1. STABILITY OF COLLOIDS Kausar Ahmad http://staff.iium.edu.my/akausar
Physical Pharmacy 2
4/25/2017
STABILITY OF COLLOIDS
Kausar Ahmad
Physical Pharmacy 2
KBA

2. CONTENTS Lecture 1 1) Non-ionic SAA and Phase Inversion Temperature
2) Stabilisation factors
Electrical stabilisation
Steric stabilisation
Finely divided solids
Liquid crystalline phases
Lecture 2
3) Destabilisation factors
Compression of electrical double layer
Addition of electrolytes
Addition of oppositely charged particles
Addition of anions
4) Effect of viscosity
Physical Pharmacy 2

3. PHASE INVERSION TEMPERATURE
Physical Pharmacy 2
4/25/2017
PHASE INVERSION TEMPERATURE
PIT, or Emulsion Inversion Point (EIP), is a characteristic property of an emulsion (not surfactant molecule in isolation).
At PIT, the hydrophile-lipophile property of non-ionic surfactant just balances.
If temperature >> PIT, emulsion becomes unstable
because the surfactant reaches the cloud point
Physical Pharmacy 2
KBA

4. Physical Pharmacy 2
4/25/2017
CLOUD POINT
Definition - The temperature at which the SAA precipitates.
Common for non-ionic SAA.
As temperature increases, solubility of the POE chain decreases i.e. hydration of the ether linkage is destroyed.
Hydration of POE is most favourable at low temperature.
For the same type of SAA, cloud point depends on length of POE.
Physical Pharmacy 2
KBA

5. PIT FACTOR Cloud point of SAA Salt, acid, alkali, additives
Type of oil
Length of oxyethylene chain
Surfactant system
Salt, acid, alkali, additives
Physical Pharmacy 2

6. PIT FACTOR – CLOUD POINT
Physical Pharmacy 2
4/25/2017
PIT FACTOR – CLOUD POINT
the higher the cloud point in aqueous surfactant solution, the higher the PIT.
This coincides with Bancroft’s rule that the phase in which the emulsifier is more soluble will be the external phase at a definite temperature.
The higher the cloud point, the higher the solubility of the SAA molecule in the aqueous phase.
Thus, only at high temperature will the molecule become insoluble.
Physical Pharmacy 2
KBA

7. Physical Pharmacy 2
4/25/2017
PIT FACTOR – TYPE OF OIL
The more soluble the oil for a non-ionic emulsifier, the lower the PIT.
e.g. at 20oC, POE nonylphenylether (HLB=9.6) dissolves well in benzene, but not in hexadecane or liquid paraffin. The PIT was ca. 110oC compared to only 20oC for benzene with 10% w/w of the emulsifier. -
Physical Pharmacy 2
KBA

8. PIT FACTOR - LENGTH OF OXYETHYLENE CHAIN
Physical Pharmacy 2
4/25/2017
PIT FACTOR - LENGTH OF OXYETHYLENE CHAIN
the longer the chain length, the higher the PIT
e.g. in benzene-in-water emulsions, the PIT increased as the chain length increased
Physical Pharmacy 2
KBA

9. PIT FACTOR - SURFACTANT MIXTURES
Physical Pharmacy 2
4/25/2017
PIT FACTOR - SURFACTANT MIXTURES
when stabilised by a mixture of surfactants, the PIT increased compared to the expected PIT from single surfactant.
e.g. in heptane-in-water emulsion, blending POE nonylphenyl ether having HLB of 15.8 and 7.4 resulted in a higher PIT.
Physical Pharmacy 2
KBA

10. PIT FACTOR - SALTS, ACIDS AND ALKALIS
Physical Pharmacy 2
4/25/2017
PIT FACTOR - SALTS, ACIDS AND ALKALIS
Increase in concentration of salt will decrease PIT of o/w emulsion.
e.g. PIT of cyclohexane-in-water emulsion
NaCl (N)
PIT of o/w (C) 75
1.2 50
in general, addition of salts will destabilise colloidal system
Physical Pharmacy 2
KBA

11. PIT FACTOR - ADDITIVES IN OIL
Physical Pharmacy 2
4/25/2017
PIT FACTOR - ADDITIVES IN OIL
in the presence of fatty acids or alcohols, the PIT of both o/w & w/o emulsions decreases as the concentration of these additives increases, regardless of the chain length of the additives.
e.g. lauric/myristic/palmitic/stearic acids in liquid paraffin-in-water emulsion
Acid (mol/kg)
PIT (C)
100
0.25 30
Physical Pharmacy 2
KBA

