EMULSIONS INTRODUCTION

Emulsion is a thermodynamically unstable system consisting of at least two immiscible phase, one of which is dispersed in the other liquid phase, the system being stabilized by an emulsifying agent. One phase is the disperse phase which is distributed throughout the other continuous phase or dispersion medium. Emulsions can be liquids or semi-solids. The latter are referred to as creams. The particle or globule size is 0.1-10μ. When the globule size is < 5μ they are called fine emulsions but can have emulsions <10nm which are called microemulsions.

STABILITY AND FORMULATION OF SUSPENSIONS

In the preparation of suspensions, particle size is reduced. There is an increase in the specific area, which cause an increase in surface free energy. These parameters are expressed in the following relationship:

            ΔF = γΔA                    Where ΔF  = increase in free energy

                                                            γ = interfacial tension

                                                            ΔA = increase in surface area.

With large F, the particles are highly energetic and tend to regroup so as to reduce the total area. Thus suspensions like other dispersed systems are thermodynamically unstable. The particles tend to flocculate, i.e. form light, fluffy conglomerates, held together by weak Van der Waal’s forces of attraction. But they may adhere firmly to form aggregates, which grow and fuse to form a solid. The suspension is then said to have undergone caking or forming a cake.

The smaller the ΔF the more the thermodynamic stability. ΔF can be reduced by reducing γ (e.g. using wetting agents or surfactants) or by reducing ΔA. γ cannot be reduced to zero, thus particles although deflocculated, settle slowly, forming a hard cake eventually, which is difficult to re-disperse. ΔA is reduced by deliberately formulating loose aggregates or flocs which although settle rapidly, they do not pack tightly at the bottom due to porous nature. They form a loose mass that can be redistributed with minimum agitation.

Question:

A hypothetical suspension contain 10³ spherical particles of diameter d = 10^-3 cm. (a)Assuming that the interfacial tension between the solid and the liquid is γ_SL = 100 dyne/cm, compute the total surface free energy, ΔF. (b) The solid particles are divided  to obtain 100 particles from each initial particle. Compute the increase in total surface area and the total surface free energy ΔF’ for the divided particles. (HINT: Compute the volume of a particle to get its new radius and surface area. Assume that the density of the particle is unity.

FORMULATION OF SUSPENSIONS:

Formulation of suspensions calls for a compromise between:

1.      Keeping the particles in a suspension as long as possible and having a cake on standing.

2.      Deliberately forming agglomerates which although settle rapidly are easy to re-disperse.

RECALL

                    i.            Forces acting between two articles in a disperse system (resultant of attractive and repulsive forces, DLVO theory).

                  ii.            Particles are charged (How do particles in a dispersed system acquire a charge? How can we ascertain that particles in a disperse system are charged?)

                iii.            Factors affecting zeta potential and their effect on stability of dispersed systems.

                 iv.            What are the secondary minimum and its importance in the formulation of suspensions?

Deflocculation:

Zeta potential is reflective of the potential at the surface of a particle (Nernst Potential). When ξ potential is high, repulsive forces are higher than attractive forces. Particles are deflocculated. Slowly sedimentation occurs, forming a closely packed arrangement, smaller particles filling the voids of larger ones. Lowermost articles are pressed together, the energy barrier is overcome and particles touch. The particles remain attracted to each other and form a hard cake.

Flocculation.

a. ΔF = 0.314 erg; b) ΔF’ = 1.45 erg

Addition of a preferentially adsorbed ion, having a charge opposite to that of the particle, neutralizes the surface potential and progressively lowers the ξ potential, thus lowering repulsive forces. When attractive forces still dominate, the particles approach each other more closely forming aggregation called flocs. The system is flocculated. The added substance is called flocculating agent. Addition of more flocculating agent can increase the zeta potential to opposite direction leading to deflocculation again.

Settling:

This one aspect of instability. In order to control it let us see the factors involved:

SEDIMENTATION RATE:

1. Stoke’s law:

ν = 2r2 (δ – δ₀ )g    Where g = acceleration due to gravity

            9 η₀

ν =The velocity of sedimentation,

r = radius of a spherical particles

δ =  density of particles

 δ₀ = density of medium

 η_{0 =} viscosity

 

To reduce the sedimentation rate, we can reduce the particle size, r. (particles shall be deflocculated) or increase viscosity (but should not impede flow).

Question: A coarse powder with a true density of 2.44 g/cm³ and a mean diameter  d of 100 µm was dispersed in a 2% carboxymethylcelulose dispersion having a density ρ₀ of 1.010 g/cm³. The viscosity of the medium at low shear rate was 27 poises. Using Stoke’s law, calculate the average velocity of sedimentation of the powder in cm/sec.

