1. Suspension
Hindu College of Pharmacy
Sonipat(131001)
Guided by
Dr. Dinesh Kaushik
Associate professor
Hindu College of
Pharmacy Sonipat
Presented by
Vikash
M-Pharmacy(1st Sem)
Modern Pharmaceutics
Roll no. 8-M/2019
3. Definition
Suspension may be defined as preparation
containing finely divided drug particles distributed
uniformly throughout a vehicle in which the drug
exhibits a minimum degree of solubility.
or
4. Suspension are the biphasic liquid dosage form of
medicaments in which the finely divided solid particles.
The range of solid particles in suspension from 0.5 to
5.0 micron.
Suspensions are used in orally, parentally and also
externally.
They are chemically stable than solution.
5. Properties of good Suspension:
Suspension should settle slowly & should be readily re-
dispersed upon shaking of the container.
The suspension is pourable.
Particle in suspension are small and relatively uniform
in size. So that the product is free from a gritty texture.
6. Advantages of suspensions:
Suspension can improve chemical stability of certain
drug. Ex. Procaine penicillin G
Drug in suspension exhibits higher rate of
bioavailability than other dosage forms.
Bioavailability is in following order:
Emulsion>Suspension>Capsule>Compressed
tablet>Coated tablet
Duration and onset of action can be controlled. Ex.
Protamine Zinc-insulin suspension.
Suspension can mask the unpleasant/bitter taste of
drug. Ex. Chloramphenicol palmitate.
7. Disadvantage:
Physical stability, sedimentation and compaction can
cause problems.
It is bulky, therefore sufficient care must be taken
during handling and transport.
It is difficult to formulate.
Uniform and accurate dose can not be achieved unless
suspension unless suspension are packed in unit dosage
form.
8. Pharmaceutical Application of Suspension
Suspension is usually applicable for drug which is insoluble
or poorly soluble. E.g. Prednisolone
Suspension to prevent degradation of drug or to improve
stability of drug. E.g. Oxytetracycline suspension.
Suspension of drug can be formulated for topical
application. E.g. Calamine lotion.
To mask the taste of bitter or unpleasant drug when
formulated in solution form.
Bulky, insoluble powders can be formulated as a
suspension so that they are easier to take. E.g. Kaolin or
chalk.
9. Internal phase:
The internal phase consisting of insoluble solid particles
having 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.
External phase:
The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily liquid
for non oral use.
10. Classification:
Based on General class
I. Oral suspension
e.g. Paracetamol suspension, antibiotic
II. Externally applied suspension
e.g. calamine lotion
III. Parenteral suspension
e.g. Insulin zinc suspension
11. Based on nature of solid particle:
Flocculated suspension
Deflocculated suspension
Based on proportion of Solid Particles:
Dilute Suspension (2 to 10% w/v solid
e.g. cortisone acetate.
Concentrated Suspension (50% w/v solid)
e.g. Zinc oxide suspension
12. • According to particle size of the dispersed phase,
suspensions are divided into:
Coarse suspension: Which is a dispersion of particles
with a mean diameter greater than 1 µm.
Colloidal suspension: Which is a dispersion of
particles with a mean diameter less than 1 µm.
13. Flocculated system
In flocculated system the individual particle are contact
with each other to form loose aggregate & create
network like structure.
Rate of sedimentation is high.
Sediment is loosely packed. When shaking it can be re-
disperse easily & reform the original suspension.
Flocculated suspensions not be elegant because they
are difficult to remove from bottles & on transferring
from the bottle the floccules remaining sticking to the
side of the bottle.
14. De-flocculated or Non-flocculated
system
In deflocculated system the individual particle are exist
as separate entities.
Rate of sedimentation is low.
Sediment is tightly packed. When shaking it can not be
re-disperse easily & form the cake.
Deflocculated suspensions be elegant. They have
pleasing appearance because the substance remain
suspended for sufficient long time.
15. Difference between flocculated and
deflocculated suspension
Flocculated Deflocculated
1. Particles forms loose aggregates and
form a network like structure.
1. Particle exists as separate entities.
2. Rate of sedimentation is high. 2. Rate of sedimentation is low.
3. Sediment is rapidly formed. 3. Sediment is slowly formed.
4. Sediment is loosely packed and
doesn’t form a hard cake.
4. Sediment is very closely packed and
a hard cake is form.
5. Sediment is easy to re-disperse. 5. Sediment is difficult to re-disperse.
6. Suspension is not pleasing in
appearance.
6. Suspension is pleasing in
appearance.
7. The floccules stick to the sides of the
bottle.
7. They don’t stick to the sides of the
bottle.
16.
