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Pharmaceutical
Suspensions
1
CONTENTS
• What are Suspensions?
• Properties of suspension
• Types of suspensions
• Suspending agents and their classification
• Preparation of suspension
• Suspension Stability
2
Suspensions: syllabus
4
SUSPENSION-ATYPE OF DISPERSION
Coarse
Dispersion
Emulsion
Suspension
Suspension
“Preparation containing finely divided drug
particles (Suspensoids/ Dispersed phase)
distributed somewhat uniformly throughout a
vehicle (Dispersion medium) in which the
drug exhibits minimum degree of solubility”
• Suspensions are heterogeneous system
consisting of 2 phases.
• Oral suspensions are oral liquids
containing one or more active ingredients
suspended in a suitable vehicle.
• Particles size=1-50 µm 4
Suspensions
Reasons For Suspension
1. Stability; Drugs that are chemically unstable in solution but stable
when suspended. (e.g. certain antibiotics the suspensions of which are
prepared just prior to the dispensing of the preparation, extemporaneous
preparations)
2. Being a Liquid dosage form (ease of swallowing and dosing
flexibility)
3. Taste masking of disagreeable tasting drugs (e.g. Erythromycin
Estolate Oral Suspension USP, Chloramphenicol Suspension)
4. To achieve sustained release effect, where drug is encapsulated in a
suitable polymer, which is then suspended in a suitable vehicle
5
Suspensions: Importance
Ideal characteristics of Suspension
1.Settle/ sediment slowly and redisperse readily on shaking
2.Easily pourable from its container (Not too viscous)
3.Particle size should remain constant throughout long periods of
undisturbed standing
4.Therapeutic efficacy
5.Chemical stability, Elegancy etc
6
Suspensions: Properties
7
TYPES OF SUSPENSION
e.g. Zinc Insulin suspension
e.g. Calamine lotion
, Rectal Suspension
8
Oral
Suspension
1. Ready-to-use
„Oral Suspensions‟
2. Dry Powder/ Powder
for Reconstitution
„For Oral Suspensions‟
• Brufen® (Ibuprofen; anti-pyretic
etc.)
• Mucaine® (antacid;
oxethazaine+aluminium
hydroxide +magnesium
hydroxide)
• Antibacterial (Augmentin®;
combination of Amoxicillin
+ Clavulanic acid)
9
Some Oral Pharmaceutical Suspensions…
10
11
Once reconstituted, AUGMENTIN should be
stored in a refrigerator (at 2°C to 8°C) but not
frozen and used within 7 days.
12
Barium sulfate
• Radio opaque agents
• Diagnostic aids
• Oral/Rectal
• Different % w/v for different studies, like
x-ray scans, computerized tomography
(CT) scans, and other GI examinations
Packaging and Storage of suspensions
• Wide mouth containers
• Airspace for shaking
• Stored in tight containers
• Protected from freezing, excessive light and heat
• Product-specific cautions (or additional labelling requirements):
„Shake well before use‟
will need to be added to the label as the product is a suspension and will need
shaking before use to ensure accurate dosing
13
Important considerations for
suspensions
14
Ingredients For Preparation Of
Suspension
Following are the additives which are generally used in the formulation of suspensions;
1. Flocculating agents (Tweens, Spans, Carbowaxes, Sodium lauryl sulphate, Sodium
dioctyl sulphosuccinate)
2. Suspending agents (Thickening agents)
3. Wetting agents (Alcohol, Glycerin and glycols)
4. Preservative (benzoic acid, sodium benzoate, methyl paraben and propyl-paraben)
5. Organoleptic additives (Colorants, flavorants)
Flocculating agents
When formulating suspension it must be ensured that the particles are well
dispersed in the vehicle which can be improved by adding a suitable
surfactant
Generally non-ionic surfactants are used for dispersing the insoluble
particles, but anionic surfactants can also be used.
Example:
 NON-IONIC surfactants (Tweens, Spans, Carbowaxes)
 ANIONIC surfactants (sodium lauryl sulphate [SLS], sodium
dioctyl sulphosuccinate)
 Polymers e.g. bentonite clay
15
2. SuspendingAgents
• The suspending agents are used to stabilize the suspensions
• Also called thickening agents.