12. FORCES OF INTERACTION BETWEEN COLLOIDAL PARTICLES
Physical Pharmacy 2
4/25/2017
FORCES OF INTERACTION BETWEEN COLLOIDAL PARTICLES
Electrostatic forces of repulsion
Van der waals forces of attraction
Born forces – short-range, repulsive force
Steric forces – depends on geometry of molecules adsorbed at particle interface
Solvation forces – due to change in quantities of adsorbed solvent for close particles.
Physical Pharmacy 2
KBA

13. ELECTRICAL THEORIES OF EMULSION STABILITY
Physical Pharmacy 2
4/25/2017
ELECTRICAL THEORIES OF EMULSION STABILITY
Charges can arise from:
Ionisation
Adsorption
The electrical charge on a droplet arises from the adsorbed surfactant at the interface.
Frictional contact
Physical Pharmacy 2
KBA

14. CHARGES ARISING FROM FRICTIONAL CONTACT
Physical Pharmacy 2
4/25/2017
CHARGES ARISING FROM FRICTIONAL CONTACT
For a charge that arises from frictional contact, the empirical rule of Coehn states that: substance having a high dielectric constant (d.c.) is positively charged when in contact with another substance having a lower dielectric constant.
E.g. most o/w emulsions stabilised by non-ionic surfactants are negatively charged – because water has a higher d.c. than oil droplets. At 25oC and 1 atm, the d.c. or relative permittivity for water is 78.5; for benzene ca. 2.5.
Physical Pharmacy 2
KBA

15. ELECTRICAL STABILISATION
Physical Pharmacy 2
4/25/2017
ELECTRICAL STABILISATION
The presence of the charges on the droplets/particle causes mutual repulsion of the charged particles.
This prevents close approach i.e. coalescence, followed by coagulation, which leads to
breaking of an emulsion
Aggregation of solids
Physical Pharmacy 2
KBA

16. STABILISATION OF EMULSIONS BY SOLIDS
Physical Pharmacy 2
4/25/2017
STABILISATION OF EMULSIONS BY SOLIDS
Emulsion Type
0/W
W/O
Petroleum
(Pickering)
Hydrated sulfates of iron, copper, nickel, zinc & aluminum
Kerosene/benzene (Briggs)
ferric hydroxide, arsenic sulfide & silica
Oil phase?
(Briggs)
carbon black & lanolin
Oil phase? (Weston)
Clay
Physical Pharmacy 2
KBA

17. ADSORPTION OF SOLIDS AT INTERFACE
Physical Pharmacy 2
4/25/2017
ADSORPTION OF SOLIDS AT INTERFACE
The ability of solids to concentrate at the boundary is a result of: wo > sw + so
The most stable emulsions are obtained when the contact angle with the solid at the interface is near 90o.
A concentration of solids at the interface represents an interfacial film of considerable strength and stability (compare with liquid crystal!)
Physical Pharmacy 2
KBA

18. STABILISATION BY LIQUID CRYSTALLINE PHASES
Physical Pharmacy 2
4/25/2017
STABILISATION BY LIQUID CRYSTALLINE PHASES
Emulsion stability increases as a result of:
Protection given by the multilayer liquid crystalline phase against coalescence (coalescence due to Van der Waals forces of attraction).
The multilayer adsorbed at the interface prevents thinning of the interfacial films of approaching droplets.
These are achieved due to the high viscosity of the liquid crystalline phases compared to that of the continuous phase.
Physical Pharmacy 2
KBA

19. DESTABILISATION OF COLLOIDS
Physical Pharmacy 2
4/25/2017
DESTABILISATION OF COLLOIDS
Emulsions
Suspensions
Hydrophilic colloid?
Creaming
Phase separation
Demulsification
Ostwald ripening
Heterocoagulation
Flocculation
Coalescence
Caking
Aggregation
Define all the terms above.
Physical Pharmacy 2
KBA

20. Physical Pharmacy 2
4/25/2017
DEMULSIFICATION
By physico-chemical method - Compression of Electrical Double Layer
Add polyelectrolytes, multivalent cations.
Add emulsion/dispersion with particles of opposite charge - HETEROCOAGULATION
Physical Pharmacy 2
KBA

