2. ❑ Dispersed systems are systems which consist of:
1. Particulate matter (dispersed phase)
➢ It is the component present in small proportion
and is just like a solute in a solution
2. Dispersion medium (continuous phase)
➢ A component present in excess and is just like a
solvent in a solution
Dispersed
phase
Dispersion
medium
2
Dispersed system
26-Jan-23 a4kgetmes
3. 26-Jan-23 3
Dispersed system
➢Based on particle size: dispersed systems are classified as
Molecular dispersion, Colloidal dispersion and Coarse dispersion
< 1 nm 1 - 500 nm > 500 nm
Property
Particle size
Diffusion
Visibility
Filtration
Settling
Molecular Colloidal Course
Particles diffuse
rapidly
Very slow diffusion Don’t diffuse
Invisible under
electromicroscop
e
Visible under
electromicroscope
Visible under
lightmicroscope
Pass SPM and
filter paper
Pass filter paper
but not SPM
Not pass filter
paper or SPM
Do not settle Settle under
centrifugation
Settle under
gravity
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4. 26-Jan-23 4
Types of Colloidal Systems
➢ Based on the interaction b/n the two phases colloids are
classified as:
✓Lyophilic colloids: contains particles which interacts with the
dispersion medium to an appreciable extent
✓Example Acacia or gelation in water
✓Lyophobic colloids: composed of materials having poor/no
interaction with the dispersion medium
✓Generally inorganic particles such as gold and silver
✓Association colloids: composed of materials having
amphiphilic nature which could result in to micelles
✓The concentration ---> CMC
✓The no of monomers ---> Aggregation number
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5. 26-Jan-23 5
Lyophilic
(solvent-loving)
Lyophobic
(solvent-hating).
Association (amphophilic).
Dispersed
phase
Large organic molecules
lying within colloidal size
Inorganic particles such as
gold and silver
Micelles of small organic
molecules (size < colloidal size)
Solvation Solvated Little solvation Depends on the medium
(Hydrophilic/lipophilic)
Preparatio
n
Spontaneous (dissolving
in solvent
Needs special procedure Spontaneous (conc. > CMC)
Viscosity Increases with conc. & at
certain conc. Form a gel.
Not greatly increased due
to no solvation
Increased with conc./micell no.
Effect of
electrolyte
s
Stable but de-solvation &
salting out at high conc.
Unstable due to surface
charges neutralization
CMC is reduced and salting out
occur at high salt conc.
Types of Colloidal Systems
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6. 26-Jan-23 6
Optical Properties of Colloids
a4kgetmes
Faraday-Tyndall effect and Light scattering
➢ When a strong beam of light is passed through colloidal
dispersions, the light rays form a visible cone (Tyndall cone)
resulting from the light scattered by colloidal particles.
✓ This is called the Faraday-Tyndall effect
➢ This cone formation (Tyndall cone) and Turbidity define the
optical appearance of colloidal dispersions.
7. 7
Optical Properties of Colloids
➢ Turbidity is a fractional decrease in the intensity of an incident
light due to scattering as it passes through a medium.
➢ This light scattering provides information on the particle size,
shape and molecular weight of colloids.
✓ For instance, molecular weight is directly related to turbidity
26-Jan-23
Where τ (cm-1) is turbidity = Is/I
C (g/cm3) is concentration
M (g/mole) is average molecular weight
B is an interaction constant
H is constant for particular system
Hc/τ = 1/M + 2Bc
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➢ A plot of HC/τ Vs C provides a
straight line with
✓ A slope of 2B and
✓ Y-intercept of 1/M
8. 8
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kinetic Properties of Colloids
26-Jan-23
➢Brownian motion
✓ It is a random/erratic and continuous movement of colloidal
particles within a dispersion medium.
✓ It results from uneven distribution of collision on the
particles from the molecules of the dispersion medium
✓ This motion is affected by different factors including
✓ Temperature: generally enhances Brownian motion
✓ Particles size: smaller particles move faster
✓ Viscosity: high viscosity limits Brownian motion.
9. 26-Jan-23 9
✓ As a consequence of Brownian motion in a stable colloidal
system:
• The gravitational force (sedimentation) is counteracted
• Colloidal particles diffuse from high to low concentration
kinetic Properties of Colloids
➢Diffusion
✓ It is a spontaneous movement of particles from a higher to
a lower concentration until a system is uniform throughout.
✓ Fick’s first law states “The amount of substance diffusing in
time (dm/dt) across an area (A) is directly proportional to a
change of conc. with distance traveled (dc/dx)”
a4kgetmes
10. 26-Jan-23 10
kinetic Properties of Colloids
➢Osmotic pressure
✓ It is the driving force in osmosis as is the concentration
gradient for diffusion.
