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1. Dosage form
Bi-phasic
Emulsion
W/O
and
O/W
Suspension
Based on
general class
Oral
suspension
External
applied
Parenterals
Based on
electro-
kinetic nature
of solid
Flocculated
and de-
flocculated
Suspension
Based on
particle size
Colloidal
Coarse
Nano-
suspension
Semisolid
dosage form
Ointment, cream,
Paste, and gels
Suppositories

2. Dr. Shahid Jami, Ph.D.
Email: shahid.jamil@knu.edu.iq
COLLEGE OF PHARMACY
B PHARM III STAGE (VI SEM)
PPH651
PHARMACEUTICALTECHNOLOGY II

3. SUSPENSIONS
PHARMACEUTICAL
SUSPENSIONS
DR SHAHID JAMIL
DEPARTMENT OF PHARMACEUTICS
E Mail ID : shahid.jamil@knu.edu.iq

4. SUSPENSIONS
Definition.
Classification.
Advantages & disadvantages.
Applications.
Theoretic consideration of suspensions.
•Sedimentation
•Brownian movement
•Electrokinetic properties
CONTENTS

5. SUSPENSIONS
Flocculated and deflocculated suspension
Formulation of suspensions
Preparation of suspensions
Packing of suspensions
Storage requirement & labelling
Stability problem of suspension
Evaluation of suspension
5

6. SUSPENSIONS
6

7. SUSPENSIONS
7
 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 ).
 Each phase can exist in solid, liquid, or gaseous state .
 Suspensions are heterogenous system consisting of 2
phases.
DISPERSE SYSTEM

8. SUSPENSIONS
8
A solid in liquid dispersion in which the particles are
of colloidal size.
DISPERSE SYSTEM
DISPERSED MEDIUM DISPERSED PHASE
oAqueous /oily liquid oInsoluble solid

9. SUSPENSIONS
Definition
 A Pharmaceutical suspension is a coarse dispersion in which internal
phase (therapeutically active ingredient)is dispersed uniformly
throughout the external phase.
9

10. SUSPENSIONS
 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.
 The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily
liquid for non oral use.
10

11. SUSPENSIONS
Applications
 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. Oxy tetracycline suspension
 To mask the taste of bitter of unpleasant drug.
E.g. Chloramphenicol palmitate suspension
 Suspension of drug can be formulated for topical application
e.g. Calamine lotion
11

12. SUSPENSIONS
 Suspension can be formulated for parentral application in order to
control rate of drug absorption. E.g. penicillin procaine
 Vaccines as a immunizing agent are often formulated as suspension.
E.g. Cholera vaccine
 X-ray contrast agent are also formulated as suspension .
eg: Barium sulphate for examination of alimentary tract.
12

13. SUSPENSIONS
 Oral suspension
eg: Paracetamol suspension
antacids, Tetracycline HCl.
 Externally applied suspension
eg :Calamine lotion.
 Parenteral suspension
eg: Procaine penicillin G
Insulin Zinc Suspension
Classification
Based On General Classes
13

14. SUSPENSIONS
Based on Proportion of Solid Particles
 Dilute suspension (2 to10%w/v solid)
Eg: cortisone acetate, predinisolone acetate
 Concentrated suspension (50%w/v solid)
Eg: zinc oxide suspension
14

15. SUSPENSIONS
Based on Electrokinetic Nature of Solid Particles
 Flocculated suspension
 Deflocculated suspension
15

16. SUSPENSIONS
Based on Size of Solid Particles
Colloidal suspensions (< 1 micron)
-Suspensions having particle sizes of suspended solid less than
about 1micron in size are called as colloidal suspensions.
16

17. SUSPENSIONS
Coarse suspensions (>1 micron)
Suspensions having particle sizes of greater than about
1micron in diameter are called as coarse suspensions.
 Suspensions are the biphasic colloidal dispersions of
nanosized drug particles, stabilized by surfactants.
Size of the drug particles is less than 1mm.
Nano suspensions (10 ng)
Coarse dispersion
Barium sulphate
17

18. SUSPENSIONS
Advantages And Disadvantages
.Suspension can improve chemical stability of certain drug.
E.g. Procaine penicillin G.
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
18
Advantages

19. SUSPENSIONS
 Physical stability , sedimentation and compaction can causes
problems.
 It is bulky, sufficient care must be taken during handling and
transport.
 It is difficult to formulate.
 Uniform and accurate dose can not be achieved unless
suspension are packed in unit dosage form.
19
Disadvantages