2. Brownian motion:

Particles lower than 2μ show Brownian movement and the rate of sedimentation is lower than would be expected from Stoke’s law and may even remain suspended for prolonged periods of time due to this phenomenon. But this effect is eliminated when high viscosity liquids are used e.g. glycerin.

3. Effect of flocculation

In deflocculated systems, large particles settle faster than smaller particles. Very small particles remain suspended longer such that no distinct boundary between the supernatant and the sediment. In flocculated systems, flocs tend to fall together, producing a distinct boundary between sediment and the supernatant liquid. The supernatant is clear, showing that very fine particles have been incorporated in flocs. Here we use the term subsidence rather than sedimentation.

SEDIMENTATION PARAMETERS

Sedimentation volume, F

F = ratio of equilibrium or final volume of the sediment, V_u to the original volume of the suspension, V_o.

                              F =  V_u                                F ranges from 0-1

                                                         V_o

F is only a qualitative representation, but no meaningful reference. A more useful parameter is the degree of flocculation. The ideal suspension has F=1. This means there is no sedimentation or caking and the suspension is esthetically appealing.

Degree of Flocculation, β

This is more meaningful. For a completely deflocculated suspension,

      F∞ = V∞

               V_o

V∞ is very small.

Degree of flocculation d relates the sedimentation volume of the flocculated suspension, F to the sedimentation volume of the deflocculated suspension, F∞.

β  = F

      F∞

That is β = V_u/ V_{o                  =}              V_u

                  V∞/ V_o                                V∞

That is if β = 5, the volume of sediment in flocculated system is 5X that in a deflocculated system. If β =  7, it is more preferable.

FORMULATION OF SUSPENSIONS

In the formulation of a stable suspension,

1.      We need a structured vehicle to maintain deflocculated particles in suspension.

2.      Principles of flocculation are applied to produce flocs which although settle rapidly are easily resuspended.

Structured vehicles are plastic or pseudoplastic, frequently associated with thixotropy. They act by entrapping the deflocculated particles so that settling is discouraged. Though sedimentation occurs to some degree due to shear thinning property of the vehicles, a uniform dispersion is reformed easily on application of shear. (remember flocculated systems cake on standing).  The principle then is to formulate flocculated particles in a structured vehicle of hydrophilic colloid and hence principles of controlled flocculation are applied.

How is controlled flocculation achieved?

1.      The first step is to reduce the particle size. Use mortar and pestle, agitators, homogenizer, colloid mills etc

2.      Particles must be wetted. Some particles are not easily wettable and will not remain in vehicle long enough to ensure uniformity of dosage. Here wetting agents are needed as well as thickening agents to increase viscosity and delay sedimentation. Such materials are called indiffusible solids, e.g. sulfur, charcoal magnesium stearate.  Their angle of contact is approximately 90º. They are hydrophobic. Surfactants reduce surface tension and therefore lower angle of contact. Also glycerin and other hydroscopic materials can be used to improve wetting properties. Some powders however are easily wetted (eg light kaolin, Ca carbonate, Zinc Oxide, Talc). They show small or no angle of contact and sink. They easily mix with water and on shaking diffuse evenly through liquid. These are diffusible or dispersible substances.

3.      Controlled flocculation

Electrolytes, surfactants and polymers are used to control flocculation to avoid caking. They are known as flocculating agents.

Electrolytes:

They lower the electrical barrier between particles (decrease the zeta potential), and form a bridge between particles to link them in a loosely arranged structure. For example, bismuth subnitrate (positively charged particles) is deflocculated (due to repulsive forces between particles). Addition of potassium acid phosphate (KH2PO4), which is negatively charged, decreases zeta potential due to adsorption of KH2PO4 on bismuth subnitrate. Progressively zeta potential is reduced to zero and then reverts to negative. At a certain zeta potential maximum flocculation occurs. At this point, there is maximum degree of flocculation. Flocculation exists until zeta potential is sufficiently negative to cause deflocculation again and subsequent caking.Similarly, Aluminium chloride (positively charged) added to sulfamerazine (negatively charged) would bring about the same effect.

Surfactants:

Both ionic and non-ionic surfactants can bring about flocculation. Since they also act as wetting agents their concentration is crucial.

Polymers

The long chain high molecular weight compounds have active groups along their chain. Part of the chain is adsorbed on particle surface and the other part projects in the dispersion medium. By bridging between the latter portions flocs are formed. Hydrophilic polymers act as protective colloids and hence reduce the caking tendency. They also exhibit pseudoplastic flow (eg gelatin). Sodium sulfathiazole is negatively charged in aqueous solution. If it is precipitated from acid solution in presence of gelatin it is positive, free flowing and does not cake. This is because gelatin is positive and is coated on sulfathiazole. The coated particles are flocculated and do not cake. The strong negative charge has been replaced by small positive charge.

