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Physical stability of suspensions and
emulsion, role of zeta potential in
stability of coarse dispersions
Presented by:
Name - Amit Sahu
Roll No. โ€“ Y21254005
Class - M. Pharm 2nd Sem.
(Pharmaceutics)
Presented to:
Dr. Dharmendra Jain
Dr. Ashish Jain
Department of Pharmaceutical science
Dr. Harisingh Gour Vishwavidyalaya, Sagar M.P.
Session 2021-22
Physical stability of
suspensions
๏ฑ Physical stability of suspensions
๏‚ง Physical stability is defined as โ€œthe condition in which the
particles remain uniformly distributed throughout the
dispersion system without any signs of sedimentationโ€.
๏‚ง But it is difficult to achieve this condition.
๏‚ง Hance, the definition is restated as โ€“ if the particles settle,
they should be easily redispersedable by a moderate
amount of shaking.
๏ฑ The formulation factors that can be adjusted to
affect the physical stability of the pharmaceutical
suspension are:
1. Sedimentation volume
2. Degree of flocculation
3. Redispersibility
1. Sedimentation volume
5
Sedimentation volume is a ratio of the ultimate volume of sediment
(Vu) to the original volume of sediment (VO) before settling.
Definition:
๐‘ญ =
๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• (๐‘ฝ๐’–)
๐‘ฐ๐’๐’Š๐’•๐’Š๐’‚๐’ ๐‘ฝ๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐‘บ๐’–๐’”๐’‘๐’†๐’๐’”๐’Š๐’๐’ ๐‘ฝ๐’
๐‘ฏ =
๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐‘ฏ๐’Š๐’ˆ๐’‰๐’• ๐’๐’‡ ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• (๐‘ฏ๐’–)
๐‘ฐ๐’๐’Š๐’•๐’Š๐’‚๐’ ๐‘ฏ๐’Š๐’ˆ๐’‰๐’• ๐’๐’‡ ๐’”๐’–๐’”๐’‘๐’†๐’๐’”๐’Š๐’๐’ ๐‘ฏ๐’
๏‚ง F = 1, Vu = Vo, ideal suspension
๏‚ง F = 0, Vu = 0, total instability
๏‚ง Higher the sedimentation volume batter the physical stability.
100 ml
80
60
40
20
100 ml
100 ml
Flocs Hard
cake
Clear
supernatant
Cloudy
supernatant
(a) (b) (c)
60
Sedimentation parameters of
suspensions. Flocculated suspension:
(a) Initial state (F = 1.0);
(b) State of suspension on storage
after some time (F = 0.6), and
(c) Deflocculated suspension.
2. Degree of flocculation
7
It is the ratio of the sedimentation volume of the flocculated
suspension, F, to the sedimentation volume of the deflocculated
suspension, Fa
Definition:
๐œท =
๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’‡๐’๐’๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ฝ๐’–)
๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’…๐’†๐’‡๐’๐’๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ฝ๐œถ)
๐œท =
๐‘บ๐’†๐’…๐’Š๐’Ž๐’†๐’๐’•๐’‚๐’•๐’Š๐’๐’ ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’‡๐’๐’๐’„๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ญ)
๐‘บ๐’†๐’…๐’Š๐’Ž๐’†๐’๐’•๐’‚๐’•๐’Š๐’๐’ ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’…๐’†๐’‡๐’๐’๐’„๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž ๐‘ญ๐œถ
2. Degree of flocculation
๏‚ง In flocculated suspension, formed
flocks. Flocculated suspensions
sediment more rapidly. The volume
of final sediment is thus relatively large
and is easily redispersed by agitation.
๏‚ง In deflocculated suspension, individual
particles are settling, so rate of
sedimentation is slow which prevents
entrapping of liquid medium which
makes it difficult to re-disperse by
agitation. This phenomenon also called
โ€˜'claying".
Flocculated Deflocculated
Clear
supernatant
No much change
in initial
Porous sediment
Little change in
sediment volume
Cake
Short
period
(min)
Medium
period
(hrs
/
day)
Long
period
(weeks
/
yr)
(a)
(b)
(c)
3. Redispersibility
๏‚ง Mechanical shaker device simulating human motion.