20. SUSPENSIONS
 The suspended particles should not settle rapidly and sediment
produced, must be easily re-suspended by the use of moderate
amount of shaking.
 It should be easy to pour yet not watery and no grittiness.
 It should have pleasing odour , colour and palatability.
 Good syringeability.
 It should be physically,chemically and microbiologically stable.
 Parenteral /Ophthalmic suspension should be sterilizable.
Ideal properties of Pharmaceutical Suspensions
20

21. SUSPENSIONS
Some theoretic considerations are :
Particle size control.
Wetting
Sedimentation
 Brownian movement
Electokinetic
Aggregation
21
THEORITICAL CONSIDERATION OF SUSPENSIONS

22. SUSPENSIONS
22
Particle size control:
- Particle size of any suspension is critical and must
be reduced within the range .
-Too large or too small particles should be avoided.
Larger particles will:
 settle faster at the bottom of the container
 particles > 5 um impart a gritty texture to the product
and also cause irritation if injected or instilled to the eye
 particles > 25 um may block the needle
-Too fine particles will easily form hard cake at the bottom
of the container.

23. SUSPENSIONS
23
Wetting of the particles
 Hydrophilic materials (talc, ZnO, Mg2CO3) are easily
wetted by water while hydrophobic materials (sulphur , charcoal)
are not due to the layer of adsorbed air on the surface.
 Thus, 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.
 However hydrophobic materials are easily wetted by
non-polar liquids.

24. SUSPENSIONS
THEORY OF SEDIMENTATION
SEDIMENTATION:
Sedimentation means settling of particle (or) floccules occur
under gravitational force in liquid dosage form.
24

25. SUSPENSIONS
2.1.
Velocity of sedimentation expressed by Stoke’s equation
Where,
d = Diameter of particle
r = radius of particle
vsed.= sedimentation velocity in cm / sec
ρ s= density of disperse phase
ρ o= density of disperse media
g = acceleration due to gravity
η o = viscosity of disperse medium in poise
25

26. SUSPENSIONS
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.
26

27. SUSPENSIONS
Sedimentation Parameters
27
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 / VO
Where,
Vu = final or ultimate volume of sediment
VO = original volume of suspension before settling

28. SUSPENSIONS
28
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

29. SUSPENSIONS
The sedimentation volume gives only a qualitative account of
flocculation.
Fig : Suspensions quantified by sedimentation volume (f)
29

30. SUSPENSIONS
30
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
The minimum value of ß is 1,when flocculated suspension
sedimentation volume is equal to the sedimentation volume
of deflocculated suspension.

31. SUSPENSIONS
31
Example: Compute the sedimentation volume of a 5% w/v
suspension of magnesium carbonate in water.The initial volume
isVo = 100 mL and the final volume of the sediment isVu = 30
mL. If the degree of flocculation is β =1.3, what is the
deflocculated sedimentation volume, F∞?
F =Vu /Vo
F = 30/100 = 0.3
β = F / F∞
1.3 = 0.3 / F∞
F∞ = 0.23

32. • Work must be done to reduce a solid to small particles and disperse them in a continuous medium.
• The large surface area of the particles that results from the comminution is associated with a
surface free energy that makes the system thermodynamically unstable.
• by which we mean that the particles are highly energetic and tend to regroup in such a way as to
decrease the total area and reduce the surface free energy.
• An increase in the work, W, or surface free energy, ΔG, brought about by dividing the solid into
smaller particles and consequently increasing the total surface area, ΔA, is given by
ΔG= γSL. ΔA
• where γSL is the interfacial tension between the liquid medium and the solid particles
Surface free energy

33. .
33 20
Thermodynamic and kinetic stability
of dispersed systems
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.
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).

34. SUSPENSIONS
 Brownian movement can be observed,
 If particle size is about 2 to 5mm,
 When the density of particle & viscosity of medium are
favorable.
34

35. Electrical Properties of Interfaces
35 20

36. Electrical Properties of Interfaces:
Electric double layer
2018-4-14
• Consider solid surface in contact with solution of electrolyte
containing ions
• Some cations (+) adsorb on solid surface
• Adsorbe ions that give charge to surface aa' (in this case
cations +) known as potential determining ions.
• Anions attracted to positive charge by electrical force of
attraction known as counter ions or gegenions .
• Shear plane is bb' rather than aa' because of tightly bound layer
• First layer is aa' to bb'
• Second layer is bb' to cc'... more negative chargr is present in this
layer in this case.