Flocculation in structured vehicle.

Suspending agents.

Controlled flocculation alone results in unsightly preparations. Thus suspending agents are used to retard sedimentation of flocs which would make the preparation unsightly. They try to make the sedimentation volume F close to 1. For example, carboxymethyl cellulose (CMC) carbapol 934, veegum, tragacanth, bentonite or combination. But addition of suspending agents may lead to problems of incompatibilities. For example, if a positively charged particles are dispersed and flocculated  by a correct negatively charged electrolyte, there is no problem when the hydrocolloid is used to improve physical stability. This is because most hydrocolloids are negatively charged. But if the particles were negatively charged and cationic electrolyte is used for stabilization, addition of hydrocolloid will cause incompatibility. Therefore to overcome such a problem, we use protective colloid to change the sign from negative (ve-) to positive (ve+). For example non-toxic fatty acid amine is used so that on addition of hydrocolloid (anionic) there is no problem.

Types of thickening agents.

Polysaccharides

·         Natural: Acacia, tragacanth, starch, sodium alginate

·         Semisynthetic: methylcellulose, hydroxymethyl cellulose, sodium carboxy methyl Cellulose

Inorganic agents: Clay, bentonite, Aluminium magnesium silicate,

Aluminium hydroxide.

Synthetics:  Carbomer (carboxy nvinyl polymer), colloidal silicon dioxide

Rheological considerations

Viscosity studies are very important in suspensions. Viscosity affects

§  Settling of particles

§  Flow properties on shaking, pouring and spreading qualities of lotions and Flow properties during  manufacturing.

§  Passage of suspensions in syringe needle.

An ideal suspending agent should have high viscosity at negligible shear (during storage when the only shear is due to settling of particles) and low viscosity at high shear rate 9that it free flowing during agitation, pouring and spreading. Hence it should be pseudoplastic and preferably thixotropic. Sometimes suspending agents are combined to give better properties eg bentonite and CMC are combined and give average properties: bentonite has marked hysteresis loop and CMC is thixopropic.

Preparation of suspensions

Small scale.

The insoluble matter is ground or levigated t a smooth paste with a vehicle containing the dispersion stabilizer. The remaining liquid phase in which any soluble drugs may be dissolved is gradually added. Volatile ingredients are also dissolved in the vehicle. The slurry is transferred to a tared container; the mortar is rinsed with successive portions of the vehicle. Finally the dispersion is brought to final volume.

Large scale:

Mills are used ( ball mill, colloid mill, pebble mill). Dough mixer or pony mixer may be needed as well. The colloid mill has a cone shaped high velocity rotor centered in a stator at a small adjustable clearance. The materials are fed through a hopper to the rotor by gravity, and here they are sheared between the rotor and the stator., and forced out below the stator, where it may be recycled or drawn off. The efficiency of the mill depends on the clearance of discs, velocity of rotor and viscosity of suspension.

SUSPENSIONS: Introduction, Desirable Qualities, Importance and Applications.

Pharmaceutical suspension = a coarse dispersion in which finely divided solid particles are dispersed is a liquid medium.

IMPORTANCE:

Ø  Suspensions supply insoluble and often distasteful substances in a form which is pleasant to the taste.

Ø  Suspensions provide suitable forms of application of dermatological materials to the skin and mucous membranes

Ø  Suspensions provide parenteral administration of insoluble drugs.

DESIRABLE QUALITIES OF A SUSPENSION

·         Is composed of small uniformly sized particles.

·         Suspended materials must not settle rapidly.

·         Should the particles settle, they must be easily redistributed. They should not form a hard cake.

·         Should not be too viscous to pour freely from the orifice of the container or to flow through a syringe needle.

·         For external lotions, suspensions must spread easily on application, but not too mobile as to run off the surface. The lotion must dry quickly to give a protective film.

·         Suspensions should have acceptable odour and taste.

o   Should be resistant to microbial attack (may need a preservative)

o   Must have optimum physical, chemical and pharmacological activities.

PHARMACEUTICAL APPLICATION OF SUSPENSIONS

·         Suspensions provide liquid preparations of insoluble drugs to patients who find it difficult to swallow tablets and capsules.

·         To avoid hydrolysis, some drugs are synthesized as insoluble salts and suspended in a suitable medium. Compare oxytetracycline hydrochloride (insoluble) and oxytetracycline calcium (soluble).