17. Theory of sedimentation
SEDIMENTATION:
Sedimentation means settling of particle (or) floccules
occur under gravitational force in liquid dosage form.
18. DLVO Theory
The scientists Deryaguin, Landau, Vervey and Overbeek
developed a theory in the 1940s which dealt with the
stability of colloidal systems.
DLVO theory suggests that, the stability of a colloidal
system is determined by the sum of the Vander Waals
attractive (VA) and electrical double layer repulsive (VR)
forces that exist between particles as they approach each
other due to the Brownian motion they are undergoing.
The Vander waal forces depend on chemical nature and
size of particle. The electrostatic repulsive forces depend
on density, surface charge and thickness of double layer.
19. Methods for stabilizing suspension
Physical Stability can be achieved by maintaining the
particle in Brownian motion
a) Provide Electric charge on surface of dispersed
particle: The like charge on the particles will prevent
these coming closer together and thus maintaining a
Brownian motion.
b) Maintain solvent sheath around the particle: The
solvent layer prevent the particle coming closer and also
maintain Brownian motion.
20. Stoke ’s equation
Where V sed. =sedimentation velocity in cm/sec
d=diameter of particle
rs=density of disperse phase
ro=density of disperse media
g= acceleration due to gravity
h=viscosity of disperse medium in poise
21. 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)
Particles which freely settle without collision .
Particles with no physical or chemical attraction.
22. Brownian movement
Brownian movement of particle prevents
sedimentation by keeping the dispersed material in
random motion.
Brownian movement depends on the density of
dispersed phase and the density and viscosity of the
disperse medium
Brownian movement can be observed
If particle size is about 2 to 5µm,
When the density of particle & viscosity of medium are
favorable.
23. Formulation of suspensions:
Wetting agents: They are added to disperse solids in
continuous phase. Ex: polysorbate 80,20, span etc.
Suspending agents: They are added to flocs the drug
particles.
Thickeners: They are added to increase the viscosity of
suspension. Ex: gaur gum, xanthan gum.
Buffers and pH adjusting agents: They are added to
stabilize the suspension to a desired pH range.
Coloring agents: They are added to impart desired color to
suspension and improve elegance.
Preservative: They are added to prevent microbial growth.
e.g. benzoic acid, sodium benzoate, methyl & propyl
paraben.
24. Preparation of suspension
Step 1:
Suspensions are prepared by grinding the insoluble materials in the
mortar. To a smooth paste with a vehicle containing the wetting agent.
Step 2:
All soluble ingredients are dissolved in same portion of the vehicle and
added to the smooth paste to step1 to get slurry.
Step 3:
The slurry is transformed to a graduated cylinder, the mortar is rinsed
with successive portion of the vehicle.
25. Step 5 :
Make up the dispersion to the final volume .
Thus suspension is prepared.
Step 4: Decide whether the solids are
• Suspended in a structured vehicle.
• Flocculated
• Flocculated and then suspended
Add the vehicle containing the suspending agent (or)
flocculated agent
26. Packing of Suspension:
Pharmaceutical suspension for ideal use are generally
packed in wide mouth container having adequate space
above the liquid to ensure proper mixing.
Parenteral suspensions are packed in either glass
ampoules or vials.
27. Ideal requirements of Packaging
material
It should be inert.
It should effectively preserve the product from light,
air, and other contamination.
It should effectively deliver the product without any
difficulty.
It should be cheap.
29. Sedimentation method:
Two parameters are studied for determination
of sedimentation.
Sedimentation volume.
Degree of flocculation.
30. Sedimentation volume
The suspension formulation(50ml) poured separately
into 100ml measuring cylinders and sedimentation
volume was read after 1,2,3 and 7days, and there after
at weekly interval for 12 weeks.
Triplicate results obtained for each formulation.
Sedimentation volume calculated according to the
equation:
F=Vu/Vo
Where, F=sedimentation volume,
Vu=ultimate height of sediment,
Vo=initial height of total suspension.
31. It is the ratio of the sedimentation volume of the flocculated
suspension , F, to the sedimentation volume of the deflocculated
suspension, F’
b=F/F’
The minimum value of b is 1, when flocculated suspension sedimentation
volume is equal to the sedimentation volume of deflocculated suspension.
Degree of flocculation (b)
b=(Vu/Vo) flocculated
(Vu/Vo) deflocculated
32. Rheological method:
It provide information about Settling behaviours.
Brookfield viscometer is used study the viscosity of the
suspension.
It is mounted on Heli-path stand using T-bar spindle.
T-bar spindle is made to descend slowly into the suspension
and the dial reading on the viscometer is then a measure of
the resistance the spindle meets at various level.
This technique also indicates at which level of the suspension
the structure is greater owing to particle agglomeration.