37. Electric double layer
2018-4-14

38. Nerst potential
2018-4-14
• Potential at solid surface due to aa' due to
potential determining ions is known as nerst
potential
• It is define as potential difference between
actual surface and electro
nutral region

39. Zeta potential
2018-4-14
Ø 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.
Ø Zeta potential has practical application in stability of systems
containing dispersed particles .

40. 26
26
 Ø If the zeta potential is reduced below a certain
value, the attractive forces exceed the repulsive
forces, and the particles come together. 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 de-flocculation
depends on zeta potential carried by particles.
Zeta potential

41. 2018-4-14
Electrokinetic potential

42. SUSPENSIONS
42
 Ø The potential at the solid surface aa′ due to the potential-determining ion is
theelectrothermodynamic (Nernst) potential, E, and is defined as the difference in potential
between the actual surface and theelectroneutral region of the solution.
 Ø The potential located at the shear plane bb′ is known as the electrokinetic, or zeta, potential,
Z. The zeta potential is defined as the difference in potential between the surface of the tightly
bound layer (shear plane) and the electroneutral region of the solution.
 As shown in Figure , the potential initially drops off rapidly, followed by a more gradual decrease
as the distance from the surface increases.
 This is because the counterions close to the surface act as a screen that reduces the electrostatic
attraction between the charged surface and those counterions further away from the surface.
 The zeta potentials are positive (Z1), zero (Z2), and negative (Z3).

43. SUSPENSIONS
43
Deflocculation and flocculation
Flocculated Suspensions
 In flocculated suspension, formed flocs (loose aggregates) will cause
increase in sedimentation rate due to increase in size of sedimenting
particles.
 Hence, flocculated suspensions sediment more rapidly.
Here, the sedimentation depends not only on the size of the flocs but
also on the porosity of flocs.

44. SUSPENSIONS
44
Deflocculated suspensions
In deflocculated suspension, individual particles are
settling.
 Rate of sedimentation is slow , which prevents
entrapping of liquid medium which makes it difficult to
re-disperse by agitation.
This phenomenon called ‘caking’ or ‘claying’.
 In deflocculated suspension larger particles settle fast
and smaller remain in supernatant liquid so supernatant
appears cloudy.

45. DLVO theory
2018-4-14
• DLVO theory was developed in the 1940s and named
after the
• Russian scientists
– B. Derjaguin
– L. Landau,
• Dutch scientists
– E. Verwey
– J. Overbeek),

46. DLVO
2018-4-14
• It proposed that an energy barrier resulting from the electrostatic
repulsive force prevents two particles approaching one another
and adhering together.
• If the particles collide with sufficient energy to overcome the barrier,
• the Van der Waals attractive force will attract them strongly and
cause them adhere together irreversibly.
• If the particles repel each other strongly, the dispersion will
resist coagulation and the dispersed system will be stable.
• If the repulsion is not sufficient then coagulation will take place.

47. Contd...
2018-4-14

48. Flocculation curve/Secondary minimum
2018-4-14

49. Need of Controlled Flocculation
2018-4-14
• Assume powder is properly wetted and
dispersed
• In order to prevent compact sediment we
need controlled flocculation

50. Controlled Flocculation
2018-4-14
• Electrolytes (ionic substance) act as flocculating
agents by reducing electrical barrier between
particles... by decresing zeta potential and forming
bridge between adjascent particles
• Surfactant
• Polymer

51. • At low electrolyte
conc --Repulsive
force predominate
• At high electrolyte
conc --Repulsive
force reduce and
cause coagulation
Effect of electrolytes
2018-4-14

52. Bismuth subnitrate suspension
2018-4-14

53. Effect of electrolytes
2018-4-14
• Bismuth sub nitrate particles posses +ve charge
• If we add monobasic potassium phosphate
(KH2PO4) then positive zeta potential decrease to
zero because of adsorption of -ve phosphate ions
then increase in negative direction
• At certain +ve zeta potential, maximum
flocculation occur

54. Effect of electrolytes
2018-4-14
• Onset of flocculation coincide with maximum
sedimentation volume
• When zeta potential become sufficiently -ve
repeptization (deflocculation) occur once again and
sedimentation volume(F) falls

55. Effect of Surfactant
2018-4-14
• Surfactant improve dispersion by reducing
surface tension
• Act as wetting and deflocculating agent
• Ionic surfactant (SLS) sometime cause
flocculation

56. Effect of Polymers
2018-4-14
• Act as flocculating agent
• Chain of polymer adsorb on multiple particles
• Ex. Xanthum gum