✓ The osmotic pressure of a dilute colloidal dispersion can be
described by van’t Hoff’s equation
a4kgetmes
11. 26-Jan-23 11
Sedimentation
Stoke’s law: For spherical particles
V: rate of sedimentation
r: radius of the particle
d: particle diameter
ρ: density of the particle
ρo: density of the medium
η: viscosity of the medium
g: acceleration due to gravity
Limitations of the Stock’s law
➢ It was derived for dilute dispersions and does not take into
consideration inter-particulate interactions.
➢ Thus, it may not be exactly applicable to a concentrated
dispersion system.
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12. 26-Jan-23 12
Electric Properties of Colloids
➢Electrical properties of colloids are those properties which
depend on, or are affected by, the presence of a charge on the
surface of a particle.
✓Physical stability of colloids
➢ Why particles in a liquid acquire charge?
✓Ion dissolution.
✓Ionization.
✓Ion adsorption (Selective adsorption of a particular ionic
species present in the solution).
a4kgetmes
13. Ion dissolution
❑ Ionic substances can acquire a surface charge by unequal
dissolution of the oppositely charged ions. For instance
➢ Silver iodide particle in a solution with
• Excess iodide, the AgI particles acquire a negative charge
• Excess silver, the AgI particles acquire a positive charge
– Hence, the conc. of Ag and I determine the electric
potential
➢ Similarly, Aluminum hydroxide particles in a solution with
excess hydroxide will acquire a negative charge & vice versa.
26-Jan-23 13
Electric Properties of Colloids
(AgI)m
I- I
-
I
-
a4kgetmes
14. Ionization
❑ Surface charge of colloidal particle is controlled by the
ionization of surface groupings. For instance
➢ Polystyrene latex has carboxylic acid group at the surface,
ionize to give negatively charged particles.
➢ Acidic drugs as ibuprofen & nalidixic acid acquire surface
negative charged.
➢ Amino acids & proteins have carboxyl & amino groups whose
ionization depend on the pH as follow;
NH2-R-COO-
Negatively charged NH3
+-R-COO-
Zwitter ion (neutral)
NH3+-R-COOH
low pH (Acidic medium)
NH2 -R- COOH
14
Electric Properties of Colloids
@ high (Alkaline)pH
@ Isoelectric point
@ low (Acidic) pH
26-Jan-23 a4kgetmes
15. 26-Jan-23 15
Electric Double Layer (EDL)
➢As shown in previous slides, colloidal particles carry electrical
charge on their surface (–ve /+ve) => potential determining ions
➢Consequently, the surface charge attracts counter ions, together
with the dispersion medium, on to the surface of the particles.
✓ Depending on the magnitude and sign (+ve or –ve) of the charge
➢These adsorption proceeds until the surface charge is neutralized
and results in a layer called EDL
➢An EDL is an electrically neutral layer surrounding a dispersed
phase, including adsorbed ions and a film the dispersion medium.
➢An EDL is a phenomenon that plays a fundamental role in the
electrostatic stabilization of colloids.
Electric Properties of Colloids
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16. 26-Jan-23 16
Electric Properties of Colloids
➢For instance let’s consider an EDL that results from the dispersion
of AgI particles in an aqueous solution of NaI
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17. 26-Jan-23 17
Electric Properties of Colloids
➢ Nernst potential (E) is the potential at the solid surface aa’, due
to the potential determining ions
➢ The difference in potential between the actual surface and the
electroneutral region of the solution
➢ Zeta potential (ζ) is the potential
located at the shear plane bb’ due to
the contribution of the counter ions.
➢ The potential difference between the
surface of tightly bound layer (shear
plane) and the electroneutral region of
the solution
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18. 26-Jan-23 18
Electric Properties of Colloids
➢ Zeta potential (ζ) can be determined from one of the
electrokinetic property of colloidal particles- Electrophoresis
➢ Electrophoresis is the mov’t of a charged particle through a liquid
under the influence of applied electric current (potential)
✓ The rate of particle migration is a function of the charge on
the particle (zeta potential)
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19. 26-Jan-23 19
Electric Properties of Colloids
➢ The magnitude of zeta potential can be determined by
• V= velocity of migration,
• ɛ = dielectric constant,
➢ If the dispersion medium used is water and at 20 oC, the above
equation becomes:
• ɳ = viscosity,
• E = potential gradient (volt/cm)
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21. 26-Jan-23 21
➢ Important terms to be considered in physical stability of colloids
• Aggregation, Coagulation and Flocculation
Physical stability of colloidal systems
➢ Aggregation
✓ is a general term signifying the
collection of particles into groups.
➢ Flocculation
✓ Is when aggregated particles have
an open structure with a small
distance remain b/n them.
➢ Coagulation
✓ Is when aggregated particles are
closely packed making it difficult
to redisperse them.
a4kgetmes
23. ➢ The physical stability of colloidal dispersions depends on the
balance of involved forces:
✓ Electrical forces of repulsion between dispersed phase
particles (the zeta potential)
✓ Forces of attraction between dispersed phase particles
(including van der Waals force of attraction)
✓ Forces of attraction between the dispersed phase and the
dispersion medium
26-Jan-23 23
Physical stability of colloidal systems
a4kgetmes
24. ❑ Stabilization serves to prevent colloids from aggregation.