• A suspending agent is intended to increase the viscosity of
the vehicle and therefore slow down settling of dispersed
particles (sedimentation rates). This outcome could also be
achieved by decreasing the particle size of the powder in
suspension.
• The amount of suspending agent used in any given
formulation depends on the volume of vehicle being
thickened. 16
Suspending agents
17
Increase the viscosity of the continuous phase so that the particles remain
suspended for sufficiently long time and it becomes easy to measure the
accurate dose.
 Natural thickening agents are not widely used due to their susceptibility to
microbial attack. Hence, the semi-synthetic agents are more widely used.
Examples:
Natural Thickening agents (Acacia, Tragacanth, sodium alginate)
Semi-synthetic Thickening agents (Methyl cellulose [MC], Carboxy
methyl cellulose [CMC], Hydroxy propyl methyl cellulose [HPMC],
Sodium carboxy methyl cellulose [3.5%] is used in injectable
suspensions)
Clays (hydrated aluminium silicate, magnesium silicate)
Non-ionic substances such as sorbitol, glycerin, sugar or polyethylene
glycol [PEG] may be included to adjust the viscosity of the medium.
Wetting agents
These are the agents that reduce the interfacial tension
between the solid particles and the liquid medium by
adsorbing at the solid/liquid interface, thus producing a
suspension of desired quality.
Examples:
Alcohol in tragacanth mucilage,
Glycerin and glycols in sodium alginate or bentonite
dispersions,
Polysorbates in oral and parenteral suspensions 18
Preservative
Presence of suspending agents and medicaments which are
liable to bacterial growth make it necessary to incorporate a
preservative in a suspension.
An effective preservation should be non-toxic, effective
against a wide range of micro-organisms, should be stable and
compatible with other ingredients of the formulation.
Examples:
 Benzoic acid, sodium benzoate, methyl paraben and
propyl-paraben 19
Organoleptic additives
Coloring, sweetening and flavoring agents are used in oral
suspensions.
Similarly, colors and perfumes are incorporated in
suspensions meant for external applications but these must
be compatible with other ingredients.
20
21
Preparation Of Suspension
1
Simple Dispersion
2
Precipitation of solid from solution
22
Suspensions are prepared by grinding (or) levigating the
insoluble materials in the mortar to get a smooth paste
with a vehicle (containing the wetting agent if required)
All soluble ingredients are dissolved in portion of the
vehicle and added to the smooth paste to get slurry.
(a semi-liquid thin mixture, of insoluble substance)
The slurry is transformed to a graduated cylinder,
the mortar is rinsed with successive portion of the
vehicle.
Add the vehicle containing the suspending agent
(or) flocculating agent depending upon the type of
final product desired.
Make up the dispersion to the final volume
1. Simple Dispersion
SUSPENSION
23
1
• Change of pH: if the pH of the medium is
changed, the material which was previously soluble
at a certain pH, now separates out in fine particles
and form suspension
2
• Double Decomposition: Not applicable for
pharmaceutical purpose
3
• Change of solvent: Solids show different solubility
in different solvents. Chloramphenicol suspension
is made by this process.
2. Precipitation of solid from solution
Extemporaneous compounding of suspensions
(Extemporaneous Suspensions)
“the Extemporaneous dispensing of solid dosage
form in liquid form”
• Such suspensions are prepared just before dispensing to the patient
who are unable to swallow the solid dosage form
• Mostly in Neonates
• Preparation: Crush – Paste – Liquid
• Example: Prednisolone suspension, Ketoconazole suspension
24
Physical Stability of Pharmaceutical
Suspension
“Condition in which particles do not aggregate and
remain uniformly distributed throughout the
dispersion”
• This means that if the particles do settle they should be easily
resuspended by moderate amount of agitation
25
Factors affecting Suspension Stability
Stability of suspension depends upon:
26
1. Rate of sedimentation
2. Physical features of Dispersed Phase
3. Features of Dispersion medium
4. Addition of Flocculating Agents
5. Reconstitution of suspension
1. Rate of Sedimentation
• Sedimentation: “settling of particles or floccules due to
gravity in liquid dosage forms”
• Various factors are involved in rate of settling of particles of a
suspension which are represented by Stoke‟s Equation.
• Stoke‟s equation gives an indication of the factors that can be
adjusted to decrease the rate of sedimentation of the
formulation.