Suspension in 100 ml measuring cylinder
๏‚ฏ
Stored to sediment placed in machine, rotated 360ยฐ at 20 RPM
๏‚ฏ
Sediment redispersed time/no. of rotations noted.
๏‚ง Less time/less rotations = disperse ๏‚ฎ stable suspension
๏‚ง More time/ more rotations = disperse ๏‚ฎ unstable suspension.
Physical stability of
emulsion
๏ฑ Physical stability of emulsion
๏‚ง Emulsion stability - Ability to resist changes in its physicochemical
properties with time.
๏‚ง An emulsion is said to stable if it remains as such preparation to its
self life.
๏‚ง Following change might be occurring:
๏ƒ˜ Flocculation
๏ƒ˜ Cracking
๏ƒ˜ Phase inversion
๏ƒ˜ Creaming
๏ƒ˜ Coalescence
Stable emulsion
1. Flocculation
๏‚ง Neighbouring globules come closer to each other and form
colonies in the external phase.
๏‚ง The extent of flocculation of globules depends on:
a) Globule size distribution
b) Charge on the globule surface
c) Viscosity of the external medium
Flocculation
2. Creaming
๏‚ง Creaming is the concentration of globules at the top or bottom
of the emulsion. The floccules move either upward or downward
leading to creaming.
๏‚ง It is a reversible process, i.e., cream can be redispersed easily by
agitation.
๏‚ง Since dreaming process involves the movement of globules in an
emulsion, Stokes' law can be applied.
๐‘ฝ =
๐’…๐Ÿ ๐†๐’” โˆ’ ๐†๐’ ๐’ˆ
๐Ÿ๐Ÿ–๐œผ
๏ถ Factor affecting creaming:
1. Radius of globule.
2. Density of the dispersed phase and dispersion medium.
3. Viscosity.
4. Storage condition.
Upward creaming Downward creaming
O/W W/O
3. Coalescence
๏‚ง A few globules tend to fuse with each other and form bigger
globules.
๏‚ง This step can be recognised by increased globule size and reduced
number of globules.
๏‚ง Coalescence is observed due to:
๏ƒผ Insufficient amount of the emulsifying agent
๏ƒผ Altered partitioning of the emulsifying agent
๏ƒผ Incompatibilities between emulsifying agents
Coalescence
4. Cracking
๏‚ง Cracking means the separation of two layers of disperse and
continuous phase, due to the coalescence of disperse phase.
๏‚ง It is the coalescence of the globules of internal phase and separation of
that phases in to a distinct layer.
๏‚ง This is irreversible.
๏‚ง Reasons for cracking:
๏ƒผ Addition of opposite charged emulsifying agent.
๏ƒผ Decomposition/precipitation of emulsifying agent.
๏ƒผ Addition of common solvent.
๏ƒผ Microorganism.
๏ƒผ Change in temperature. Cracking
Aqueous phase
Oil phase
5. Phase inversion
๏‚ง Phase inversion means change in the type of emulsion i.e. o/w to
w/o or vice versa.
๏‚ง Reasons for phase inversion.
1. Addition of electrolyte.
2. Changing phase volume ratio.
3. Temperature change.
4. Changing the emulsifying agent. Phase inversion
Stable emulsion
Flocculation
Upward
creaming
Downward
creaming
O/W W/O
Coalescence
Cracking
Aqueous phase
Oil phase
Phase inversion
Role of zeta potential
in stability of coarse
dispersions
๏ฑ Electric double layer
-
+
+
+
+
+
+
-
-
-
-
+
+
+
+
+
+
+
-
-
-
- -
-
-
+
+
+
+
+
+
-
-
-
-
-
-
-
-
a
a' bโ€™
b
c' d'
d
c
Solid liquid interphase
Tightly bound
layer
Diffuse layer Bulk liquid
phase
-
-
-
-
-
-
Shear plane Electroneutral region
Nernst potential
Zeta potential
๏ถ Potentials on the electric double layer
๏‚ง Nernst potential:
It is define as potential difference
between actual surface and electro
neutral region.
๏‚ง Zeta potential:
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.
๏ฑ Role of zeta potential in stability of
coarse dispersions
๏‚ง In presence of a high zeta potential the repulsive electrical forces
between two particles exceed the attractive Van der Waals
forces.