N.B:
➢ Hydrophilic and association colloids are thermodynamically
stable
➢ Lyophobic or hydrophobic colloids are thermodynamically
unstable
❑ Two main mechanisms for lyophobic colloid stabilization:
➢ 1-Steric stabilization
• surrounding particles with polymer molecules attached to
its surface forming a coating, which creates a repulsive
force and separates the particle from another particle.
➢ 2-electrostatic stabilization
• providing the particles with electric charge
26-Jan-23 24
Physical stability of colloidal systems
a4kgetmes
25. ❑ Derjaguin and Landau and, independently, Verwey and
Overbeek, in the 1940s produced a quantitative approach to the
stability of hydrophobic colloids.
➢ DLVO theory of colloid stability
❑ They assumed that the only interactive forces
involved are:
➢ van der Waals attraction (VA) and
➢ electrical repulsion, (VR)
❑ And these parameters are additive.
➢ Thus the total potential energy of interaction
VT =VA + VR
26-Jan-23 25
DLVO theory of colloid stability
a4kgetmes
26. ➢ The DLVO theory explains the tendency of dispersed particles to
agglomerate or remain discrete by combining the van der Waals
attraction curve with the electrostatic repulsion curve to form the
net interaction.
26-Jan-23 26
DLVO theory of colloid stability
a4kgetmes
27. • The curve shows that:
• Attraction predominates at small
distances, hence the very deep
primary minimum.
• The attraction at large interparticle
distances that produces the
secondary minimum arises
• Because the fall-off in repulsive
energy with distance is more rapid
than that of attractive energy.
• At small and at large distances the
van der Waals energy is greater than
the repulsion
• At intermediate distances double-
layer repulsion may predominate,
giving a primary maximum in the
curve, particles stay dispersed
26-Jan-23 27
DLVO theory of colloid stability
a4kgetmes
28. ❑ If the maximum is too small, two interacting particles may
reach the primary minimum
➢ Will form aggregation
❑ When the maximum in VT total is sufficiently high, the two
particles do not reach the stage of being in close contact.
➢ Stable colloid will be formed
26-Jan-23 28
DLVO theory of colloid stability
a4kgetmes
29. ❑ Therapeutic purpose
➢ Colloidal system are used as therapeutic agents in different
areas.
Eg. Silver colloid → germicidal
Copper colloid → anticancer
Mercury colloid → Antisyphilis
❑ Stability, solubility
➢ Colloidal coatings to solid dosage forms are used to protect
drugs that are susceptible to atmospheric moisture or
degradation under the acid condition of the stomach.
➢ Association colloids are used to increase solubility &
stability of certain compounds in aqueous & oily
pharmaceutical preparations.
26-Jan-23 29
Application of colloids
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30. ❑ Absorption
➢ As colloidal dimensions are small enough, they have a huge
surface area.
• Hence, the drug constituted in colloidal form is released in
large amount.
e.g. sulphur colloid gives a large quantity of sulphur
❑ Targeted Drug Delivery
Eg. Liposomes are of colloidal dimensions and are preferentially
taken up by the liver and spleen.
➢ Hence, principle of colloids is also used in targeted drug
delivery system
26-Jan-23 30
Application of colloids
a4kgetmes
32. ❑ A pharmaceutical suspension is a dispersion in which internal
phase (API)is dispersed uniformly throughout the external phase.
❑ The internal phase consisting of insoluble solid particles having a
size range of (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.
Pharmaceutical suspensions
26-Jan-23 32
a4kgetmes
33. Classifications of suspensions
❑ Based on route of administration
➢ Oral suspension eg: Paracetamol suspension, antacids
➢ Externally applied suspension eg : Calamine lotion
➢ Parenteral suspension eg: Penicillin G Benzathine, Insulin Zinc
Suspension
❑ Based on proportion of solid particles
➢ Dilute suspension (2 to10%w/v solid): cortisone acetate
➢ Concentrated suspension (50%w/v solid): zinc oxide
suspension
Suspensions…
26-Jan-23 33
a4kgetmes
34. ❑ Based on Electrokinetic Nature of solid particles
➢ Flocculated suspension
➢ Deflocculated suspension
❑ Based on size of solid particles
➢ Coarse suspensions: Suspensions with suspended particle
sizes of 1 to 100 µm
➢ Colloidal suspensions: Suspensions with suspended particle
sizes of 1 nm to 1 µm.