·         To avoid prolonged contact with liquid, powders are prepared and suspensions are made just prior to use. E.g. ampicillin syrup (expires 7-14 days after reconstitution.

·         Provide alternative for aqueous sensitive drugs, which are suspended in non-aqueous vehicles.

·         Formulation in finely divided particles offer a high surface area suitable for some drug action e.g. kaolin suspension, Mg trisilicate and MgCO₃ suspensions.

·         Fine powders may provide protective action against loss of volatile materials for inhalation e.g. Menthol and Eucalyptus are adsorbed on light Mg carbonate for prolonged release (compared to solutions).

·         Suspensions may mask an otherwise obnoxious taste eg. Compare Paracetamol elixir (bitter) and suspension (no taste, can be sweetened)., or chloramphenicol palmitate is more acceptable in children. Taste is less noticeable in insoluble form.

·         Topical application may be suitable e.g. calamine lotion leaves a protective action after the vehicle has evaporated.

·         Parenteral suspensions have controlled release characteristics (variation in particle size increase duration of action, or suspension may be formulated in oily phase).

·         Vaccines are often formulated as suspensions and provide prolonged antigenic stimulus leading to increased antibody titre.

·         Some X-ray contrast media are formulated as suspension (insoluble materials in aqueous vehicle).

APPLICATION OF COLLOIDS

The therapeutic properties of some medicinal products are increased when they are formulated in colloidal state. For example

1.      Colloidol calome (Hg nitrate , gelatin, NaCl) has higher antiseptic activity than in the coarse powder.

2.      Colloidal Silver chloride (AgCl), Silver Iodide (AgI), and Silver (Ag) proteins are germicidal which do not cause irritation as their ionic Ag salts.

3.      Adsorption of toxins from GIT by kaolin and the rate of neutralization of excess acidity in the stomach by Aluminium hydroxide is higher if the compounds are in colloidal form.

4.      Blood plasma substitutes are colloidal dispersions in which the particle size is big to allow retention in blood vessels for adequate time (eg dextran inj BP, polyvinyl pyrolidone (PVP).

5.      Natural and synthetic polymers are in colloidal range. Starch, cellulose are pharmaceutical adjuncts; synthetic polymers are used as coatings to tablets for protection against moisture and acid degradation in stomach.

6.      Colloidal dispersions containing radioactive isotopes are used for diagnostic and therapeutic purposes in nuclear medicine. Technetium 99^m sulphur colloid is used in liver, spleen and bone scanning. Radioactive colloids that accumulate in tumors, lesions or emboli indicating their location and size may be used as diagnostics. The radiation emitted is made visible by scanning devices. Radiocolloids are useful in treatment of cancer because they accumulate in target organs.

PREPARATION OF COLLOIDS

Lyophobic dispersions

The most common medium for lyophobic dispersion is water. Insoluble organic and inorganic compounds usually with a low degree of hydration are dispersed in aqueous medium and are intrinsically unstable. The particles tend to coalesce or aggregate to reduce the surface area and hence surface energy. Thus special means must be utilized to stabilize these systems –preventing the otherwise spontaneous coalescence or coagulation of the disperse phase after it has been finely dispersed. There are two methods of preparing lyophobic sols, namely Condensation methods (aggregation of small molecules or ions until particles of colloidal dimensions are obtained) and dispersion methods (reducing coarse particles to colloidal dimensions through comminution or peptization).

Condensation Method:

This method involves aggregation of small molecules or ions until particles of colloidal dimensions result.

To illustrate this method, the preparation of sulphur hydrosol is exemplified. Whereas sulphur is insoluble in water, it soluble in alcohol. Alcohol and water are miscible. Sulphur is dissolved in alcohol, and the solution is mixed with water to produce a bluish-white colloidal dispersion. The dispersion must be stabilized to avoid precipitation or agglomeration. The same method can be used to prepare hydrosol of stearic acid, mastic acid and other polymers.

Suphur vapor may also be stremed in water to produce a colloidal dispersion. This is a less common method.

Condensation may also be produced chemically. For example bubbling hydrogen sulphide (H₂S) gas into a solution of sulphur dioxide (SO₂) :

2H2S   +  SO₂    ===>                       3S   +   H₂O

or mixing solutions of sodium thiosulphate and sulfuric acid:

===>H₂SO4 + 3NaS₂O₃                             4S +NaSO₄ + H₂O

Aluminium hydrxide sol is produced by hydrolysis of Aluminium chloride.

            AlCl₃  +  3 H₂O                          ===> Al(OH)₃ + 3HCl                                

** See preparation of White lotion (precipitated ZnS and S)

Dispersion method:

The methods involve reducing coarse particles to colloidal dimensions through comminution or peptization.