๏‚ง The particles dispersed in such a manner are said to be
deflocculated.
๏‚ง Zeta potential can be lowered by the addition of opposite charge
ion that neutralize the surface potential.
๏‚ง At a definite concentration of the added ions the electrical forces of
repulsion are lowered sufficiently and the forces of attraction
predominate.
๏‚ง This may allow the particles to approach each other more closely
and form loose aggregates known as floccules and such a system is
known as a flocculated system.
๏‚ง The flocculated suspension is one in which zeta potential of particle
is -20 to +20 mV.
๏‚ง However the continuous 'addition of the flocculating agent may
reverse the above process if added in enough concentration to cause
the zeta potential to increase sufficiently in the opposite direction.
Caking diagram, showing the flocculation of a bismuth subnitrate
suspension by means of the flocculating agent monobasic potassium
phosphate.
๏‚ง The phenomenon of flocculation and deflocculation depends on
zeta potential carried by particles.
๏ฑ References:
1. Singh Y., Sinko P.J., "Martin's physical pharmacy and
pharmaceutical sciences", 6th edition, New Jersey: Department of
Pharmaceutics Ernest Mario School of Pharmacy Rutgers, The
State University of New Jersey. 2006, page no. 747-771
2. Aulton ME, Taylor K, "Aulton's pharmaceutics: the design and
manufacture of medicines", 5th edition, Elsevier Health Sciences;
2013, Page no.429, 437, 444, 470-473.
3. Subramanyam C.V.S.," Textbook of Physical Pharmaceutics", 2nd
edition, Vallabh prakashan, 2012, page no. 171-173, 376-378,
407-411.
4. Jain N.K., "A textbook of Professional pharmacy", 5th edition,
Vallabh prakshan, 2012 page no. 256,257
5. Slide share โ€“ Coarse dispersion
https://www.slideshare.net/SalmanBaig6/coarse-dispersion
6. Larsson M, Hill A, Duffy J. Suspension stability; why particle size,
zeta potential and rheology are important. Annual transactions of
the Nordic rheology society. 2012 Jan;20(2012):6.
Physical stability of suspensions and emulsions

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Physical stability of suspensions and emulsions

  • 1. Physical stability of suspensions and emulsion, role of zeta potential in stability of coarse dispersions Presented by: Name - Amit Sahu Roll No. โ€“ Y21254005 Class - M. Pharm 2nd Sem. (Pharmaceutics) Presented to: Dr. Dharmendra Jain Dr. Ashish Jain Department of Pharmaceutical science Dr. Harisingh Gour Vishwavidyalaya, Sagar M.P. Session 2021-22
  • 3. ๏ฑ Physical stability of suspensions ๏‚ง Physical stability is defined as โ€œthe condition in which the particles remain uniformly distributed throughout the dispersion system without any signs of sedimentationโ€. ๏‚ง But it is difficult to achieve this condition. ๏‚ง Hance, the definition is restated as โ€“ if the particles settle, they should be easily redispersedable by a moderate amount of shaking.
  • 4. ๏ฑ The formulation factors that can be adjusted to affect the physical stability of the pharmaceutical suspension are: 1. Sedimentation volume 2. Degree of flocculation 3. Redispersibility
  • 5. 1. Sedimentation volume 5 Sedimentation volume is a ratio of the ultimate volume of sediment (Vu) to the original volume of sediment (VO) before settling. Definition: ๐‘ญ = ๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• (๐‘ฝ๐’–) ๐‘ฐ๐’๐’Š๐’•๐’Š๐’‚๐’ ๐‘ฝ๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐‘บ๐’–๐’”๐’‘๐’†๐’๐’”๐’Š๐’๐’ ๐‘ฝ๐’ ๐‘ฏ = ๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐‘ฏ๐’Š๐’ˆ๐’‰๐’• ๐’๐’‡ ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• (๐‘ฏ๐’–) ๐‘ฐ๐’๐’Š๐’•๐’Š๐’‚๐’ ๐‘ฏ๐’Š๐’ˆ๐’‰๐’• ๐’๐’‡ ๐’”๐’–๐’”๐’‘๐’†๐’๐’”๐’Š๐’๐’ ๐‘ฏ๐’
  • 6. ๏‚ง F = 1, Vu = Vo, ideal suspension ๏‚ง F = 0, Vu = 0, total instability ๏‚ง Higher the sedimentation volume batter the physical stability. 100 ml 80 60 40 20 100 ml 100 ml Flocs Hard cake Clear supernatant Cloudy supernatant (a) (b) (c) 60 Sedimentation parameters of suspensions. Flocculated suspension: (a) Initial state (F = 1.0); (b) State of suspension on storage after some time (F = 0.6), and (c) Deflocculated suspension.