➢ Nano suspensions: Suspensions with suspended particle sizes
of < 1 nm
Suspensions…
26-Jan-23 34
a4kgetmes
35. ❑ Based on the ease of suspendability the solid particle:
➢ Diffusible suspensions
• Contain light powders (insoluble, or only very slightly
soluble) but after shaking disperse evenly throughout the
vehicle for long enough
❑ Examples of diffusible powders commonly incorporated into
pharmaceutical suspensions
* Light Kaolin BP (insoluble in water)
* Light Magnesium Carbonate BP (very slightly soluble)
* Magnesium Trisilicate BP (insoluble )
Suspensions…
26-Jan-23 35
a4kgetmes
36. ❑ In-diffusible suspensions
➢ contain heavy powders that are insoluble in the vehicle
and on shaking do not disperse evenly throughout the
vehicle long enough
Examples:
* Aspirin BP
* Calamine BP
* Chalk BP
* Zinc Oxide BP
Suspensions…
26-Jan-23 36
a4kgetmes
37. Advantages:
❑ Suspension can improve chemical stability of certain drug.
• Powder for reconstitution
• Drugs prone to hydrolysis: Tetracycline/oil
❑ Drug in suspension exhibits higher rate of bioavailability than
other dosage forms.
• Solution > Suspension > Capsule > Compressed Tablet > Coated tablet
❑ To mask the unpleasant odour/bitter taste of drugs
Eg: paracetamol suspension (more palatable)
❑ Suspension can be used for topical applications
Eg: calamine lotion Bp
❑ Suspension can be formulated for parentral application
E.g. Penicillin G Benzathine
Advantages and Disadvantages
26-Jan-23 37
a4kgetmes
38. Disadvantage
❑ 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 a stable and acceptable suspension
❑ Uniform and accurate dose can not be achieved unless
suspension are packed in unit dosage form.
Advantages and Disadvantages…
26-Jan-23 38
a4kgetmes
39. ❑ Resuspend easily upon shaking
❑ Physically, chemically and microbiologically stable during its
shelf life
❑ Uniform dispersion
❑ Sterile (parenteral, ocular)
❑ Gets into syringe (parenteral, ocular)
❑ Pleasing odor and color and Palatable
❑ Easy to pour yet not watery and no grittiness
❑ Temperature insensitive
Properties of an Ideal Suspension
26-Jan-23 39
a4kgetmes
40. ❑ Some FACTORS TO BE CONSIDERED during formulation of
suspensions are:
• PARTICLE SIZE CONTROL
• WETTING
• SEDIMENTATION
• ZETA POTENTIAL
Theoretical consideration of suspensions
26-Jan-23 40
a4kgetmes
41. 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 μm
– impart a gritty texture to the product
– cause irritation if injected or instilled to the eye
• particles > 25 μm may block the needle
❑ Too fine particles will
• easily form hard cake at the bottom of the container.
Theoretic consideration of suspensions…
26-Jan-23 41
a4kgetmes
42. WETTING OF THE PARTICLES
❑ Hydrophilic materials (such as talc and Mg2CO3) are easily wetted
by the dispersion medium commonly water
❑ Conversely, hydrophobic materials (such as sulphur and charcoal)
are not easily wetted b/c a layer of adsorbed air on their 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 removal of this air from the
surface and to easy penetration of the vehicle into the pores.
❑ However, hydrophobic materials are easily wetted by non-polar
dispertion liquids.
Theoretic consideration of suspensions…
26-Jan-23 42
a4kgetmes
43. SEDIMENTATION
❑ Sedimentation means settling of particle or floccules occur
under gravitational force in liquid dosage form.
❑ Velocity of sedimentation is expressed by Stoke’s equation
v =
d2 (p1-p2) g
18
v =
d2 (p1-p2) g
18
where v is the terminal velocity in cm/sec.
d is the diameter of the particle in cm,
p1 and p2 are the densities of the dispersed phase and dispersion
medium, respectively.
g is the acceleration due to gravity, and is the viscosity of the
dispersion medium in poise
Theoretic consideration of suspensions…
26-Jan-23 43
a4kgetmes
44. ❑ According to Stoke’s Law rate of sedimentation of particles
in a suspension may be reduced by:
➢ decreasing particle size
➢ increasing viscosity
➢ Narrowing density difference of dispersed and
dispersion phase
Theoretic consideration of suspensions…
26-Jan-23 44
a4kgetmes
45. ZETA POTENTIAL
❑ Zeta potential is a measure of repulsive forces.
❑ 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
❑ The flocculated suspension is one in which zeta potential of
particle is -20 to +20 mV.
❑ Thus the phenomenon of flocculation and de flocculation
depends on zeta potential carried by particles.
Theoretic consideration of suspensions…
26-Jan-23 45
a4kgetmes
46. Flocculated Suspensions
❑ In flocculated suspensions, zeta potential is lower than critical
values where attractive forces are greater than repulsive forces
❑ This lower zeta potential leads to the formation of loose
aggregates of particles (flocs) => flocculation
❑ Zeta potential can be lowered by addition of a small amount of
electrolyte or nonionic surfactants to deflocculated suspensions
❑ The formed flocs will cause increase in sedimentation rate due to
increase in size of sedimenting particles.
➢ Hence, flocculated suspensions sediment more rapidly.