Mechanical disintegration: 

Using equipment such as micronizers, colloid mills, homogenizers, or even simple mortar and pestle, solids and liquids are sheared or attrited into fine size for dispersion. Ultrasonic generators produce waves that break soft materials e.g. sulphur, talcum and graphite into very small particles or droplets. Thus method is used to produce very fine emulsions for I.V. use.

The dispersion must be stabilized to avoid re-crystallization, coagulation or calescence.

Peptization:

This involves breaking up aggregates into smaller particles. It is synonymous to defflocculation. It can be brought by removing flocculating agent (eg electrolyte) or addition of a deffloculating agents or peptizing agents (eg surfactants, ions or water soluble polymers). Eg activated charcoal produces a grey dispersion, Addition of 0.1% Na laurylsulphate or octoxynol disintegrates the particles into fine ones, results in fine deep black dispersion.  

Purification of colloidal dispersions

Hydrosols may contain low molecular weight water-soluble impurities including salts formed by reaction producing the dispersion. The salts tend to coagulate the dispersion and hence must be removed. Blood  ( a colloidal dispersion of plasma proteins) of patients with renal insufficiency has high concentration of urea and other metabolites. These as well must be removed to acceptable levels. Substances in true solutions may be separated from those in colloidal dispersion by means of dialysis or ultrafiltration.

Dialysis:

This is based upon the fact that colloidal particles do not diffuse (or diffuse very slowly) through membrane of parchment, cellophane, collodion or certain animal tissues, while particles of molecular or ionic dimensions diffuse relatively rapidly. Thus if  the low  molecular weight impurities are to be removed from a colloidal dispersion the latter is placed inside a sac made of one of the above mentioned membranes and dipped in water. The small solutes will diffuse out while pure colloidal materials are retained.

The rate of dialysis is increased increasing the area of membrane (e.g. using numerous hollow fibres, stirring and maintaining a high concentration gradient (dialysis fluid must be replenished continuously). If the impurities are electrolytes, the dialysis process can be speeded up by applying an electric potential to the sol. The process is then known as electrodialysis, and the equipment used is electrodialyser. Application of pressure in a dialytic process also speeds up the process. This is known as ultrafiltration.

Application of dialysis.

Dialysis is used in the laboratory to purify sols and study binding of drugs by proteins, as well as in some manufacturing process. The blood in uremic patients is dialysed  to remove urea, creatinine, uric acid, phosphates and other metabolites. The dialyzing fluids contain Na⁺, Cl^- , KCl, Acetates, dextrose etc in same concentration as plasma. Urea, creatinine, uric acid, phosphates and other metabolites diffuse from blood side to dialysis fluid until their concentration equilibrates to that in blood. NaCl, KCl diffuse at initial high concentration until equilibrium. The volume of dialysis fluid is much higher than that of blood to ensure complete removal of unwanted metabolites and is continuously replenished. Plasma proteins and blood cells do not pass out because of their big size. Edema is relieved by vacuum pressure. The process is known as haemodialysis. It is also employed in cases of acute poisoning.

OPTICAL PROPERTIES OF COLLOIDS, Faraday-Tindall effect

If a narrow beam of light is passed through a colloid, its path is visible. This is not possible with true solutions. The visible cone seen is due to light-scattering action by the colloidal particles and is known as the Faraday-Tindall effect.

The Faraday-Tindall effect is employed in the ultramicroscope and electron microscope. In the ultramicroscope an intense beam of light is passed through a sol against a dark background at right angle to the plane of observation. The particles are observes as bright spots and can be counted. For Better resolution, an electron microscope is used and very minute particles (molecular level) can be observed in terms of size, shape, and structure. The electron microscope uses a beam of high-energy electrons instead of the normal light.

The light scattering property is also used to determine the concentration of sol through measurement of turbidity, a phenomenon known as turbidimetry. Turbidity, τ, is a fractional decrease in intensity due to scattering as the incident light passes through a solution.

                        τ  = 1 ln Is

                               l      I    Where l = length of dispersion through which the light

passes

                                                                 Is = Light scattered in all directions

                                                                 I  =  Intensity of incident light

If the turbidity of suspension of known concentration is determined, the concentration of a certain value can be determined.

We can also use turbidity to measure molecular weight.

                       

 Hc / τ = 1/M +2Bc   Where H and B  are constants of a particular system,

                        c is concentration and M is the molecular weight.