33. Brookfield viscometer
Apparatus
In the screening study, good
suspension show a lesser rate of
increase of dial reading as the spindle
turns, that is , the curve is horizontal
for a longer period.
34. Electrokinetic method
Measurement of Zeta-potential using Micro
electrophoresis apparatus & Zeta Plus (Brook haven
Instruments Corporation , USA)
It shows the stability of a disperse system.
Zeta PlusMicro electrophoresis apparatus
35. Electrokinetic method
Zeta Potential: The zeta potential defined as the
difference between the surface of the tightly bound layer
(shear plane) & the electroneutral region of the solution.
Zeta potential has practical application in stability of
systems containing dispersed particles.
If the zeta potential is reduced below a certain value , the
attractive forces exceed the repulsive forces, and the
particles come together.
36.
37. Factors that contribute to appreciable stability of a
suspension include:
Small particle size: reduce the size of the dispersed
particle increases the total surface area of the solid.
Greater the degree of subdivision of a given solid the
larger the surface area.
Increase in surface area means also an increase in
interface between the solids and liquids leading to an
increase in viscosity of a system.
Stability of suspension
38. Increasing the viscosity- increasing the viscosity of
the continuous phase can lead to the stability of
suspensions.
Rate of sedimentation can be reduced by increase in
viscosity.
Viscosity increase by addition of thickening agents to
the external phase
Rate of release of a drug from a suspension is also
dependent on viscosity.
Temperature-
Another factor which negatively affects the stability of
suspension is fluctuation of temperature. Temperature
fluctuation can lead to caking and claying
39. Storage requirements & labelling
Label:
Shake well before use.
Do not freeze.
Protect from direct sunlight (for light sensitive drugs).
In case of dry suspensions powder the specified amount of
vehicle to be mixed may be indicated clearly on label.
Storage:
Suspension should be stored in cool place but should not
kept in a refrigerator.
Freezing at very low temperatures should be avoided which
may lead to aggregation of suspended particles.
Stored at controlled temperature from 20-25 oC .
41. Nano suspension
Nano suspensions are the biphasic colloidal dispersions
of nanosized drug particles stabilized by surfactants
without the matrix materials.
They can also be defined as a biphasic system consisting
of pure drug particles dispersed in an aqueous vehicle
in which the diameter of the suspended particle is less
than 1 μm in size.
They have average diameter of particle 200-600nm.
42. Taste masked pharmaceutical suspension
Un-palatability due to bad taste is a major concern in most
of the dosage forms containing bitter drugs.
In case of suspensions also taste masking is being applied
to mask bitterness of drugs formulated.
The taste masking approaches for suspensions are:
• Polymer coating of drugs.
• Encapsulation with basic drugs.
• Coating and pH control.
43. Polymer Coating of Drugs: The polymer coat allows the
time for all of the particles to be swallowed before the
threshold concentration is reached in the mouth and the
taste is perceived.
• The polymers used for coating are
Ethyl cellulose
Eudragit RS 100
Eudragit RL 100
Eudragit RS 30 D
Eudragit RL 30 D
44. Encapsulation with a Basic Substance: Here a basic
substance is mixed with a bitter tasting drug which is
insoluble at high pH.
• The mixer is then encapsulated with a polymer
(cellulose derivative, vinyl derivative or an acid soluble
polymer
Example: copolymer of dimethyl ammonium methyl
methacrylate).
The drug after encapsulation are suspended, dispersed
or emulsified in suspending medium to give the final
dosage form.
45. Coating and pH control: Those drugs which are soluble at
high pH are preferably be maintained in a suspension at a
low pH where the drug exhibit maximum insolubility.
Similarly drugs which are soluble at low pH are preferably
maintained in suspension at a high pH where the drug is
insoluble.
Also applying polymeric coating to the drug substance
avoids solubilization of drug when administered providing
taste masking.
46. Some Examples of Taste Masked Suspensions
Sr.no Name of the drug Taste masking approach
1. Risperidone pH control and polymer coating (with Eudragit
RS)
2. Diclofenac Polymer coating with Eudragit RS 100
3. Levofloxacin Polymer coating ( Eudragit & cellulose acetate,)
47. Sustained release suspension
Sustained release is a method to increase only the duration
of action of drug being formulated without affecting onset of
action.
In suspension sustained release affected by coating the drug
to be formulated as suspension by insoluble polymer coating.
The polymer coating provides sustained release and also
masks the taste of the bitter drug.
The polymer used for sustained release in suspension is as
follows as: Ethyl cellulose, Eudragit, Cellulose acetate, etc.
The main advantage of sustained release suspension is
decrease in dosing frequency