Suspension for B.pharm

2.  Suspension may be defined as preparation
containing finely divided drug particles
distributed somewhat uniformly throughout a
vehicle in which the drug exhibits a minimum
degree of solubility.
or

3.  Suspensions 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.

4. • According to the particle size of the
dispersed phase, suspensions are divided
into:
Coarse suspension:
which is a dispersion of particles with a mean
diameter greater than1 µm.
 Colloidal suspension:
Which is a dispersion of particles with a mean
diameter less than 1 µm

5.  If patient has a difficulty of swallowing solid
dosage forms (a need for oral liquid dosage form).
 Faster rate of dissolution and oral absorption than
solid dosage forms, yet slower than solutions.
 Drugs that have very low solubility are usefully
formulated as suspensions.
 Drugs that have an unpleasant taste in their
soluble forms (e.g., chloramphenicol (soluble)
vs. chloramphenicol palmitate (insoluble )).

6.  Suspension should settle slowly & should be
readily redispersed upon shaking of the
container.
 The suspension is pourable.
 Particles in suspension are small and relatively
uniform in size. so that the product is free from
a gritty texture.

7.  Based on General class
→ Oral Suspension
e.g. Paracetamol Suspension
→ Externally Applied suspension
e.g. Calamine lotion
→ Parenteral Suspension
e.g. Insulin zinc suspension

8.  Based on proportion of Solid Particles
 Dilute Suspension (2 to 10% w/v solid)
e.g. cortisone acetate, predinsolone
acetate
 Concentrated Suspension (50% w/v solid)
e.g. Zinc oxide suspension

9.  Based on electrokinetic nature of Solid
particle
 Flocculated Suspension
 Deflocculated Suspension

10.  Based on Size of Particle
 Coarse Suspension
Suspensions having particle sizes of greater
than about 1micron in diameter are called as
coarse suspensions.
 Colloidal Suspension
Suspensions having particle sizes of
suspended solid less than about 1micron in
size are called as colloidal suspensions.

11.  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 redisperse easily & reform the original
suspension.
 Flocculated suspensions not be elegant because
they are difficult to remove from bottles or vials &
on transferring from the bottle the floccules
remaining sticking to the side of the bottle.

12.  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 redisperse easily & form the cake.
 Deflocculated suspensions be elegant. They
have pleasing appearance bec. the substance
remain suspended for sufficient long time.

15.  It is defined as the formation of a
nonredispersible sediment within a suspension
system.
 CAUSES: Crystal bridging & closed aggregate in
formulation.
 In crystal bridging, particle surface crystal
growth occurs on two or more particles
simultaneously in the steady formation.

16.  Small changes in temperature that occurs during
shelf storage lead to unexpectedly rapid caking
via crystal bridging.
 A sedimented, highly coagulate suspension tends
to form large coagules as the surface films
present on coagulated particle causes the filmed
particles to cling to each other.

17. SEDIMENTATION:
Sedimentation means settling of particle (or)
floccules occur under gravitational force in
liquid dosage form.

18.  Stokes equation:
d = Diameter of particle
r = radius of particle
V sed.= sedimentation velocity in cm / sec
ρs= density of disperse phase
ρo= density of disperse media
g = acceleration due to gravity
ηo= viscosity of disperse medium in poise

19.  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.

20.  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.

21. Brownian movement can be observed,
 If particle size is about 2 to 5µm,
 When the density of particle & viscosity of
medium are favorable.

22.  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.
SURFACE
Tightly bound layer
Electroneutral
region

23.  As the potential drops off rapidly at first, followed more
gradual decrease as the distance from the surface
increases.
 This is because the counter ions close to the surface acts
as a screen that reduce the electrostatic attraction
between the charged surface and those counter ions
further away from the surface.

24.  Zeta potential has practical application in stability
of systems containing dispersed particles .
 Since this potential, rather than the Nernst
potential, governs the degree of repulsion
between the adjacent, similarly charged,
dispersed particles.
 If the zeta potential is reduced below a certain
value , the attractive forces exceed the repulsive
forces, and the particles come together.

25. Zeta Potential (mV) Stability behavior of Colloid
From 0 to ±5, Rapid Coagulation or flocculation
From ±10 to ±30 Incipient instability
From ±30 to ±40 Moderate stability
From ±40 to ±60 Good stability
More than ±61 Excellent stability

26.  Structured vehicle also called as thickening agent
or suspending agent.
 They increases the viscosity of the continuous
phase so that the particles remain suspended for
a sufficient long time.
 These structured vehicles entrapped the particle
and reduces the sedimentation of particles.
 Although, these structured vehicles reduces the
sedimentation of particles.