27
28
Stoke‟s Equation
ηՕ
• ρ = „rho‟
• η= „eta‟
• Unit of viscosity 
Poise= 1 g/cm.sec or
pascal sec where
1 Ps= 10P
• Large size of particle, higher rate of sedimentation or
sedimentation velocity [v ∝ d ]
• higher density of particles, higher rate of sedimentation [v ∝
ps]
• Higher viscosity of the medium, lower rate of sedimentation
[v ∝ 1/ŋ]
29
2
2. Physical features of the Dispersed phase
• Properties of suspended particles (suspensoids) and dispersion medium
should be considered
I. Nature of suspensoid
a) Easily Wettable or
b) Non-wetting; due to the presence of layer of adsorbed air on the
surface, hence forms Clump (Alcohol, Glycerin, Propylene glycol as
wetting agent)
The use of wetting agent allows to remove this air from the surface
and to easy penetration of the vehicle into the pores. The agent flows
into the voids between the particles to displace the air and reduce
liquid air interfacial tension so that water can penetrate and wet the
individual particles.
30
2. Physical features of the Dispersed phase
II. Particle size
• Probably the most concern thing is the size of particles in suspensions
• In good suspensions , the particle diameter is 0.5 to 50 𝛍𝐦
• Reduced particle size produces slow, more uniform rate of settling
• Particle size reduction is generally accomplished by dry milling (Milling=
grinding with a rotating tool) prior to incorporation of the dispersed phase into the
dispersion medium
• Micropulvenizers (high speed impact mills) or jet mills (high speed air
streams in confined space), spray dryer (solution is sprayed, air dries it)
31
Physical features of the Dispersed phase
II. Shape of particles
• Barrel-shaped or spherical:
Symmetrical barrel-shaped
particles of calcium carbonate produced more
stable suspensions , they do not form cake on
standing.
• Needle-shaped:
Needle shaped are less stable
because they form tenacious cake on standing that
could not be redistributed
32
• Suspensions are physically unstable systems due to particle-
particle interaction
• This can result in rigid cohesion of particles of suspension which
leads to the formation of a cake (agglomeration of particles into
larger masses) .
• This can ultimately result in suspension instability!
33
34
One simple method of preventing rigid
cohesion/ Caking of particles of
suspension is
“Flocculation”
“Intentional formation of a less rigid or loose
aggregation* of particles held together by weak particle
to particle bonds”
(* Floccule)
»Benefits:
Flocculated particles forming a type of lattice that resists complete settling
so are less prone to compaction than deflocculated particles.
Additional benefit: loose aggregates easily break up and readily re-
dispersed.
Flocculation
35
Flocculated & Deflocculated Suspensions
• Flocculated Suspension
“In flocculated suspensions the individual particles are in
contact with each other to form loose aggregates and create a
network like structure”
(Flocules: loose aggregates of particles by weak particle-to-particle/ Van der Waals
forces)
• Deflocculated Suspension
“In non-flocculated or de-flocculated suspensions all individual
particles exist as separate entities”
36
37
DLVO Theory
38
 DLVO theory is a
dispersion stabilizing
theory which explains
that as two particles
approach one another
their ionic
atmospheres begin to
overlap and a
repulsion force is
developed.
39
40
Zeta Potential
Zeta potential is the potential difference
between the ions in the tightly bound layer
and the electroneutral region.
Zeta potential = potential of the slipping
plane
Zeta potential governs the degree of
repulsion between adjacent, similar charged,
solid dispersed particles.
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)
41
Sedimentation Evaluation Parameters
• Two parameters are used to determine sedimentation in
suspensions:
1.Sedimentation volume “F” (Qualitative parameter)
2.Degree of flocculation “B” (Quantitative parameter)
• Sedimentation volume or „Height of sediment‟
42
43
1.
44
2.
45
Caking diagram, showing the flocculation of suspension by
means of the electrolyte
46
Flocculation zone/
(Sedimentation volume)
 this much amount
of flocculating
agent should be
added so that the
floccules can be
formed, cake
formation is
prevented.
Explanation:
 If we disperse particles of bismuth subnitrate (positively charged surface) in water, we find that
they possess a high zeta potential. Hence, because of strong forces of repulsion between adjacent
particles , the system is de-flocculated and will eventually produce a caked sediment.