21. EFFECT OF POLYELECTROLYTE
Physical Pharmacy 2
4/25/2017
EFFECT OF POLYELECTROLYTE
Schulze-Hardy Rule states that The valence of the ions having a charge opposite to that of the dispersed particles determines the effectiveness of the electrolytes in coagulating the colloids: suspensions or emulsions.
Thus, presence of divalent or trivalent ions should be avoided.
Preparation should use distilled water, double distilled water, reverse osmosis or ion-exchange water (soft water).
Physical Pharmacy 2
KBA

22. Ostwald Ripening IF oil droplets have some solubility in water.
Physical Pharmacy 2
4/25/2017
Ostwald Ripening
IF oil droplets have some solubility in water.
The extent of Ostwald ripening depends on the difference in the size of the oil droplets.
The larger the particle size distribution, the greater the possibility of Ostwald ripening.
Physical Pharmacy 2
KBA

23. MECHANISM OF OSTWALD RIPENING
Physical Pharmacy 2
4/25/2017
MECHANISM OF OSTWALD RIPENING
The small oil droplets, due to the high SSA, are thermodynamically unstable.
The small oil droplets undergo degradation and thus diffuse into the aqueous phase.
The diffused molecules are then absorbed by the big oil droplets.
The big oil droplets will get bigger and the number of small droplets diminish.
Oil molecule diffused out of small droplet
Oil molecule absorbed by big droplet
Physical Pharmacy 2
KBA

24. OIL DROPLETS IN AQUEOUS MEDIUM
Physical Pharmacy 2
4/25/2017
OIL DROPLETS IN AQUEOUS MEDIUM
POLYDISPERSE SAMPLES
coalescence
Physical Pharmacy 2
KBA

25. DESTABILISATION SCHEME
Physical Pharmacy 2
4/25/2017
DESTABILISATION SCHEME
Rupture of interfacial film
Interfacial film intact
Bridging flocculation
From Florence & Attwood
Physical Pharmacy 2
KBA

26. SEPARATION OF PHASES IN O/W EMULSIONS
Physical Pharmacy 2
4/25/2017
SEPARATION OF PHASES IN O/W EMULSIONS
With 10% surfactant &
Homogenisation for 30 min
Without
homogenisation
Without
surfactant
BREAKING OF EMULSION
Physical Pharmacy 2
KBA

27. DESTABILISATION OF MULTIPLE EMULSION
Physical Pharmacy 2
4/25/2017
DESTABILISATION OF MULTIPLE EMULSION
For w/o/w: Coalescence of internal water droplets.
Coalescence of oil droplets.
Rupture of oil film separating internal and external aqueous phases.
Diffusion of internal water droplets through the oil phase to the external aqueous phase resulting in shrinkage.
One of the main DRIVING FORCES for destabilisation is to reduce the interfacial energy brought about by the small particulates.
Physical Pharmacy 2
KBA

28. DESTABILISATION OF HYDROPHILIC COLLOID
Physical Pharmacy 2
4/25/2017
DESTABILISATION OF HYDROPHILIC COLLOID
Due mainly to depletion of water molecules
when the colloid is contaminated with alcohol
Evaporation of water
Addition of anion
Physical Pharmacy 2
KBA

29. Destabilisation of Hydrophilic Sols by Anions
Physical Pharmacy 2
4/25/2017
Destabilisation of Hydrophilic Sols by Anions
Hofmeister (or lyotropic series): in decreasing order of precipitating power
citrate
tartrate
sulfate
acetate
chloride
nitrate
bromide
iodide
the hydrophilic sols destabilised as a result of the higher affinity for hydration of the ions resulting in the separation of water molecules from the colloidal particles. Thus destabilised.
Exercise: what is the effect of salt on starch solution?
Physical Pharmacy 2
KBA

30. DESTABILISATION OF SUSPENSIONS
Physical Pharmacy 2
4/25/2017
DESTABILISATION OF SUSPENSIONS
as a result of sedimentation
difficult to re-disperse.
Caking
cluster of particles held together in loose open structure (flocs)
Presence of flocs increases the rate of sedimentation.
BUT re-disperse easily.
Flocculation
through dissolution and crystallisation.
Particle growth
Exercise: any particle growth in emulsion?
Physical Pharmacy 2
KBA