❑ However, this formation of flocs and rapid sedimentation allows
the entrapment of dispersion medium
Deflocculation and Flocculation…
26-Jan-23 46
a4kgetmes
47. Deflocculated suspensions
❑ In deflocculated suspensions, the zeta potential is higher than
critical value where repulsive forces supersede attractive ones.
❑ Consequently, particles remains suspended for a long period of
time, and only a small portion of the suspended particles are
found in the sediment due to the force of gravitation.
❑ In deflocculated suspension, individual particles are settling with
a slow rate of sedimentation
❑ This prevents the entrapment of the dispersion medium between
settling particles making it difficult to re-disperse by agitation.
❑ This phenomenon is called ‘caking’ or ‘claying’.
Deflocculation and Flocculation
26-Jan-23 47
a4kgetmes
48. Flocculated Deflocculated
1. Particles forms loose aggregates and
form a network like structure
2. Rate of sedimentation is high
3. Sediment is rapidly formed
4. Sediment is loosely packed and
doesn’t form a hard cake
5. Sediment is easy to redisperse
6. Suspension is not pleasing in
appearance
7. The floccules stick to the sides of the
bottle
1. Particles exist as separate entities
2. Rate of sedimentation is slow
3. Sediment is slowly formed
4. Sediment is very closely packed
and a hard cake is formed
5. Sediment is difficult to redisperse
6. Suspension is pleasing in
appearance
7. They don’t stick to the sides of the
bottle
Deflocculation and Flocculation…
26-Jan-23 48
a4kgetmes
49. ❑ The formulation of a suspension depends on whether the
suspension is flocculated or deflocculated.
❑ Three approaches are commonly involved
– Use of structured vehicle
– Use of controlled flocculation
– Combination of both of the methods
Formation of suspensions
26-Jan-23 49
a4kgetmes
50. Flow chart of formulation of suspension
Finely divided Particles
Addition of
structured vehicle
Addition of wetting agent and dispersion medium
Deflocculated suspension
in structured vehicle as a
final product
Flocculated
suspension
Flocculated
suspension as a final
product
Uniform dispersion of deflocculated particles
Addition of
flocculating agent
Addition of
flocculating agent
Addition of
structured vehicle
Flocculated suspension in
structured vehicle as a final
product
26-Jan-23 50
a4kgetmes
51. STRUCTURED VEHICLE
❑ Structured vehicles are aqueous solutions of natural gums and
synthetic (modified) polymers.
❑ Structured vehicles are also known as thickening or suspending
agents.
❑ The main aim of these agents is to increase the viscosity of the
suspension, or specifically the dispersion medium.
❑ These structured vehicles entrap the particles and reduce their
sedimentation.
❑ E.g. methyl cellulose, sodium carboxy methyl cellulose, acacia,
gelatin and tragacanth.
Formation of suspensions…
26-Jan-23 51
a4kgetmes
52. CONTROLLED FLOCCULATION
❑ Controlled flocculation of particles is obtained by adding
flocculating agents, which are:
– Electrolytes
– Surfactants
– Polymers
FLOCCULATION IN STRUCTURED VEHICLES
❑ Sometimes suspending agents can be added to flocculated
suspension to retard sedimentation
❑ Examples of these agents are: Carboxymethylcellulose (CMC)
Formation of suspensions…
26-Jan-23 52
a4kgetmes
53. ❑ Suspending agent: form colloidal dispersion with Water and
increase the viscosity of the continuous phase.
➢ Preferred suspending agents are those that give thixotropy to the
media such as Xanthan gum, Carageenan, Na CMC.
❑ Wetting agent: increase wettability: Alcohol, glycerin, and propylene
glycol, polysorbate 80
❑ Buffers: control the pH: acetate, phosphate citrate, carbonate
❑ Osmotic agents: added to produce osmotic pressure comparable to
biological fluids: NaCl, manitol, dextros
Formation ingredients used in suspensions
26-Jan-23 53
a4kgetmes
55. ❑ Small scale preparation of suspensions:
Step 1: The insoluble materials are ground (levigated) in a mortar
with the vehicle and wetting agent in to a smooth paste.
Step 2: All soluble ingredients are then dissolved in same portion of
the vehicle and added to the smooth paste to get a slurry.
Step 3: The slurry is transferred to a graduated cylinder, the mortar
is rinsed with successive portion of the vehicle.
Step 4: Add a vehicle containing the suspending agent/ flocculating
agent and then make up the dispersion to the final volume
Preparation of suspensions
26-Jan-23 55
a4kgetmes
56. Sedimentation method :
❑ Two parameters are studied for determination of sedimentation.
1. Sedimentation volume
2. Degree of flocculation
Evaluation of suspensions
26-Jan-23 56
a4kgetmes
57. 1. Sedimentation volume
❑ The ratio of the equilibrium volume of the sediment (Vu) to the
total volume of the suspension (Vo)
F = Vu / Vo = Hu/Ho
❑ F has values ranging from less than one to greater than one.
