Pharmaceutical suspensions sb

Introduction to Pharmaceutical Suspension

1. PHARMACEUTICAL
SUSPENSIONS
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)

2. 2
Ø
Definition.
Ø
Classification.
Ø
Benefits & Limitations
Ø
Applications
Theoretic consideration of
suspensions
Ø
Formulation of suspensions
•
Sedimentation
•
Brownian movement
•
Electrokinetic properties
CONTENTS

3. 3
3
WHY WE ARE USING SUSPENSIONS?

4. 4
The
reasons
for the formulation of a
pharmaceutical suspension:
when the drug is insoluble in the delivery vehicle
To mask the bitter taste of the drug
To increase drug stability
To achieve controlled/sustained drug release

5. 5
5
Suspension can improve chemical stability of certain drug.
E.g. Procaine penicillin G.
Ø
Drug in suspension exhibits higher rate of
bioavailability
than other dosage forms.
Solution > Suspension > Capsule > Compressed Tablet
> Coated
tablet
Duration and
onset of action
can be controlled.

E.g. Protamine Zinc-Insulin suspension.
Suspension can mask the unpleasant/ bitter taste of drug.
E.g. Chloramphenicol
BENIFITS

6. 6
6
Physical
stability
, sedimentation and compaction can
causes problems.
Ø
It is bulky sufficient care must be taken during
handling and
Ø
transport.
Ø
It is difficult to formulate.
Ø

Uniform and accurate dose can not be
achieved
unless suspension are
packed in unit
dosage form.

LIMITATIONS

7. 7
7
Ø

The suspended particles should not settle rapidly and
sediment

produced, must
be easily re-suspended
by the use
of moderate

amount of
shaking
.
Ø
It should be easy to pour yet
not watery
and
no grittiness.
Ø
It should have
pleasing odour
,
colour and palatability
.
Ø
Good
syringeability
.
Ø
It should be
physically,chemically and microbiologically
stable
.
Ø
Parenteral /Ophthalmic suspension should be sterilizable.
Features Desired In Pharmaceutical
Suspensions

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WHAT ARE SUSPENSIONS?

9. 9
•
The term "
Disperse System
" refers
to a system in which one substance
(
The Dispersed Phase
) is
distributed, in discrete units,
throughout a second substance (
the

continuous Phase
).

•
Suspensions are heterogenous
system consisting of 2 phases.
9
DISPERSE

SYSTEM

10. 10
10
A solid in liquid dispersion
,
in which the
particle
size is more than
colloidal size.
DISPERSE SYSTEM
DISPERSION MEDIUM
DISPERSED PHASE
o
Aqueous / oily liquid
o
Insoluble solid

11. 11
11
Definition
Ø
A Pharmaceutical suspension is a coarse dispersion in
which internal phase (
therapeutically active
ingredient
)is dispersed uniformly throughout the
external phase.

12. 12
Ø

The
internal phase
consisting of
insoluble solid particles having a range
of size(
0.5 to 5 microns
) which is
maintained uniformly through out the
suspending vehicle with aid of
single
or combination of suspending agent.
Ø
The external phase (
suspending
medium
) is generally aqueous in some
instance, may be an organic or oily
liquid for non oral use.
12

13. 13
Classification

•
Based On rout of administration

Oral suspension
Externally applied suspension
Parenteral suspension
•
Based On Electrokinetic Nature Of
Solid Particles

Flocculated suspension
Deflocculated suspension

14. 14
14
In flocculated suspension,
formed flocs (loose
aggregates
) will cause increase in sedimentation
rate due to increase in size of sedimenting particles.
Ø
Hence, flocculated suspensions sediment more
rapidly.
Ø
Here, the sedimentation depends
not only on the
size
of the flocs but also on the porosity of flocs.
Deflocculation and flocculation
(
Flocculated Suspensions)

15. 15
15
Deflocculated suspensions
Ø
In deflocculated suspension, individual
particles are settling.
Ø
Rate of sedimentation is slow , which
prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.
Ø
This phenomenon called
‘
caking
’
or
‘
claying
’
.
Ø
In deflocculated suspension larger particles
settle fast and smaller remain in supernatant
liquid so supernatant appears cloudy.

16. 16

Theory of Suspensions
•
Sedimentation Behaviour
•
Sedimentation means settling of particle or
floccules under gravitational force in liquid
dosage form.
•
Velocity of sedimentation expressed by
Stokes Equation
16

17. •
Where, v
sed.
= sedimentation velocity in cm / sec
•
d = diameter of particle
•
ρ

s
= density of disperse phase
•
ρ
o
= density of disperse media
•
g = acceleration due to gravity
•
η

= viscosity of disperse medium in poise

Stokes Equation
17

18. 18

Limitation of Stoke
’
s Equation
 
.
Stoke's equation applies only to:
Spherical particles in a
very dilute suspension
(0.5 to 2 gm per 100 ml)
Ø
Particles which
freely settle without collision
.
Ø
Particles with
no physical or chemical
attraction.

