Kulliyyah of Pharmacy, IIUM Physical Pharmacy 2 4/15/2017 Stability of Colloids Kausar Ahmad Kulliyyah of Pharmacy, IIUM http://staff.iiu.edu.my/akausar Physical Pharmacy 2 KBA

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

Phase Inversion Temperature Physical Pharmacy 2 4/15/2017 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

Physical Pharmacy 2 4/15/2017 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

PIT Factor – Cloud point Physical Pharmacy 2 4/15/2017 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

Physical Pharmacy 2 4/15/2017 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

PIT Factor - Length of oxyethylene chain Physical Pharmacy 2 4/15/2017 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

PIT Factor - Surfactant mixtures Physical Pharmacy 2 4/15/2017 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

PIT Factor - Salts, acids and alkalis Physical Pharmacy 2 4/15/2017 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

PIT Factor - Additives in oil Physical Pharmacy 2 4/15/2017 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

FORCES OF INTERACTION between colloidal particles Physical Pharmacy 2 4/15/2017 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

Electrical theories of emulsion stability Physical Pharmacy 2 4/15/2017 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

Charges arising from frictional contact Physical Pharmacy 2 4/15/2017 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

Electrical stabilisation Physical Pharmacy 2 4/15/2017 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

Stabilisation of emulsions by SOLIDS Physical Pharmacy 2 4/15/2017 Stabilisation of emulsions by SOLIDS The first observations on emulsions stabilised by solids were made by Pickering. Basic sulfates of iron, copper, nickel, zinc and aluminum in moist conditions act as efficient dispersing agents for the formation of petroleum o/w emulsion The DRY calcium carbonate can also promote emulsification but emulsion not stable. Physical Pharmacy 2 KBA

Emulsion formation with solids Physical Pharmacy 2 4/15/2017 Emulsion formation with solids Briggs observed formation of o/w emulsion with kerosene/benzene and ferric hydroxide, arsenic sulfide and silica w/o emulsions were produced with carbon black and lanolin Weston produced o/w and w/o emulsions with clay. Moist precipitates are better emulsifiers Highly gelatinous or highly dispersed precipitates are more efficient than granular. Aluminum hydroxide precipitates improved on ageing (why?)  Exercise: predict HLB of silica, carbon black, lanolin Physical Pharmacy 2 KBA

Adsorption of solids at interface Physical Pharmacy 2 4/15/2017 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

Stabilisation by Liquid Crystalline Phases Physical Pharmacy 2 4/15/2017 Stabilisation by Liquid Crystalline Phases Emulsion stability increases as a result of: Protection given by the multilayer against coalescence due to Van der Waals forces of attraction. Prevent thinning of the 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

Destabilisation of Colloids Physical Pharmacy 2 4/15/2017 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

Demulsification By physico-chemical method Compression of double layer Physical Pharmacy 2 4/15/2017 Demulsification By physico-chemical method Compression of double layer Add polyelectrolytes, multivalent cations. add emulsion/dispersion with particles of opposite charge - HETEROCOAGULATION Physical Pharmacy 2 KBA

Effect of polyelectrolyte Physical Pharmacy 2 4/15/2017 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

Ostwald Ripening If oil droplets have some solubility in water. Physical Pharmacy 2 4/15/2017 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

Mechanism of Ostwald Ripening Physical Pharmacy 2 4/15/2017 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

Oil droplets in aqueous medium Physical Pharmacy 2 4/15/2017 Oil droplets in aqueous medium spherical Polydisperse sample coalescence Non-spherical Physical Pharmacy 2 KBA

Destabilisation scheme Physical Pharmacy 2 4/15/2017 Destabilisation scheme Rupture of interfacial film Interfacial film intact Bridging flocculation From Florence & Attwood Physical Pharmacy 2 KBA

Separation of phases in o/w emulsions Physical Pharmacy 2 4/15/2017 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

Destabilisation of Multiple Emulsion Physical Pharmacy 2 4/15/2017 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

Destabilisation of hydrophilic colloid Physical Pharmacy 2 4/15/2017 Destabilisation of hydrophilic colloid Due to mainly Depletion of water molecules when the colloid is contaminated with alcohol Evaporation of water Addition of anion Physical Pharmacy 2 KBA

Destabilisation of Hydrophilic Sols by Anions Physical Pharmacy 2 4/15/2017 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

Destabilisation of suspensions Physical Pharmacy 2 4/15/2017 Destabilisation of suspensions Caking as a result of sedimentation difficult to re-disperse. Flocculation cluster of particles held together in loose open structure (flocs) Presence of flocs increases the rate of sedimentation. BUT re-disperse easily. Particle growth through dissolution and crystallisation. Exercise: any particle growth in emulsion? Physical Pharmacy 2 KBA

Minimising Creaming/Sedimentation/Caking Physical Pharmacy 2 Minimising Creaming/Sedimentation/Caking 4/15/2017 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

Effect of viscosity Stoke’s Law Forces acting on particles Physical Pharmacy 2 4/15/2017 Effect of viscosity Stoke’s Law Forces acting on particles 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 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

Viscosity modifier for non-aqueous suspension Physical Pharmacy 2 4/15/2017 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

Role of polymers in the stabilisation of dispersions Physical Pharmacy 2 4/15/2017 Role of polymers in the stabilisation of dispersions Addition of polymeric surfactant adsorption of the polymer onto the particle surface provides steric stabilization. may increase viscosity of medium minimise sedimentation Physical Pharmacy 2 KBA

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

Flocculating agent Polyacrylamide (30% hydrolysed) Application Physical Pharmacy 2 4/15/2017 Flocculating agent Polyacrylamide (30% hydrolysed) an anionic polymer which can induce flocculation in numerous system such as silica sols and kaolinite at very low concentrations. 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

Definition - Gel Formation Physical Pharmacy 2 4/15/2017 Definition - Gel Formation When the 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

Physical Pharmacy 2 4/15/2017 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) http://www.chemistry.nmsu.edu/studntres/chem435/Lab14/double_layer.html Physical Pharmacy 2 KBA