STABILITY OF COLLOIDS

Effect of added electrolytes on ζ

The addition of electrolytes to a colloidal system reduces zeta potential or even reverses it. The electrolytes supply additional anions and cations so that the density of ions of opposite charge to the charge on the wall is increased. Thus the ionic atmosphere is compressed near the surface and the potential gradient in the fixed layer is greatly increased and the potential in the diffuse layer (as well as the zeta potential) is decreased. As the concentration of the counterions in the liquid increases, the ζ is continuously reduced tending to zero, and may even be reduced. The higher the valence of the electrolyte, the higher the reduction of potential. Thus trivalent ions are more effective than divalent ions, which are in turn more effective than monovalent ions.

The presence and magnitude or absence of charge on colloidal particles is an important factor in stability of colloidal systems. However, lyophilic and lyophobic colloids differ in their stability requirements and hence each is approached separately.

Stability of lyophobic colloids

A lyophobic sol is thermodynamically unstable. It is produced from insoluble substances which have been subdivided as polymolecular aggregates throughout the liquid phase. The enormous increase in surface area results in an increase in surface energy. Particles therefore have a tendency to aggregate and precipitate in order to reduce this energy. The tendency to aggregate is offset by the repulsive forces between particles due to the charge at the surface of the particles. Not however that there exist Van der Waal forces of attraction between particles. Thus there are two opposing forces between any two colloidal particles, attraction and repulsion.

Forces acting between two particles in colloidal sol

Consider two particles in close proximity. They attract each other by Van der Waals forces of attraction which vary inversely as x⁷ ( where x = distance between them). The particles also repel each other due to electrostatic forces which vary inversely as x2. The resultant force between the particles as a function of their distance apart was explained independently by Derjaguin and Landau in the USSR and by Verwey and Overbeek in the Netherlands in the early 1940’s. This is now called DLVO theory, and is summarized in the following figure:

Consider two particles approaching each other. Curve A represents the Van der  Waals attractive energy (which decrease with second power of the inter-particle distance). Curve R represents the electrostatic repulsive forces (which decrease exponentially with the seventh power of the inter-particle distance). The combination of these two opposing forces, attraction dominates at large distance and shallow trough is exhibited at x₃. This so-called secondary minimum is significant in controlled flocculation in preparation of suspensions.. As the particles still approach each other, repulsion begin to dominate at intermediate distance, to reach maximum at x₂, so called primary maximum. Repulsion occurs because when particles approach each other the two atmospheres of counterions surrounding them begin to interpenetrate or overlap at point o_. Repulsion occurs because of the work involved in distorting the diffuse double layer and in pushing water and counterions aside, which increase as the particles approach further to reach maximum at point x_2. At this point the potential energy barrier exceeds the kinetic energy of the approaching particles, and the particles will not come close to each other, and the dispersion shall be stable. But if the kinetic energy exceeds the potential energy, at x₂ or beyond, the particles continue to approach each other past this point, where van der Waals forces of attraction become more important than the repulsive forces_. The net potential energy decrease to zero and then becomes negative as the particles continue to approach each other, until when they touch at point a (x₁) otherwise known as primary minimum. This corresponds to a very stable situation in which particles adhere, and are attached permanently (irreversible caking in suspensions). In other words, the particles agglomerate or the sol is said to coagulate. This situation is irreversible because no kinetic energy can be applied to overcome the potential energy. In practice the particles cannot approach further than this point, but theoretically, if the particles were to approach further than the touching distance, they will meet with very rapid rise in potential energy, because they will be interpenetrating each other, causing the atomic orbitals to overlap and face repulsive Bonn repulsive forces.

Addition of Electrolytes decrease the height of the primary maxima and the range over which the electrostatic repulsion is effective, and hence lead to coagulation. The lowest concentration at which an electrolyte coagulates the sol is called coagulation value, C_v. It does not depend on valence of the anion, but depends on the valence of the counterions, decreasing by one or two orders of magnitude for each increase in heir valencies. This is the Schulze-Hardy rule.

Effects of added solvents:

The addition of water miscible solvents e.g. alcohol, glycerin, propylene glycol or polyethylene glycol (to aqueous dispersions) lowers the dielectric constant ε of the medium. This reduces the thickness of the double layer and therefore the range over which electrostatic repulsion is effective, and lowers the size of potential energy barrier. Thus addition solvents to aqueous dispersion lead to coagulation. At concentration to low to cause coagulation, solvents make dispersions more sensitive to coagulation by added electrolytes, i.e. they lower the C_v

Stabilization by adsorbed surfactants:

Recall that surfactant molecules are amphiphiles having  a polar and non-polar parts. When placed in a medium of dispersed system, they accumulate at interfaces and orient themselves in such a way that the hydrocarbon (non-polar) part is in contact with non-polar particles or oil droplets while the polar group is oriented towards the polar (usually water) phase. This is known as oriented physical absorption. The adsorption of ionic surfactants increases the charge density and the zeta potential ζ of disperse particles. This in turn increases electrostatic repulsion among non-polar organic particles and hence stabilization of the system. This is known as charge stabilization.