19. 19
19
Sedimentation Parameters
Sedimentation volume (F) or height
(H) for flocculated suspensions:
Definition:
Sedimentation volume is a ratio of the
ultimate volume of sediment (Vu) to the
original volume of sediment (Vo)
before settling.
F = V
u
/ V
o
Where,
V
u
= final or ultimate volume of sediment
V
o
= original volume of suspension before settling

20. 20
20
F has values ranging from less than one to greater
than one.

When F < 1 Vu < Vo
When F =1 Vu = Vo
The system is in flocculated equilibrium and show no
clear supernatant on standing.
When F > 1 Vu > Vo
Sediment volume is greater than the original volume
due to the network of flocs formed in the suspension
and so loose and fluffy sediment

21. 21
21
The sedimentation volume gives only a qualitative
account of flocculation
.

Fig : Suspensions quantified by sedimentation
volume (f)

22. 22
22

Degree of flocculation (
β
)
It is the ratio of the sedimentation volume of
the
flocculated suspension
,F , to the
sedimentation volume of the
deflocculated
suspension,
F
∞
ß
= F / F
∞
(Vu/Vo) flocculated
ß
= --------------------
(Vu/Vo) deflocculated
Ø
The minimum value of
ß
is 1,when
flocculated suspension sedimentation
volume is equal to the sedimentation
volume of deflocculated suspension.

23. 23
23
.
Brownian Movement
Brownian movement of particle prevents
sedimentation

by keeping the dispersed material in
random motion.
Ø
Brownian movement depends on the
density of
dispersed

phase
and
the density and viscosity of
the disperse medium
.
Ø
The kinetic bombardment of the particles by the
molecules of the suspending medium will keep the
particles suspending, provided that their size is below
critical radius (r).

24. 24
24
Electro kinetic Properties

The
zeta potential
is defined as the difference in
potential between the surface of the tightly bound layer
(shear plane) and electro-neutral region of the solution.

25. 25
25
Ø
Zeta potential has practical application in
stability
of systems
containing dispersed particles .
Ø
If the zeta potential is reduced below a certain
value, the attractive forces exceed the repulsive
forces, and the particles come together.
Ø
This phenomenon is known as
flocculation
Ø
The flocculated suspension is one in which zeta
potential of particle is -20 to +20 mV
Ø

Thus the phenomenon of flocculation and
deflocculation depends on zeta potential carried
by particles
.

26. 26
26
Ø

The formulation of a suspension depends on
whether the suspension is flocculated or deflocculated.
Ø
Three approaches are commonly involved
1.
Use of structured vehicle
2.
Use of controlled flocculation
3.
Combination of both of the methods
:FORMULATION OF SUSPENSIONS

27. 27
27
Ø
Structured vehicles called also
thickening or
suspending agents.
Ø
They are aqueous solutions of natural and synthetic
gums.
Ø
It is
applicable only to deflocculated

suspensions.
E.g. methyl cellulose, sodium carboxy methyl
cellulose,
acacia, gelatin and tragacanth.
Ø
These structured vehicles entrapped the particle and
reduces the sedimentation
of particles.
Ø
Thus, the use of deflocculated particles in a structure
vehicle may form
solid hard cake upon
long storage.
Ø
Structured vehicle is not useful for
Parenteral
suspension
because they may create problem in
syringeability
due to high

viscosity.
Structured vehicle

28. 28
28
FORMULATION OF SUSPENSIONS
INGREDIENTS FOR

29. VISCOSITY :-

30. Viscosity is a measure of a fluid's
resistance to flow
.
It describes the internal friction of a
moving fluid.
A fluid with large viscosity resists motion
because its molecular makeup gives it a
lot of
internal friction
.
A fluid with
low
viscosity
flows easily
because its molecular makeup results in
very little friction when it is in motion.

31. 31
Suspending agent are also known
as hydrophilic
colloids

which form
colloidal dispersion with Water
and increase the viscosity of the continous phase.
Ø
Suspending agent form film around particle and
decrease interparticle attraction.
Ø
Most suspending agents perform two functions
i.e. besides
acting as a suspending agent
they also
imparts viscosity to the solution.
1)
Suspending agents
Ø
Preferred suspending agents are those that give
thixotropy
to the media such as Xanthan gum,
Carageenan
Eg.
Methylcellulose, Hydroxyethylcellulose,
Carboxymethylcellulose
,
Microcrystalline cellulose, Acacia,
Tragacanth, Carbomer, Gelatin

32. SURFACE TENSION
"Surface tension is a
contractive
tendency
of the surface of a fluid
that allows it to resist an external
force."