31. MINIMISING CREAMING/SEDIMENTATION/CAKING
Physical Pharmacy 2
4/25/2017
MINIMISING CREAMING/SEDIMENTATION/CAKING
Addition of viscosity modifiers
Carboxymethylcellulose (CMC)
Aluminium magnesium silicate
Sodium alginate
Sodium starch
Polymer
Mechanism of their operation:
1) Adsoption onto the surface of particles
2) Increasing the viscosity of medium 3) Bridging
Physical Pharmacy 2
KBA

32. Force acting on particles
Physical Pharmacy 2
4/25/2017
EFFECT OF VISCOSITY
Stoke’s Law
The velocity u of sedimentation of spherical particles of radius r
having a density r in a medium of density ro &
a viscosity ho
& influenced by gravity g is
u = 2r2(r – ro)g / 9ho
Force acting on particles
Gravity
What forces are responsible for the following:
destabilisation of hydrophilic sols by anions
Heterocoagulation
Stabilisation by liquid crystalline phases
Stabilisation by solids
Brownian movement
2-5 μm
Physical Pharmacy 2
KBA

33. VISCOSITY MODIFIER FOR NON-AQUEOUS SUSPENSION
Physical Pharmacy 2
4/25/2017
VISCOSITY MODIFIER FOR NON-AQUEOUS SUSPENSION
E.g. amorphous silica for ointments
Aerosil at 8-10% to give a paste.
The increase in viscosity resulted from hydrogen bonding between the silica particles and oils: peanut oil, isopropyl myristate.
Physical Pharmacy 2
KBA

34. ROLE OF POLYMERS IN THE STABILISATION OF DISPERSIONS
Physical Pharmacy 2
4/25/2017
ROLE OF POLYMERS IN THE STABILISATION OF DISPERSIONS
Addition of polymeric surfactant
adsorption of the polymer onto the particle surface
provides steric stabilization.
increase viscosity of medium
minimise sedimentation
Physical Pharmacy 2
KBA

35. FLOCCULATION
Because of the ability to adsorb, polymers are used as flocculating agent by
promoting inter-particle bridging
BUT, at high concentration of polymers, the polymers will coat the particles (and increase the stability). No floc!
With agitation the flocs are destroyed.
Thus caking may result.
Physical Pharmacy 2

36. FLOCCULATING AGENT E.g. Polyacrylamide (30% hydrolysed)
Physical Pharmacy 2
4/25/2017
FLOCCULATING AGENT
E.g. Polyacrylamide (30% hydrolysed)
an anionic polymer
E.g. Application
only 5 ppm of polyacrylamide is required to flocculate 3% w/w silica sol.
Restabilisation of the colloid occurs when the dosage of polymer exceeds the requirement.
Physical Pharmacy 2
KBA

37. Physical Pharmacy 2
4/25/2017
GEL FORMATION
When particles aggregate to form a continuous network structure which extends throughout the available volume and immobilise the dispersion medium………
The resulting semi-solid system is called a gel.
The rigidity of a gel depends on the number and the strength of the inter-particle links in this continuous structure.
Peptisation is a process in which dispersion is achieved with little or no agitation, by changing the composition of the dispersion medium.
This may be achieved by:
addition of polyvalent co-ions (e.g. polyphosphate ions to a negatively charged coagulated dispersion)
addition of surfactants
dilution of the dispersion medium
dialysis
In each case, VR is modified so as to create a potential energy maximum to act as a barrier against recoagulation.
The sensitisation of a hydrophobic colloid occurs when a hydrophilic or hydrophobic colloid of opposite charge is added.
Due to compression of the electrical double layer.
Physical Pharmacy 2
KBA

38. Physical Pharmacy 2
4/25/2017
REFERENCES
PC Hiemenz & Raj Rajagopalan, Principles of Colloid and Surface Chemistry, Marcel Dekker, New York (1997)
HA Lieberman, MM Rieger & GS Banker, Pharmaceutical Dosage Forms: Disperse Systems Volume 1, Marcel Dekker, New York (1996)
F Nielloud & G Marti-Mestres, Pharmaceutical Emulsions and Suspensions, Marcel Dekker, New York (2000)
J Kreuter (ed.), Colloidal Drug Delivery Systems, Marcel Dekker, New York (1994)
Physical Pharmacy 2
KBA