 Addition of potassium phosphate: as the electrolyte is added, the anion is attracted towards
positively charged surface thus decreasing the zeta potential. Hence, now the surface charge is not
sufficient to repel the particles and suspension flocculates.
 Continuously addition: By continuous addition of electrolyte, the zeta potential falls to zero and
increases to negative side as shown in figure.
 At a certain zeta potential, maximum flocculation occurs and will persist until zeta potential has
become sufficiently negative for de-flocculation to occur once again.
 Non caking zone is the zone of balanced zeta potential.
 The onset of flocculation coincides with maximum sedimentation volume determined.
 F (sedimentation volume) remains constant while flocculation persists and only when the zeta
potential becomes sufficiently negative the sedimentation volume starts to fall.
 Finally the absence of caking in the suspensions correlates with the max sedimentation volume
,which as stated previously reflects the amount of flocculation.
 At less than maximum values of F ,caking become apparent.
47
4. FlocculatingAgents
• Controlled flocculation can be achieved by use of flocculating agents.
• Flocculating agents are added to enhance particle “re-
dispersability”
These includes
1. Polymers e.g. bentonite
2. Surfactants: non ionic (mostly used) and ionic surface–active agents
3. Electrolytes: Electrolytes acts as flocculating agents by reducing the
electrical barrier between the particles, thus, decrease the zeta
potential, this leads to decrease in repulsion potential and makes the
particle come together to form loosely arranged structure (floccules).
48
49
• Viscosity of the medium is important
which is modified to overcome the
problem of rapid sedimentation
• Suspending agents like
Carboxymethylcellulose,
Methylcellulose, Microcrystalline
cellulose, Polyvinyl pyrolidone
(PVP), xantham gum, bentonite are
few of the agents employed to
thicken the dispersion medium and
help suspend the suspensoid.
4. Features of Dispersion Medium 5. Reconstitution of Suspension
• Using the method of reconstitution
of suspension right before its use
can also keep the suspension stable
to some extent.
It is important to consider that
the suspending agent must be
inert, non-toxic, non-interacting
with the components of the
suspension and should not be in
such amount to render the
suspension too viscous to agitate
or pour.
50
Future of Suspensions
REFERENCES
• Ansel’s Pharmaceutical Dosage Forms and Drug
Delivery Systems (9th Edition)
• Tutorial Pharmacy by Cooper and Gunn’s
51

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Pharmaceutical Suspension

  • 2. CONTENTS • What are Suspensions? • Properties of suspension • Types of suspensions • Suspending agents and their classification • Preparation of suspension • Suspension Stability 2 Suspensions: syllabus
  • 4. Suspension “Preparation containing finely divided drug particles (Suspensoids/ Dispersed phase) distributed somewhat uniformly throughout a vehicle (Dispersion medium) in which the drug exhibits minimum degree of solubility” • Suspensions are heterogeneous system consisting of 2 phases. • Oral suspensions are oral liquids containing one or more active ingredients suspended in a suitable vehicle. • Particles size=1-50 µm 4 Suspensions
  • 5. Reasons For Suspension 1. Stability; Drugs that are chemically unstable in solution but stable when suspended. (e.g. certain antibiotics the suspensions of which are prepared just prior to the dispensing of the preparation, extemporaneous preparations) 2. Being a Liquid dosage form (ease of swallowing and dosing flexibility) 3. Taste masking of disagreeable tasting drugs (e.g. Erythromycin Estolate Oral Suspension USP, Chloramphenicol Suspension) 4. To achieve sustained release effect, where drug is encapsulated in a suitable polymer, which is then suspended in a suitable vehicle 5 Suspensions: Importance
  • 6. Ideal characteristics of Suspension 1.Settle/ sediment slowly and redisperse readily on shaking 2.Easily pourable from its container (Not too viscous) 3.Particle size should remain constant throughout long periods of undisturbed standing 4.Therapeutic efficacy 5.Chemical stability, Elegancy etc 6 Suspensions: Properties
  • 7. 7 TYPES OF SUSPENSION e.g. Zinc Insulin suspension e.g. Calamine lotion , Rectal Suspension
  • 8. 8 Oral Suspension 1. Ready-to-use „Oral Suspensions‟ 2. Dry Powder/ Powder for Reconstitution „For Oral Suspensions‟ • Brufen® (Ibuprofen; anti-pyretic etc.) • Mucaine® (antacid; oxethazaine+aluminium hydroxide +magnesium hydroxide) • Antibacterial (Augmentin®; combination of Amoxicillin + Clavulanic acid)
  • 9. 9 Some Oral Pharmaceutical Suspensions…
  • 10. 10
  • 11. 11 Once reconstituted, AUGMENTIN should be stored in a refrigerator (at 2°C to 8°C) but not frozen and used within 7 days.