33. FORMULA USED TO CALCULATE SURFACE
TENSION :-
Where
,
Where
,
 
γ
=
surface

tension

 
θ
=
contact

angle

 
ρ
=
density

g
=
acceleration

due

to

gravity

r
=
radius

of

tube

35. 35
35
Hydrophilic materials are easily wetted by water while
hydrophobic materials are not.
Ø
However hydrophobic materials are
not
easily
wetted by
Water (
polar liquids
)

Ø
The extent of wetting by water is dependent on the
hydrophillicity
of the materials.
Ø
If the material is hydrop
hobic then

it is
difficulty
to
w
et by water.
2)
Wetting Agents

36. 36
36
.

Surfactants decrease the interfacial tension between
drug particles and liquid thus liquid is penetrated in
the pores of drug particle displacing air from them and
thus ensures wetting.
Ø
Generally, we use
non-ionic surfactants
Ø
Polysorbate 80
is most widely used due to its
following advantages
§
It is non-ionic so no change in pH of
medium
§
No toxicity. Safe for internal use.
3)
Surfactants

37. 37
37
The commonly used solvents used are
glycerin,
polyethylene glycol and polypropylene glycol.
Ø
The mechanism by which they provide wetting is that
they are
miscible with water and reduce liquid air
interfacial tension.
Ø
Liquid penetrates in individual particle and facilitates
wetting.
4)
Solvents

38. 38
38
They are added to produce
osmotic pressure
comparable to biological fluids
when suspension is
to be intended for ophthalmic or injectable preparation.
Ø
Most commonly used osmotic agents are
Ø
dextrose,
Ø
mannitol
Ø
sorbitol.
Ø
sodium chloride,
Ø
sodium sulfate
Ø
glycerol.
5)
Osmotic Agents

39. 39
39
Ø
Naturally occurring suspending agents such as
tragacanth, acacia,
xanthan gum are susceptible to microbial
contamination.
Ø
This leads to:
§
loss in suspending activity of suspending
agents,
§
loss of color, flavor and odor,
§
change in elegance etc.
6)
Preservatives

40. 40
40
Name of
preservatives
Concentration
range
Propylene glycol
5-10%
Disodium EDTA
0.1%
Benzalkonium chloride
0.01-0.02%
Benzoic acid
0.1%
Butyl paraben
0.006-0.05% oral
suspension
0.02-0.4% topical
formulation

41. 41
41
Ø
They are added to increase patient acceptance.
Ø
Only
sweetening agent
are not capable of
complete taste masking of unpleasant drugs therefore,
a
flavoring agents are incorporated
Ø
E.g.

7)
Flavoring And Coloring Agents
Mint
Ginger
Sarsaparilla
syrup
Anise oil
Glucose
Spearmint oil
Benzaldehyde
Glycerin
Thyme oil

42. 42
42
Colors are obtained from natural or synthetic sources.
Ø
Plant colors are most widely used for oral suspension.
Ø
The
synthetic dyes should be used within range
of( 0.0005 % to 0.001%)
Ø
Color aids in identification of the product.
Ø
Brilliant blue (blue)

Ø
Indigo carmine(blue
)
Ø
Amaranth (red)
Ø
Tartarazine (yellow
)
8)
Coloring agents
 

43. 43
43
 

They are used for taste masking of bitter
drug particles.
Bulk sweeteners
Sugars such as
Sucrose,

xylose, ribose, glucose,
mannose.

Sugar alcohols such as
sorbitol, xylitol, mannitol
A bulk sweeteners is used at
concentration
of 15-70 %
Artificial sweetening agents
Sodium cyclamate, Sodium saccharin,
Aspartame
9)
Sweetening Agents

44. 44
44
Humectants absorb moisture and prevent
degradation of API by moisture.
Ø
Examples of humectants most commonly used in
suspensions are propylene glycol
,
glycerol
Ø
Total quantity of humectants should be
between 0-10 % w/w.
10)
Humectants

45. 45
45
Ascorbic acid derivatives such as
ascorbic acid,
erythorbic acid,
Ø
Thiol derivatives such as
thio glycerol, cytosine,
acetylcysteine
,
Ø

Ø
Tocopherols
Ø
Butylated hydroxy anisole(BHA)
Ø
Butylated hydroxytoluene (BHT)
Ø
Sodium bi sulfite,
Ø
Sodium sulfateacetone
Ø
11)
Antioxidant

46. 46
.
Wetting agents
They are added to disperse solids in
continuous liquid phase.
Flocculating
agents
They

are added to floc the drug
particles
Thickeners
They

are added to increase the
viscosity of suspension.
Buffers
and pH adjusting agents
They

are added to stabilize the
suspension to a desired pH range.
Osmotic
agents
They

are added to adjust osmotic
pressure comparable to biological
fluid.
Coloring
agents
They are added to impart desired
color to suspension and improve
elegance.
Preservatives
They

are added to prevent microbial
growth.
External
liquid vehicle
They are added to construct
structure of the final suspension.

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Label

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Label