Transcript Pharmaceutical Suspensions

PHARMACEUTICAL
SUSPENSIONS AND
EMULSIONS
Coarse Dispersions
(Lyophobic colloids)
• Suspension: Solid drug in liquid vehicle
• Emulsion: Liquid drug in liquid vehicle:
 Oil-in-water
emulsions (o/w)
 Water-in-oil (w/o)
Reasons for Use
 Drug
is insoluble
 Drug is more stable in
suspension or emulsion
 There is a need to control the
rate of release of the drug
 Drug has bad taste (oral)
Routes of Administration
 Oral
 Ocular
 Otic
 Rectal
 Parenteral
 Topical
I. Formulation of
Suspensions
Wetting
Wetting agent
Well Formulated
Suspension
 Resuspend
easily upon shaking
 Settle rapidly after shaking
 Homogeneous mix of drug
 Physically and chemically stable
during its shelf life
 Sterile (parenteral, ocular)
 Gets into syringe (parenteral, ocular)
“External” Forces Acting
on Particles
Gravity
Brownian Movement
V(-o)g
 Sedimentation
equilibrium: Gravity is
neutralized by
Brownian movement
2-5 m
Settling and Aggregation

The suspension shall
form loose networks of
flocks that settle rapidly,
do not form cakes and
are easy to resuspend.

Settling and aggregation
may result in formation of
cakes (suspension) that
is difficult to resuspend or
phase separation
(emulsion)
flock
cake
Sediment Volume
F={volume of sediment Vu}/{original volume Vo}
•Vu
•Vo
•Vo
•Vu
F=0.5
F=1.0
F=1.5
DLVO: Optimal Distance
Energy
No flocks can form
Repulsion
Attraction
Attraction
Distance
Controlled Flocculation
 Flocculating
+
-
agent
changes zetapotential of the
particles (it can be
Non-caking
electrolyte,
Caking
Caking
charged surfactant
or charged polymer
F=Vu/Vo adsorbing on a
surface).
 If the absolute
value of the zetapotential is too high
Flocculating Agent
the system
deflocculates
+
because of
increased repulsion
Zeta-potential
and the dispersion
cakes.
II. Formulation of
Emulsions
Emulsification
Emulsifier
HLB and Use of Surfactants
Amphiphilic surfactants are characterized by
the hydrophilic-lipophilic balance (HLB): a
relative ratio of polar and non-polar groups in
the surfactant
HLB ca. 1 to 3.5: Antifoams
HLB ca. 3.5 to 8: Water-in-Oil Emulsifiers
HLB ca. 7 to 9: Wetting and spreading agents
HLB ca. 8 to 16: Oil-in-Water Emulsifiers
HLB ca. 13 to 16: Detergents
HLB ca. 15 to 40: Solubilizers
Required HLB
HLB needed for emulsification of the oil phase. If
there are several oil ingredients the required HLB
is calculated as a sum of their respective required
HLB multiplied by the fraction of each.
Calculate the required HLB for the oil phase of the following
o/w emulsion: cetyl alcohol 15 g., white wax 1g. Lanolin 2 g,
emulsifier (q.s.), glycerin 5 g. water 100 g.
Required HLB
Cetyl alcohol
White wax
Lanolin
Total required HLB
(from reference)
15
x
15/18
12
x
1/18
10
x
2/18
Fraction
12.5
0.7
1.1
14.3
HLB of Surfactant Blend
Surfactant blends are commonly used to obtain
desired emulsifying properties.
What is the HLB of the mixture of 40 % Span 60
(HLB = 4.7) and 60 % Tween 60 (HLB = 14.9)?
HLB of mixture:
4.7 x 0.4 + 14.9 x 0.6 = 10.8
In what proportion should Span 80 (HLB = 4.3) and
Tween 80 (HLB = 15.0) be mixed to obtain
“required” HLB of 12.0?
4.3.(1-x) + 15.x = 12
x = 0.72
72 % Tween 80 and 28 % Span 80