMICALY
UNSTABLE
caking
Dispersion
flocculation or caking
determined by forces of attraction (van der Waals)
versus forces of repulsion (electrostatic)
deflocculated
repulsion> attraction
affected by [electrolytes]
flocculated
attraction > repulsion
Electric Double Layer
-
-
-
-
-
+
+
+
+
+
+
-
+
+
-
+
+
-
+
-
+
+ -
+
tightly
bound
diffuse
electroneutral
bulk
-
-
+
+
+
+
+
-
-
+ +
-
-
+
+
gegenion
Nernst potential
zeta potential
bulk
Electrical Double Layer Electrical Double Layer
-
-
-
-
-
-
-
-
+
+
+
+
Electroneutral solution
Surface charge
Stern layer (fixed)
Zeta potential
Nernst potential
Electrical Props contd
Nernst potential
potential difference between the actual
solid surface and the electroneutral bulk
Zeta potential Zeta potential
potential difference between the tightly
bound layer and the bulk
governs electrostatic force of repulsion
between solid particles
The DLVO theory is named after
Derjaguin, Landau, Verwey, and
Overbeek. It is the explanation
of the stability of suspension.
Describes the balance between
two forces, electrostatic
repulsion and van der Waals
attraction.
Electrostatic repulsion becomes
12/19/2013 Farmasi Fisik 2013-Bambang HN 12
Electrostatic repulsion becomes
significant when two colloids
approach each other and their
electrical double layers begin to
interfere.
Resuspend easily upon shaking
Settle slowly after shaking
Homogeneous mix of drugPhysically and Homogeneous mix of drugPhysically and
chemically stable during its shelf life
Sterile (parenteral, ocular)
Gets into syringe (parenteral, ocular)
Deflocculated suspension Flocculated suspension
KARAKTERISTIK SUSPENSI
NEED ANTI CAKING AGENT
NEED FLOCULATING AGENT
Controlled Flocculation
electrolytes
most widely used
reduce zeta potential
decrease force of repulsion
change pH
bridge formation
alcohol
polymers
adsorb to particle surface
bridging
viscosity, thixotropy
protective colloid action
most effective
alcohol
reduction in zeta potential
surfactants
form adsorbed monolayers on
particle surface
efficacy is dependent on charge,
concentration
State Rate of settling Sedimentation
volume
Nature
Flocculated Fast High Porous, easy to
redisperse
Deflocculated Slow Low Compact, difficult
to redisperse
Particles should settle slowly
Formulation should allow the easy
redispersion of sedimented particles
A flocculated suspension is desirable than A flocculated suspension is desirable than
a deflloculated suspension
A suspension should not be too viscous to
reduce the sedimentation rate
The suspension shall form
loose networks of flocks
that settle rapidly, do not
form cakes and are easy to
resuspend.
flock
resuspend.
Settling and aggregation
may result in formation of
cakes (suspension) that is
difficult to resuspend or
phase separation (emulsion)
cake
Cake & Flock must be Controlled
by Zeta Potensial, Viscosity and
Particle Size
12/19/2013 Farmasi Fisik 2013-Bambang HN 20
PENGARUH ZETA POTENSIAL TERHADAP SISTEM DISPERSI
Stokes law:
18 18 18 18
d
2 22 2
( ( ( (
s
-
f
)g
v =
Take care:
- Wetting particles (contact angle)
- Shape of the particles (compare: parachute)
- High particle concentration
- Non-Newtonian liquids (yield stress)
- Convection by differences in temperature
F = Vu /V0 ; ideally, F should be equal to 1.0
BACK
Stokes law:
18 18 18 18
d
2 22 2
( ( ( (
s
-
f
)g
v =
- Decreasing particle size, d
- Decreasing difference in density,
s
-
f

- Increasing viscosity,
Pseudoplastis
(semakin di beri gaya
semakin encer-
Tidak diberi gaya
Kental) Kental)
INGAT!
Rate of share
Berbanding
terbalik dengan
Visikositas
Combination for
good suspending
medium
(Thixtotrpy- (Thixtotrpy-
Pseudoplatis)
Determine the absolute viscosity of syrup using a ball of radius of 0.2 cm.
The density of the ball is 2.33g/cc and the density of the syrup is 1.33 g/cc
at 250 C. The rate of falling is 4.35 cm/sec.
Determine the velocity of settling of sulfur in water. The average particle
radius is 5.5 m. The density of sulfur and water at 250 C. is 1.96 and
0.997 g/cc., respectively. The viscosity of water at 250 C. is 0.00895 poise. 0.997 g/cc., respectively. The viscosity of water at 250 C. is 0.00895 poise.
If the height of the bottle is 10 cm how long will it take to completely
settle?
Particle size determination:
From the previous example, calculate the average particle size of sulfur.
What is the necessary viscosity to reduce the sedimentation rate from
0.0071 cm/sec to 0.00071 cm/sec?