Water-soluble non-ionic surfactants are usually hydrated making the particle surface where they are adsorbed to be surrounded by a thin layer of water. This hydrophilic shell forms a steric barrier which prevents close contact between particles and hence coagulation. This known as steric stabilization. Moreover, non-ionic surfactants reduce the sensitivity of hydrophobic sols towards coagulation by salts, i.e. they increase the coagulation value Cv_.

Surfactants added to a flocculated sol tend to pry apart the flocs by wedging themselves between the particles and their area of contact. This allows in more surfactant molecules and hence breaks-up the flocs. The system becomes deflocculated or undergoes peptization.

Peptization is defined as formation of colloidal dispersion by action of solvent i.e. breaking up of large particles into colloidal range. Peptization can be spontaneous e.g. albumin and water form a “solution” due to extensive solvation. But some action may be needed to bring about peptization. E.g. precipitated substances may be brought into colloidal dispersions either by providing a peptizing agent usually a surfactant, or by removing a flocculating agent similar to deflocculation). When activated charcoal is added to water with stirring, grains are broken up incompletely. The suspension is no good. Addition of 0.1% sodium laurylsulphate or octoxynol disintegrates the particles to fine ones and the dispersion changes color from gray to deep black. Alumium hydroxide Al(OH)₃ in the presence of aluminium chloride (AlCl₃) is a poor colloidal dispersion. Washing with water removes AlCl₃ and a good colloidal dispersion forms.

Ophthalmic and parenteral suspensions should be deflocculated to prevent irritation and capillary blockage respectively. But because deflocculated systems tend to cake, a process of controlled flocculation is used in preparing such suspensions.

Stabilization by adsorbed polymers;

Water-soluble polymers act like surfactants and are adsorbed at interface. The polar part attracts and encloses water of hydration forming a sheath that surrounds the particles. This layer is part of the particles and prevents the particles from touching each other to coagulate. This kind of steric stabilization is said have protective action. The sol thus protected has resistance to coagulation by salts. The water-soluble polymers whose adsorption stabilizes hydrophilic sols against coagulation are called protective colloids, e.g. gelatin, serum albumin, povidone and dextran. The stabilizing efficiency of a protective colloid is determined by its gold number. (define the gold number of  a polymer)

 

Some protective colloids at concentrations below those at which they exert a protective action may cause sensitization, i.e. a decrease in the stability of hydrophobic sols.

ELECTROKINETIC PHENOMENA

Electrokinetic phenomena include Electrophoresis, electrosmosis, sedimentation potential and Streaming potential, whereby a potential is created when charged particles move with respect to a stationary liquid or particles move upon application of a potential. The phenomena are evidence that particles are charged. 

Electrophoresis:

When a dc electric field is applied to a dispersion, the particles move towards the electrode of a charge opposite to that on their surface. The counterions located inside their hydration shell are dragged along. The counterions in the diffuse layer outside the plane of shear will move towards the other electrode. This phenomenon is called electrophoresis. The rate of migration of particles is observed by means of an ultramicroscopic and is a function of the charge on particle. As mentioned earlier, the potential at the plane of shear is the Zeta potential. The sign and magnitude of zeta potential can be measured from a knowledge of the direction and rate of migration.

ζ =       ν  x  4πη  x (9 x 10⁴)

E       ε

Where ν is the velocity of migration (cm/sec)

η = viscosity of the medium (poise), ε is the dielectric constant

E is potential gradient (volts/cm).

ζ  is in volts.

The expression v/E is known as mobility.

Sedimentation potential:

The reverse of electrophoresis, that is a potential is created when particles undergo sedimentation (against a stationary liquid).

Electrosmosis:

If a charged surface is immobile (e.g. a packed bed of particles), application of an electric field causes the counterions in the free water to move towards the opposite electrode, dragging the solvent with them. Thus the liquid moves relative to the stationary charged surface, and the phenomenon is known as electrosmosis. The pressure produced is the electroosmotic pressure. By determining the rate of flow of a liquid under standard conditions, Zeta potential can be measured.

Streaming potential

If the liquid is made to flow past a charged surface in a capillary tube by applying hydrostatic pressure, the displacement of the counterions in the free water produces a potential difference between the two ends of the tube or bed. This potential is known as Streaming Potential. Measuring this potential, Es, and knowing the applied pressure, P, we can obtain from zeta potential from the following equation:

ζ =   4πηκΕl

            εP

Where l = length of capillary, and κ is conductivity of liquid.