27.  Acacia, Tragacanth & sodium alginate not very
commonly used.
 The semi-synthetic structured vehicles are
widely used.
 E.g. methyl cellulose, CMC, hydroxypropyl
methyl cellulose etc.
 Clays such as hydrated aluminium silicate or
magnesium silicate also used as thickening
agent.

28.  Wetting agent or substance which reduce the
interfacial tension between the solid particle &
liquid phase.
 It is adsorbed at the solid/liquid interface, in such
way that the affinity of the particles for the
surrounding medium is increased & interparticular
forces are decreased.

29.  The particles, even high density, float on the
surface of the liquid until the layer of air is displaced
completely.
 The use of wetting agent allows removing this air
from the surface and to easy penetration of the
vehicle into the pores.
 e.g. alcohol in tragacanth mucilage, glycerin or
glycol in sodium alginate etc.
 Excessive amount wetting agent lead to foaming or
undesirable taste or odour to suspension.

30.  Flocculating agent or surfactant are reduces the
interfacial tension.
 They act like, surfactant with negative charge
are adsorbed on the particles, minimise
flocculation in the presence of positive ions
because of natural repulsion of like charge.

31.  e.g. of negative charge surfactant sodium
lauryl sulphate, sodium dioctyl sulphocinate
etc.
 Non-ionic surfactant also have negative
charge surfactant in solution.
 Tweens, carbowaxses are frequently used.

32.  Some particles have not sufficient surface
energy, so that particles come together & forms
large particle.
 To overcome that difficulty the substance may
be introduced in the suspension & those called
dispersing agent.

33.  These substance increase the zeta potential &
do not allow the particles to come together to
form large particles.
 They also act as stabiliser in suspension.
 e.g. glyceryl monostearate, polyoxethylene
glycol, sorbitan etc.

34.  It should effective against wide range of micro-
organisms.
 It should be physically & chemically stable.
 It should be non-toxic & compatible with other
added substance.
 e.g. benzoic acid, sodium benzoate, methyl &
propyl paraben.

35.  Suspension Containing Diffusible Solids
 Suspension Containing Indiffusible Solids
 Suspension Containing Poorly Wettable Solids
 Suspension Produced by Chemical Reaction

36.  Some insoluble solids are light & easily
wettable.
 On that reason, they readily mix with water &
on shaking, diffuse through the liquid for long
enough to ensure even distribution in each
dose.
 Such substance are known as diffusible or
dispersible solids.

37.  List of diffusible solids commonly used in oral
preparations
Calcium Carbonate..antacid
Light Kaolin…treat diarrhea
Light Magnesium Carbonate..laxative
Magnesium Trisilicate…antacid
Rhubarb Powder…digestive problems

38.  Finely powder
 Take insoluble powder in a mortar.
 Add sufficient vehicle to produce smooth paste.
 Add any non-volatile solid ingredients in part of
the vehicle, and mix well.
 Add any volatile solid ingredients, previously
dissolved in some of the vehicle & mix well.
 Add any liquid ingredients.

39.  Rinse the mortar & pestle with successive
volume of vehicle until they are quiet clean,
transferring the rinsing to the bottle.
 Make up to the volume with vehicle & shake
thoroughly.
 CONTAINER & STORAGE:
 Dispensed medicines i.e. mixture, lotion etc.
 Thick container with wide mouth.
 Store in cool place.
 Very low temp. May cause suspended
particles to aggregated

40.  Indiffusible particles will not distributed in a vehicle
long enough.
 So that the correcting this problem is to increases
the viscosity of the vehicle by adding a thickening
agent.

41.  Used Internally Indiffusible solids
Aspirin..fever & pain
Chalk..antacid
Phenobarbiton..sedative
Sulphadimidine…chalmydia
 Used Externally Indiffusible solids
Calamine..pain & itching
Hydrocortisone..inflammation
Sulphur..antibacterial
Zinc oxide..irritation

42.  Tragacanth powder mainly used suspending
agent for that type of preparation.
 Tragacanth powder is used in the ratio of 2 gm
per 100 ml of the suspension.
 Tragacanth mucilage it is used in the ratio of ¼
th of the volume of the suspension.

43.  Tragacanth mucilage is used only when the
vehicle is chloroform water or water.
 Bec. If it added to preparations containing a
medicinally active vehicle, the mucilage replace
medicinally active vehicle, there by decreasing
their activity.
 In such cases tragacanth powder must be used
as suspending agent.

44.  Finely powder the Indiffusible solid particles
take in a mortar.
 Add any diffusible or soluble solids.
 Add tragacanth powder or mucilage & mix
thoroughly.
 If only Indiffusible substance is to be
incorporated, mix it with tragacanth powder in a
mortar.
 Add sufficient vehicle to produce smooth
cream.
 Then add more vehicle to make up the final
volume.