  • 7. 2. Degree of flocculation 7 It is the ratio of the sedimentation volume of the flocculated suspension, F, to the sedimentation volume of the deflocculated suspension, Fa Definition: ๐œท = ๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’‡๐’๐’๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ฝ๐’–) ๐‘ผ๐’๐’•๐’Š๐’Ž๐’‚๐’•๐’† ๐’”๐’†๐’…๐’Š๐’Ž๐’†๐’๐’• ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’…๐’†๐’‡๐’๐’๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ฝ๐œถ) ๐œท = ๐‘บ๐’†๐’…๐’Š๐’Ž๐’†๐’๐’•๐’‚๐’•๐’Š๐’๐’ ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’‡๐’๐’๐’„๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž (๐‘ญ) ๐‘บ๐’†๐’…๐’Š๐’Ž๐’†๐’๐’•๐’‚๐’•๐’Š๐’๐’ ๐’—๐’๐’๐’–๐’Ž๐’† ๐’๐’‡ ๐’…๐’†๐’‡๐’๐’๐’„๐’„๐’–๐’๐’‚๐’•๐’†๐’… ๐’”๐’š๐’”๐’•๐’†๐’Ž ๐‘ญ๐œถ 2. Degree of flocculation
  • 8. ๏‚ง In flocculated suspension, formed flocks. Flocculated suspensions sediment more rapidly. The volume of final sediment is thus relatively large and is easily redispersed by agitation. ๏‚ง In deflocculated suspension, individual particles are settling, so rate of sedimentation is slow which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation. This phenomenon also called โ€˜'claying". Flocculated Deflocculated Clear supernatant No much change in initial Porous sediment Little change in sediment volume Cake Short period (min) Medium period (hrs / day) Long period (weeks / yr) (a) (b) (c)
  • 9. 3. Redispersibility ๏‚ง Mechanical shaker device simulating human motion. Suspension in 100 ml measuring cylinder ๏‚ฏ Stored to sediment placed in machine, rotated 360ยฐ at 20 RPM ๏‚ฏ Sediment redispersed time/no. of rotations noted. ๏‚ง Less time/less rotations = disperse ๏‚ฎ stable suspension ๏‚ง More time/ more rotations = disperse ๏‚ฎ unstable suspension.
  • 11. ๏ฑ Physical stability of emulsion ๏‚ง Emulsion stability - Ability to resist changes in its physicochemical properties with time. ๏‚ง An emulsion is said to stable if it remains as such preparation to its self life. ๏‚ง Following change might be occurring: ๏ƒ˜ Flocculation ๏ƒ˜ Cracking ๏ƒ˜ Phase inversion ๏ƒ˜ Creaming ๏ƒ˜ Coalescence Stable emulsion
  • 12. 1. Flocculation ๏‚ง Neighbouring globules come closer to each other and form colonies in the external phase. ๏‚ง The extent of flocculation of globules depends on: a) Globule size distribution b) Charge on the globule surface c) Viscosity of the external medium Flocculation
  • 13. 2. Creaming ๏‚ง Creaming is the concentration of globules at the top or bottom of the emulsion. The floccules move either upward or downward leading to creaming. ๏‚ง It is a reversible process, i.e., cream can be redispersed easily by agitation. ๏‚ง Since dreaming process involves the movement of globules in an emulsion, Stokes' law can be applied. ๐‘ฝ = ๐’…๐Ÿ ๐†๐’” โˆ’ ๐†๐’ ๐’ˆ ๐Ÿ๐Ÿ–๐œผ
  • 14. ๏ถ Factor affecting creaming: 1. Radius of globule. 2. Density of the dispersed phase and dispersion medium. 3. Viscosity. 4. Storage condition. Upward creaming Downward creaming O/W W/O
  • 15. 3. Coalescence ๏‚ง A few globules tend to fuse with each other and form bigger globules. ๏‚ง This step can be recognised by increased globule size and reduced number of globules. ๏‚ง Coalescence is observed due to: ๏ƒผ Insufficient amount of the emulsifying agent ๏ƒผ Altered partitioning of the emulsifying agent ๏ƒผ Incompatibilities between emulsifying agents Coalescence