  • 12. 12 Barium sulfate • Radio opaque agents • Diagnostic aids • Oral/Rectal • Different % w/v for different studies, like x-ray scans, computerized tomography (CT) scans, and other GI examinations
  • 13. Packaging and Storage of suspensions • Wide mouth containers • Airspace for shaking • Stored in tight containers • Protected from freezing, excessive light and heat • Product-specific cautions (or additional labelling requirements): „Shake well before use‟ will need to be added to the label as the product is a suspension and will need shaking before use to ensure accurate dosing 13 Important considerations for suspensions
  • 14. 14 Ingredients For Preparation Of Suspension Following are the additives which are generally used in the formulation of suspensions; 1. Flocculating agents (Tweens, Spans, Carbowaxes, Sodium lauryl sulphate, Sodium dioctyl sulphosuccinate) 2. Suspending agents (Thickening agents) 3. Wetting agents (Alcohol, Glycerin and glycols) 4. Preservative (benzoic acid, sodium benzoate, methyl paraben and propyl-paraben) 5. Organoleptic additives (Colorants, flavorants)
  • 15. Flocculating agents When formulating suspension it must be ensured that the particles are well dispersed in the vehicle which can be improved by adding a suitable surfactant Generally non-ionic surfactants are used for dispersing the insoluble particles, but anionic surfactants can also be used. Example:  NON-IONIC surfactants (Tweens, Spans, Carbowaxes)  ANIONIC surfactants (sodium lauryl sulphate [SLS], sodium dioctyl sulphosuccinate)  Polymers e.g. bentonite clay 15
  • 16. 2. SuspendingAgents • The suspending agents are used to stabilize the suspensions • Also called thickening agents. • A suspending agent is intended to increase the viscosity of the vehicle and therefore slow down settling of dispersed particles (sedimentation rates). This outcome could also be achieved by decreasing the particle size of the powder in suspension. • The amount of suspending agent used in any given formulation depends on the volume of vehicle being thickened. 16 Suspending agents
  • 17. 17 Increase the viscosity of the continuous phase so that the particles remain suspended for sufficiently long time and it becomes easy to measure the accurate dose.  Natural thickening agents are not widely used due to their susceptibility to microbial attack. Hence, the semi-synthetic agents are more widely used. Examples: Natural Thickening agents (Acacia, Tragacanth, sodium alginate) Semi-synthetic Thickening agents (Methyl cellulose [MC], Carboxy methyl cellulose [CMC], Hydroxy propyl methyl cellulose [HPMC], Sodium carboxy methyl cellulose [3.5%] is used in injectable suspensions) Clays (hydrated aluminium silicate, magnesium silicate) Non-ionic substances such as sorbitol, glycerin, sugar or polyethylene glycol [PEG] may be included to adjust the viscosity of the medium.