ELECTROKINETIC PROPERTIES OF COLLOIDS

Particles in a liquid medium may become charged. Because of this charge on the surface of the particles, electro kinetic properties arise.

There are several ways in which a colloidal particle may acquire a charge:

·         Selective adsorption of a particular ion species present in a dispersion or a solution. The ion may have been added to the solution or in the case of water, it may be the hydronium (H⁺) or hydroxyl (OH^-). Thus particles in water are negatively charged due to preferential adsorption of (OH^-) ions. Ionic surfactants are also adsorbed and impart corresponding charge.

·         Particles also acquire charge through ionization of groups or moieties at the surface. In proteins, one end of the polypeptide has carboxylic acid group (COOH) which ionize to give a negative charge. The other end group has amino group (NH₂) and ionize to give a positive charge. The predominating charge depends on the pH of the medium. Thus the particles may be negatively or positively charged or neutral. Similarly Aluminium hydroxide gel (Al(OH)₃) form Al³⁺ in acid and [Al(OH)]⁴⁺ in alkalis.

·         Non-ionizing particles may also acquire a charge due to a difference in dielectric constant between the disperse phase and the dispersion medium. The phase with a greater e acquires a negative charge.

Electric Double Layer.

Due to a charge on the particles in a colloidal sol, ions of opposite charge are attracted firmly to the surface of the charged particle to form a layer.  The ions of opposite charge further distribute themselves diffusely in  the vicinity of the particle to form a second layer. The two layers constitute a phenomenon known as the electrical double layer. Although the particle is charges, the system is electrically neutral, because the two layers described above neutralize each other.

In order to understand the electrical double layer better, let us follow an example of silver iodide sol. Silver iodide may be obtained in the following reaction:

------>AgNO₃ + NaI                         Ag I   + NaNO₃                            

If the reaction is carried out with excess AgNO₃ there will be excess Ag+ than I ^– ions on the surface of the AgI precipitate, and the particle will be positively charged. The NO₃^- ions will surround the particles and will form the first layer. Na⁺ and other NO₃^- ions will distribute diffusely to form the second layer of the electrical double layer. If on the other hand there were excess of NaI in the reactants, the surface would contain negative charge.

In the bulk of the particle, the two ions (Ag⁺ and I^-)are exactly I equimolar proportions. In the medium (water) where the particles are suspended, Na⁺ and NO₃^- ions dominate, and some I ^– , H⁺, OH^-  ions are also apparent.

The negative charge on the surface of the particle attracts positive ions from the solution, and repels negative ions. These I ^– ions adsorbed at surface are known as potential determining ions. They attract oppositely charged ions from the medium to the surface. Thus, Na⁺ are concentrated in the immediate vicinity of the surface and tend to stick to the surface, approaching it as closely as their hydration spheres permit. Na⁺ Ions in this respect are called counterions or gegenions. They form a compact layer called Stern layer.

NO₃^- ions are repelled, and together with some Na⁺, I ^–, H⁺, OH^- and Ag+ , due to thermal agitation of water, form a second diffuse layer called the Gouy-Chapman layer. The combination of the two layers of oppositely charged ions constitutes an Electric double layer.

The electric potential at the surface of the particle is equal to the work against electrostatic forces required to bring a unit electric charge from the bulk of the solution (infinity) to the surface of the particle, and is known as surface potential or Electrothermodynamic potential or Nernst Potential g₀. On moving away from the surface towards the bulk, the potential drops rapidly across the Stern layer (Na ions screen further removal of other Na ions in the diffuse part of the double layer).In the Gouy-Chapman layer, the drop of potential is more gradual, tending to zero asymptotically as the composition of cations and anions approach equilibrium. The thickness of the double layer has been arbitrarily assigned the value of 0.37g_o.

(0.37 = 1/e). It usually ranges from 10 – 1000 Å and decreases as the concentration of electrolytes in solution increases, more rapidly for counter ions of high valence.

In aqueous dispersions, particles are surrounded by a layer of water of hydration attached to them by ion-dipole and dipole-dipole interaction. When a particle moves, this shell of bound water and all ions located inside it move along with the particle. If on the other hand water in a solution flows through a fixed bed of these solid particles, the hydration layer surrounding each particle remains stationary attached to it. The electric potential at the plane of shear separating the bound water from the free water is the zeta potential, ζ. It is less than the Stern potential. Zeta-potential is of practical importance when compared to other potentials because it can be measured experimentally. It is important in the stabilization of dispersed systems since it governs the degree of repulsion between adjacent dispersed particles. If the zeta potential is reduced below a certain value, the attractive forces exceed the repulsive forces and the particles come together or undergo flocculation.