➢ When Vu < Vo F < 1
➢ When Vu = Vo F =1, flocculation equilibruim, shows no clear
supernatant on standing
➢ When Vu > Vo, F > 1, the network of flocs formed is so loose
(fluffy) that their volume is greater than the original volume.
❑ However, sedimentation volume lacks a meaningful reference
point it gives only qualitative account of flocculation
Evaluation of suspensions…
26-Jan-23 57
a4kgetmes
59. 2. Degree of flocculation (β)
❑ In a suspension that is completely deflocculated, the ultimate
volume of sediment will be relatively smaller than that of
flocculated suspension.
F∞=V∞ /Vo, F=Vu/Vo
❑ Degree of flocculation 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]/[V ∞ /Vo]= Vu/V∞
❑ The minimum value of ß is 1,when flocculated suspension
sedimentation volume is equal to the sedimentation volume of
deflocculated suspension.
Evaluation of suspensions…
26-Jan-23 59
a4kgetmes
60. 60
Example 1:
Determine the sedimentation volume of a 2.5% w/v suspension of
paracetamol in water. The initial volume of the suspension was 100 mL
while the final volume of the sediment was found to be 44 mL. If the
degree of flocculation is 1.5, what is the deflocculated sedimentation
volume?
Example 2:
A 200 mL of suspension of a drug in water was made and the final volume
of the sediment was found to be 60 mL. Calculate the sedimentation
volume and deflocculated sedimentation volume if the degree of
flocculation is found to be 1.3.
Eg.3. Calculate the sedimentation volume and the deflocculated
sedimentation volume of 5%w/v suspension of magnesium carbonate in
water if initial volume is 100ml, final volume is 30ml and degree of
flocculation is 1.3
26-Jan-23 a4kgetmes
61. ❑ Pharmaceutical suspensions for oral use are generally packed in
wide mouth container having adequate space above the liquid to
ensure proper mixing.
❑ Generally glass and various grades of plastics are used in
packaging of suspension
❑ Parenteral suspensions are packed in either glass ampoules or
vials.
Packaging of suspensions
26-Jan-23 61
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62. Labeling:
❑ 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.
Storage:
❑ Stored at controlled temperature from 20-25 0C
❑ Suspensions should be stored in cool place but should not be
kept in a refrigerator
Storage requirements & labeling
26-Jan-23 62
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64. ❑ An emulsion is a system consisting of two immiscible liquid
phases, one of which is dispersed throughout the other in the
form of fine droplets.
❑ Heterogeneous systems of one liquid dispersed throughout
another in the form of droplets
Compositions
❑ Internal/Discontinuous/Dispersed phase
➢ The phase that is present as fine droplets
❑ External/Continuous phase
➢ The phase in which the droplets are dispersed
❑ Emulsifying agent
➢ Used to stabilize the emulsion
26-Jan-23 64
Emulsions…
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65. ❑ Pharmaceutical emulsions usually consist of water and an oil.
➢ depending upon whether the continuous phase is aqueous or
oily, two main types can exist:
A) Oil-in-water (o/w)
B) Water-in-oil (w/o)
65
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Emulsions…
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66. ❑ For oral administration, o/w emulsions are used while for
external use, both o/w and w/o systems can be employed.
❑ Semisolid emulsions are termed as creams
➢ O/w creams are less greasy and are easily washable after
application.
➢ W/o creams are greasy, with high apparent viscosity
• have an occlusive effect and are therefore preferred as
moisturizing lotions.
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Emulsions…
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67. ❑ O/W emulsions are administered by all the major parenteral
routes
❑ W/o emulsions are generally reserved for IM or SC
administration where sustained release is required
➢ Drug action is prolonged in such oily emulsions because the
drug has to diffuse from the aqueous dispersed phase
through the oil-continuous environment to reach the tissue
fluids
➢ Besides, w/o emulsion is generally of high viscosity: difficult
to inject
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Emulsions…
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68. Multiple emulsions
❑ Are emulsions whose disperse phase contains droplets of another
phase
➢ An oil droplet enclosing a water droplet may be suspended in
water to form a water-in-oil-in water emulsion (w/o/w)
• Use: as delayed-action drug delivery systems
• lower the viscosity of w/o emulsion
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Emulsions…
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69. ❑ When two immiscible liquids are mixed, shaken together or
mechanically agitated both phases tend to form droplets of
various sizes.
❑ The surface free energy of the system, which is dependent on
both total surface area and interfacial tension is raised by the
increase in surface area produced during dispersion,
➢ Thus the system becomes thermodynamically unstable, which
results in coalescence of these droplets
❑ If agitation ceases, coalescence will continue until complete
phase separation, the state of minimum free energy, is reached
26-Jan-23 69
Emulsions formation
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70. ❑ To prevent coalescence of emulsion, emulsifying agents are
included
❑ Emulsifiers can be grouped into three groups:
1) surface active agents
2) natural (macromolecular) polymers and
3) finely divided solids.