  • 18. Wetting agents These are the agents that reduce the interfacial tension between the solid particles and the liquid medium by adsorbing at the solid/liquid interface, thus producing a suspension of desired quality. Examples: Alcohol in tragacanth mucilage, Glycerin and glycols in sodium alginate or bentonite dispersions, Polysorbates in oral and parenteral suspensions 18
  • 19. Preservative Presence of suspending agents and medicaments which are liable to bacterial growth make it necessary to incorporate a preservative in a suspension. An effective preservation should be non-toxic, effective against a wide range of micro-organisms, should be stable and compatible with other ingredients of the formulation. Examples:  Benzoic acid, sodium benzoate, methyl paraben and propyl-paraben 19
  • 20. Organoleptic additives Coloring, sweetening and flavoring agents are used in oral suspensions. Similarly, colors and perfumes are incorporated in suspensions meant for external applications but these must be compatible with other ingredients. 20
  • 21. 21 Preparation Of Suspension 1 Simple Dispersion 2 Precipitation of solid from solution
  • 22. 22 Suspensions are prepared by grinding (or) levigating the insoluble materials in the mortar to get a smooth paste with a vehicle (containing the wetting agent if required) All soluble ingredients are dissolved in portion of the vehicle and added to the smooth paste to get slurry. (a semi-liquid thin mixture, of insoluble substance) The slurry is transformed to a graduated cylinder, the mortar is rinsed with successive portion of the vehicle. Add the vehicle containing the suspending agent (or) flocculating agent depending upon the type of final product desired. Make up the dispersion to the final volume 1. Simple Dispersion SUSPENSION
  • 23. 23 1 • Change of pH: if the pH of the medium is changed, the material which was previously soluble at a certain pH, now separates out in fine particles and form suspension 2 • Double Decomposition: Not applicable for pharmaceutical purpose 3 • Change of solvent: Solids show different solubility in different solvents. Chloramphenicol suspension is made by this process. 2. Precipitation of solid from solution
  • 24. Extemporaneous compounding of suspensions (Extemporaneous Suspensions) “the Extemporaneous dispensing of solid dosage form in liquid form” • Such suspensions are prepared just before dispensing to the patient who are unable to swallow the solid dosage form • Mostly in Neonates • Preparation: Crush – Paste – Liquid • Example: Prednisolone suspension, Ketoconazole suspension 24
  • 25. Physical Stability of Pharmaceutical Suspension “Condition in which particles do not aggregate and remain uniformly distributed throughout the dispersion” • This means that if the particles do settle they should be easily resuspended by moderate amount of agitation 25
  • 26. Factors affecting Suspension Stability Stability of suspension depends upon: 26 1. Rate of sedimentation 2. Physical features of Dispersed Phase 3. Features of Dispersion medium 4. Addition of Flocculating Agents 5. Reconstitution of suspension
  • 27. 1. Rate of Sedimentation • Sedimentation: “settling of particles or floccules due to gravity in liquid dosage forms” • Various factors are involved in rate of settling of particles of a suspension which are represented by Stoke‟s Equation. • Stoke‟s equation gives an indication of the factors that can be adjusted to decrease the rate of sedimentation of the formulation. 27
  • 28. 28 Stoke‟s Equation ηՕ • ρ = „rho‟ • η= „eta‟ • Unit of viscosity  Poise= 1 g/cm.sec or pascal sec where 1 Ps= 10P
  • 29. • Large size of particle, higher rate of sedimentation or sedimentation velocity [v ∝ d ] • higher density of particles, higher rate of sedimentation [v ∝ ps] • Higher viscosity of the medium, lower rate of sedimentation [v ∝ 1/ŋ] 29 2
  • 30. 2. Physical features of the Dispersed phase • Properties of suspended particles (suspensoids) and dispersion medium should be considered I. Nature of suspensoid a) Easily Wettable or b) Non-wetting; due to the presence of layer of adsorbed air on the surface, hence forms Clump (Alcohol, Glycerin, Propylene glycol as wetting agent) The use of wetting agent allows to remove this air from the surface and to easy penetration of the vehicle into the pores. The agent flows into the voids between the particles to displace the air and reduce liquid air interfacial tension so that water can penetrate and wet the individual particles. 30
  • 31. 2. Physical features of the Dispersed phase II. Particle size • Probably the most concern thing is the size of particles in suspensions • In good suspensions , the particle diameter is 0.5 to 50 𝛍𝐦 • Reduced particle size produces slow, more uniform rate of settling • Particle size reduction is generally accomplished by dry milling (Milling= grinding with a rotating tool) prior to incorporation of the dispersed phase into the dispersion medium • Micropulvenizers (high speed impact mills) or jet mills (high speed air streams in confined space), spray dryer (solution is sprayed, air dries it) 31
  • 32. Physical features of the Dispersed phase II. Shape of particles • Barrel-shaped or spherical: Symmetrical barrel-shaped particles of calcium carbonate produced more stable suspensions , they do not form cake on standing. • Needle-shaped: Needle shaped are less stable because they form tenacious cake on standing that could not be redistributed 32
  • 33. • Suspensions are physically unstable systems due to particle- particle interaction • This can result in rigid cohesion of particles of suspension which leads to the formation of a cake (agglomeration of particles into larger masses) . • This can ultimately result in suspension instability! 33
  • 34. 34 One simple method of preventing rigid cohesion/ Caking of particles of suspension is “Flocculation”
  • 35. “Intentional formation of a less rigid or loose aggregation* of particles held together by weak particle to particle bonds” (* Floccule) »Benefits: Flocculated particles forming a type of lattice that resists complete settling so are less prone to compaction than deflocculated particles. Additional benefit: loose aggregates easily break up and readily re- dispersed. Flocculation 35
  • 36. Flocculated & Deflocculated Suspensions • Flocculated Suspension “In flocculated suspensions the individual particles are in contact with each other to form loose aggregates and create a network like structure” (Flocules: loose aggregates of particles by weak particle-to-particle/ Van der Waals forces) • Deflocculated Suspension “In non-flocculated or de-flocculated suspensions all individual particles exist as separate entities” 36
  • 37. 37
  • 38. DLVO Theory 38  DLVO theory is a dispersion stabilizing theory which explains that as two particles approach one another their ionic atmospheres begin to overlap and a repulsion force is developed.