45.  Some substance e.g. sulphur & hydrocortisone
are both insoluble in water & poorly wetted by
it.
 Those are produce clumps & it is difficult to
disperse in aqueous liquids.
 Also produce foam on shaking because it is
satbilised by the film of unwettable solid at the
liquid /air interface.

46.  On that reason added satisfactory wetting agent,
those must be reduced the interfacial energy
between the solid & liquid.
 Those agent adsorbed at the solid/liquid interface
in such a way that the affinity of the particles for
the surrounding medium is increased, while the
interparticular forces are decreased.
 e.g. alcohol in tragacanth mucilage, glycerin &
glycol in sodium alginate, Quillaia extracts have
been used in sulphur lotion etc.

47.  Chemical reaction method are used to produce
insoluble active constituents in the lotion.
 In that method highly diluted solutions of
reacting substance are mixed together.
 So as to form very finely divided precipitates that
can be easily distributed throughout the liquid on
shaking.

48.  Precipitates so formed are generally diffusible
in nature therefore no need any suspending
agent.
 Zinc sulphide lotion B.P.C produced by this
method.

49.  Pharmaceutical suspensions for oral 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.

50.  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.

51. LABEL:
 Shake well before use
 Do not freeze
 Protect from direct light(for light sensitive
drugs)
 In case of dry suspensions powder the
specified amount of vehicle to be mixed may
indicated clearly on label.

52. STORAGE:
 Suspensions should be stored in cool place
but should not be 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
0c

53. Dispersion system is defined as a
heterogenous two phase system in which
internal (dispersed, discontinous ) phase is
distributed or dispersed within the
continuous (external) phase or vehicle.
e.g. Suspensions & Emulsions

54. PROPELLER MIXERS
 The most often used mixing implement is
marine propeller mixer.
 These machines use rounded, pitched, three
blade design that produces mostly axial flow.
 They provide good flow and blending
capabilities in small batches of low to
medium viscosities.

55.  Propellers mixers can be installed on vertical
centerline or through the side wall of process
vessel.
 They can be operated at around 300-400rpm.
 These are used mostly for liquid-liquid blending
applications in some easily producible
suspensions.

57.  The most versatile of all mixers in the
entire span of mixing equipments are the
axial and radial flow turbines.
 Turbines mixers can be made to handle
huge batches, even up to 5,00,00gal &
suitable for emulsification process.

58. Radial Flow turbine
Axial flow turbine

59.  It is also called as saw blade disperser.
 This machine consists of a variable speed
shaft connected to an impeller with a serrated
edge.
 The tip speed is set around 4000 ft/min.
 The diameter of impeller should be 1/3 of
diameter of vessel.

60.  The impeller should be located one impeller
diameter off the bottom of vessel
 It can deagglomerating particles when the
viscosities between 10,000 to 20,000cps.
Application:
It is used for pigment dispersion, dye stuffs

61. Limitations:
 Air incorporation is another problem so it is
best used for suspensions and not for
emulsions.

62.  It is used to disperse the solids into liquids and
to emulsify liquid-liquid systems.
 These generally used as polishing machines for
emulsions or suspensions because they
produce fine particle or droplet size product to
enhance a products stability.
 They are operated at speed of 3600 rpm

64. Types:
1. Triple roll mill
2. Ball mill

65. A three roll mill or triple roll mill is a
machine that uses shear force created by
three horizontally positioned rolls rotating in
opposite directions and different speeds
relative to each other, in order to mix, refine,
disperse, or homogenize viscous materials
fed into it.
TRIPLE ROLL
MILL

67.  It is used for size reduction fine solid discrete
particles or for deagglomeration of very tightly
bound agglomerates.
 The machine consists of cylindrical drum into
which a charge of heavy spherical balls usually
metal or ceramic is loaded along with the
components of the dispersion.

69.  SEDIMENTATION METHOD
The suspension formulation(50mL)was poured
separately into 100mLmeasuring cylinders and
sedimentation volume was read after 1,2,3 and
7days, and there after at weekly intervals for
12weeks.

70. Sedimentation volume was calculated
according to the equation:
F =Vu/Vo
Where , F = sedimentation volume
Vu = ultimate height of sediment
Vo = initial height of total suspension

71.  The stability of suspension depends on the
particle size of the dispersed phase.
 Change in the particle size with reference to time
will provide useful information regarding the
stability of a suspension.
A change in particle size distribution and crystal
habit studied by
 microscopy
 coulter counter method

72.  Rapid processing of photo micrographs is
enhanced by attaching Polaroid camera to the
piece of monomolecular microscope.
 By using this photo micrographs we can
determine the changes in physical properties
and stability of suspensions.

74.  pH MEASUREMENT
 VISUAL INSPECTION
With visual inspection, the ingredients and the
final products are carefully examined for
purity and for appearance .