  • 16. 4. Cracking ๏‚ง Cracking means the separation of two layers of disperse and continuous phase, due to the coalescence of disperse phase. ๏‚ง It is the coalescence of the globules of internal phase and separation of that phases in to a distinct layer. ๏‚ง This is irreversible. ๏‚ง Reasons for cracking: ๏ƒผ Addition of opposite charged emulsifying agent. ๏ƒผ Decomposition/precipitation of emulsifying agent. ๏ƒผ Addition of common solvent. ๏ƒผ Microorganism. ๏ƒผ Change in temperature. Cracking Aqueous phase Oil phase
  • 17. 5. Phase inversion ๏‚ง Phase inversion means change in the type of emulsion i.e. o/w to w/o or vice versa. ๏‚ง Reasons for phase inversion. 1. Addition of electrolyte. 2. Changing phase volume ratio. 3. Temperature change. 4. Changing the emulsifying agent. Phase inversion
  • 19. Role of zeta potential in stability of coarse dispersions
  • 20. ๏ฑ Electric double layer - + + + + + + - - - - + + + + + + + - - - - - - - + + + + + + - - - - - - - - a a' bโ€™ b c' d' d c Solid liquid interphase Tightly bound layer Diffuse layer Bulk liquid phase - - - - - - Shear plane Electroneutral region Nernst potential Zeta potential
  • 21. ๏ถ Potentials on the electric double layer ๏‚ง Nernst potential: It is define as potential difference between actual surface and electro neutral region. ๏‚ง Zeta potential: 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.
  • 22. ๏ฑ Role of zeta potential in stability of coarse dispersions ๏‚ง In presence of a high zeta potential the repulsive electrical forces between two particles exceed the attractive Van der Waals forces. ๏‚ง The particles dispersed in such a manner are said to be deflocculated. ๏‚ง Zeta potential can be lowered by the addition of opposite charge ion that neutralize the surface potential.
  • 23. ๏‚ง At a definite concentration of the added ions the electrical forces of repulsion are lowered sufficiently and the forces of attraction predominate. ๏‚ง This may allow the particles to approach each other more closely and form loose aggregates known as floccules and such a system is known as a flocculated system. ๏‚ง The flocculated suspension is one in which zeta potential of particle is -20 to +20 mV. ๏‚ง However the continuous 'addition of the flocculating agent may reverse the above process if added in enough concentration to cause the zeta potential to increase sufficiently in the opposite direction.
  • 24. Caking diagram, showing the flocculation of a bismuth subnitrate suspension by means of the flocculating agent monobasic potassium phosphate.
  • 25. ๏‚ง The phenomenon of flocculation and deflocculation depends on zeta potential carried by particles.
  • 26. ๏ฑ References: 1. Singh Y., Sinko P.J., "Martin's physical pharmacy and pharmaceutical sciences", 6th edition, New Jersey: Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey. 2006, page no. 747-771 2. Aulton ME, Taylor K, "Aulton's pharmaceutics: the design and manufacture of medicines", 5th edition, Elsevier Health Sciences; 2013, Page no.429, 437, 444, 470-473.
  • 27. 3. Subramanyam C.V.S.," Textbook of Physical Pharmaceutics", 2nd edition, Vallabh prakashan, 2012, page no. 171-173, 376-378, 407-411. 4. Jain N.K., "A textbook of Professional pharmacy", 5th edition, Vallabh prakshan, 2012 page no. 256,257 5. Slide share โ€“ Coarse dispersion https://www.slideshare.net/SalmanBaig6/coarse-dispersion 6. Larsson M, Hill A, Duffy J. Suspension stability; why particle size, zeta potential and rheology are important. Annual transactions of the Nordic rheology society. 2012 Jan;20(2012):6.