  • 39. 39
  • 40. 40
  • 41. Zeta Potential Zeta potential is the potential difference between the ions in the tightly bound layer and the electroneutral region. Zeta potential = potential of the slipping plane Zeta potential governs the degree of repulsion between adjacent, similar charged, solid dispersed particles. 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) 41
  • 42. Sedimentation Evaluation Parameters • Two parameters are used to determine sedimentation in suspensions: 1.Sedimentation volume “F” (Qualitative parameter) 2.Degree of flocculation “B” (Quantitative parameter) • Sedimentation volume or „Height of sediment‟ 42
  • 43. 43 1.
  • 44. 44 2.
  • 45. 45
  • 46. Caking diagram, showing the flocculation of suspension by means of the electrolyte 46 Flocculation zone/ (Sedimentation volume)  this much amount of flocculating agent should be added so that the floccules can be formed, cake formation is prevented.
  • 47. Explanation:  If we disperse particles of bismuth subnitrate (positively charged surface) in water, we find that they possess a high zeta potential. Hence, because of strong forces of repulsion between adjacent particles , the system is de-flocculated and will eventually produce a caked sediment.  Addition of potassium phosphate: as the electrolyte is added, the anion is attracted towards positively charged surface thus decreasing the zeta potential. Hence, now the surface charge is not sufficient to repel the particles and suspension flocculates.  Continuously addition: By continuous addition of electrolyte, the zeta potential falls to zero and increases to negative side as shown in figure.  At a certain zeta potential, maximum flocculation occurs and will persist until zeta potential has become sufficiently negative for de-flocculation to occur once again.  Non caking zone is the zone of balanced zeta potential.  The onset of flocculation coincides with maximum sedimentation volume determined.  F (sedimentation volume) remains constant while flocculation persists and only when the zeta potential becomes sufficiently negative the sedimentation volume starts to fall.  Finally the absence of caking in the suspensions correlates with the max sedimentation volume ,which as stated previously reflects the amount of flocculation.  At less than maximum values of F ,caking become apparent. 47
  • 48. 4. FlocculatingAgents • Controlled flocculation can be achieved by use of flocculating agents. • Flocculating agents are added to enhance particle “re- dispersability” These includes 1. Polymers e.g. bentonite 2. Surfactants: non ionic (mostly used) and ionic surface–active agents 3. Electrolytes: Electrolytes acts as flocculating agents by reducing the electrical barrier between the particles, thus, decrease the zeta potential, this leads to decrease in repulsion potential and makes the particle come together to form loosely arranged structure (floccules). 48
  • 49. 49 • Viscosity of the medium is important which is modified to overcome the problem of rapid sedimentation • Suspending agents like Carboxymethylcellulose, Methylcellulose, Microcrystalline cellulose, Polyvinyl pyrolidone (PVP), xantham gum, bentonite are few of the agents employed to thicken the dispersion medium and help suspend the suspensoid. 4. Features of Dispersion Medium 5. Reconstitution of Suspension • Using the method of reconstitution of suspension right before its use can also keep the suspension stable to some extent. It is important to consider that the suspending agent must be inert, non-toxic, non-interacting with the components of the suspension and should not be in such amount to render the suspension too viscous to agitate or pour.
  • 51. REFERENCES • Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems (9th Edition) • Tutorial Pharmacy by Cooper and Gunn’s 51