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Emulsions formation…
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71. ✓ Surfactants adsorption at the oil-water interface form
monomolecular films
• Presence of the surfactant monolayer at the surface of
the droplet reduces the possibility of collisions
– helps to maintain the particles in a dispersed state
❑ The choice of surfactant depends on its solubility to the
phases
❑ In general, the phase in which the emulsifier is most soluble
becomes the continuous phase
• Hydrophilic surfactants→ o/w emulsions (HLB:9-12)
• Lipophilic surfactants promote w/o emulsions (HLB:3-6)
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Emulsions formation…
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72. ✓ Natural (macromolecular) polymers
▪ Multimolecular Adsorption and Film Formation
➢ Hydrated lyophilic colloids can be regarded as surface
active, but they differ from synthetic surfactant
❖ They do not cause an appreciable lowering of
interfacial tension
❖ They form a multi-rather than a monomolecular film
at the interface
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Emulsions formation…
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73. ✓ Solid-Particle adsorption
➢ Finely powdered solid particles are wetted to some
degree by both oil and water can act as emulsifying agents
➢ Powders that are wetted preferentially by water form o/w
whereas those more easily wetted by oil form w/o
emulsions
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Emulsions formation…
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74. 26-Jan-23 74
Table. Emulsifying agents derived from natural products and finely divided solids
Emulsions formation…
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75. Other ingredients used in emulsions
❑ Antioxidants: butylated hydroxy toulene (BHT) and butylated
hydroxyanisole (BHA)
❑ Humectants: propylene glycol, glycerol, and sorbitol are often
added to dermatological preparations
❑ Preservatives: benzoic acid, parahydroxybenzoic acid esters,
phenoxyethanol, Chloroform Water
➢ W/o emulsions are less susceptible to attack than o/w
emulsions because the aqueous continuous external phase
can produce ideal conditions for the growth of bacteria,
moulds and fungi.
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Emulsions formation…
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76. ❑ Bacteria can degrade nonionic and anionic emulsifying agents,
Glycerin, Vegetable gums (as thickeners);
➢ Resulting in: Phase separation, Gas and odor formation,
discoloration , Changes in rheological properties
❑ Two phase system: adequate concentration of preservative should be
available in water phase as bacteria mainly grow in aqueous phase
• Therefore, Preservative should
– strongly partitioned in favor of water
– be in its un-ionized form to penetrate bacterial membrane
– not be bound to other components of the emulsion
76
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Preservation of Emulsions
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77. ❑ Emulsion may be prepared in different methods
❑ In small scale
➢ a mortar and pestle, a mechanical blender, a homogenizer.
❑ In large scale,
➢ Colloid mills, high-pressure homogenizers, microfluidizers,
ultrasonic homogenizers may be used to prepare an
emulsion.
❑ In small scale, there are three main methods of Emulsion
Preparation
1. Continental or dry gum method.
2. English or wet gum method.
3. Bottle method.
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Methods of Emulsion preparation
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78. ❑ Also referred to as the 4-2-1 method
• Oil -4 parts by volume
• Aqueous phase -2 parts by volume
• Gum -1 part by weight
❑ The preparation of an emulsion has two main components:
➢ Preparation of a concentrate called the ‘primary emulsion’.
➢ Dilution of the concentrate.
❑ The proportions are important when making the primary
emulsion, to prevent the emulsion breaking down on dilution
or storage.
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Dry gum method
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79. ❑ Example 1. What quantities would be required to produce 200
mL of 30% v/v Cod liver oil emulsion?
➢ 60mL of Cod Liver Oil BP is required, therefore 4 parts
60mL.
➢ Two parts would be equivalent to 30 ml aqueous phase.
➢ 1 part would be equivalent to 15 g of gum
26-Jan-23 79
Dry gum method
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80. 1. The acacia or O/W emulsifier is triturated with the oil in a
dry mortar, until uniformly mixed.
2. The two parts of water are added all at once.
➢ Then the mixture is triturated immediately, rapidly and
continuously until the primary emulsion is formed.
• (The end point of the preparation could be noticed
when a creamy white and crackling sound or ‘clicking’
sound is observed).
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Dry gum method, steps
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81. 3. Other liquid ingredients that are soluble in the external phase
may then be added.
4. Solid substances such as active ingredient, preservatives,
colorants, and flavoring agent usually dissolved in water then
added to an emulsion.
5. Any substance which might reduce the physical stability of the
emulsion, such as alcohol (which may precipitate the gum)
should be added as near to the end of the process as possible
to avoid breaking the emulsion
6. Finally QS with water to final volume
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Dry gum method, steps
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82. ❑ The same proportion of water, gum and oil is used but the
process is different
❑ More difficult to use, but produces a more stable product
❑ Produces O/W emulsion
Steps:
1. Triturating of acacia with water in a mortar.
2. The oil is added slowly in portions, triturating continuously.
3. The mixture is triturated for several minutes to form the
primary emulsion.
4. Additional water can be added after the primary emulsion is
prepared
5. Other substances may be added.
6. Finally QS with water to final volume
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Wet gum method
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83. ❑ Another variant of the Continental Method
❑ It is used for volatile oils or oleaginous substances of low
viscosity.
1. The powder acacia is placed in a dry bottle.
2. Two parts of oil then added.
3. The bottle is then capped and shaken.
4. Water is then added immediately in portions.
5. Shaken until primary emulsion is formed
6. Additional water can be added after the primary emulsion is
prepared
5. The other ingredients are added.
6. Finally QS with water to final volume
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Bottle method
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84. ❑ Dilution test
❑ Dye solubility test
❑ Conductivity test
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Tests for identification Emulsion type
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85. ❑ A stable emulsion may be defined as a system in which
the
• Globules retain their initial character
• Remain uniformly distributed throughout the continuous
phase.
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Physical stability of emulsion
• Different instability problems
• Reversible: such as creaming and flocculation
• irreversible: such as coalescence and Ostwald ripening
a4kgetmes
87. CREAMING and SEDIMENTATION
❑ The disperse phase, according to its density relative to that of the
continuous phase, rises to the top or sinks to the bottom of the
emulsion, forming a layer of more concentrated emulsion.
➢ If the dispersed phase is less dense than the continuous phase
(o/w emulsion), the velocity of the sedimentation becomes
negative, an upward creaming
➢ If the dispersed phase is more dense than the continuous
phase (w/o emulsion), the velocity of the sedimentation
becomes positive, downward creaming
87
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Physical stability…
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88. 88
➢ The rate of creaming can be increased
✓ If the density difference is greater
✓ By increasing the force of gravity through centrifugation
✓ By increasing the diameter of the globule
❑ Creaming is undesirable from a pharmaceutical point of view:
➢ Creamed emulsion is inelegant in appearance,
➢ Possibility of inaccurate dosage,
➢ Increases the likelihood of coalescence as the globules are
close together in the cream.
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Physical stability…
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89. ❑ Rate of sedimentation will be decreased by:
➢ reduction in the globule size (eg by homogenizing the
emulsion)
➢ increasing viscosity of continuous phase (eg. by the use of
thickening agents such as tragacanth or methyl cellulose)
➢ decrease in the density difference between the two phases
89
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Physical stability…
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90. FLOCCULATION
❑ A weak reversible association between emulsion globules
separated by thin films of continuous phase.
➢ The individual droplets retain their separate identities, but
each floccule or cluster of droplets behaves physically as a
single unit.
➢ The association arises from the interaction of attractive and
repulsive forces between droplets
90
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Physical stability…
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91. COALESCENCE
❑ Where dispersed phase droplets merge to form larger droplets
❑ Factors:
• Relative magnitude of forces between droplets
• Disruption of interface
• Dehydration, freezing
❑ Strategies to reduce coalescence
➢ Adding thickening or gelling agent
➢ Increase thickness of interface
➢ Increase repulsion or reduce Attraction
91
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Physical stability…
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92. CRACKING or BREAKING
❑ Separation of an emulsion into its constituent phases
➢ the disperse phase coalesces and forms a separate layer.
➢ Re-dispersion cannot be achieved by shaking and the preparation
is no longer an emulsion.
❑ Cracking can occur if the oil turns rancid during storage
➢ Addition of a chemical that is incompatible with the
emulsifying agent, thus destroying its emulsifying ability.
Eg. Surface active agents of opposite ionic charge, (e.g. the
addition of cetrimide (cationic) to an emulsion stabilized
with sodium oleate (anionic))
92
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Physical stability…
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93. ❑ Bacterial growth: protein materials and non-ionic surface-active
agents are excellent media for bacterial growth;
❑ Temperature change:
➢ rise in temperature: protein emulsifying agents may be
denatured and the solubility characteristics of non-ionic
emulsifying agents change
➢ Freezing: ice formed disrupt the interfacial film around the
droplets
93
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Physical stability…
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94. PHASE INVERSION
❑ This refers to the process whereby there will be an exchange
between the disperse phase and the dispersion medium.
• For example, an O/W emulsion may with time or change of
conditions invert to a W/O emulsion
Causes
➢ Coalescence: results in the formation of progressively larger
droplet which leads to phase separation
➢ Factors that affect the HLB of the system,
Eg. , temperature and/or electrolyte concentration
94
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Physical stability…
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95. ❑ Volume fraction of the disperse phase
➢ For stability of an emulsion, the optimum range of
concentration of dispersed phase is 30–60% of the total volume.
➢ If the disperse phase exceeds this the stability of the emulsion is
questionable.
➢ As the concentration of the disperse phase approaches a
theoretical maximum of 74% of the total volume, phase
inversion is more likely to occur.
❑ Addition of electrolyte
➢ Addition of CaCl2 in to o/w emulsion formed by sodium stearate
can be inverted to w/o emulsion
95
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Physical stability…
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