Colloidal Dispersion, Its Types and Method of Preparation

Dispersion
Definition of Colloids
Shapes and Sizes of Colloids
Classification of Colloids
Properties of Colloids
1. Optical Properties.
2. Electrical Properties.
3. Kinetic Properties
Purification of Colloids
Method of Preparation of Colloids.
Physical Stability of Colloids.
Factors affecting Colloidal Dispersion.

1. Colloidal Dispersions Ms. Chitralekha G. Therkar Assistant Professor Dept. of Pharmaceutics, Siddhivinayak College of Pharmacy, Warora

2. Dispersed Systems Dispersed systems consists of particulate matter (API) i.e. dispersed phase which is distributed throughout a continuous phase i.e. dispersion medium . These systems are classified according to the mean particle diameter of the dispersed material, Colloidal Dispersion (0.5 µm to 1 µm or 500 nm to 1000 nm) Particles which cannot resolved by simple microscope but can be detected by an electron microscope. The particles of this systems can pass through filter paper but cannot pass through the Semi Permeable Membrane due to small pore size. The particles of this systems are made to settle by the centrifugation method as they cannot settled down directly by gravity. They diffuse very slowly. These types of colloids shows light scattering when passes a beam of light. They are generally of turbid appearance. The colloids shows Brownian Motion (shows random and irregular movement) Egs, Colloidal silver sols, natural and synthetic polymers .

3. 2. Coarse Dispersion (10 - 1000 µm) The particles of this systems are visible by ordinary light microscope . They do not pass through the filter paper or the SPM. The particles are settled down by gravity . The particles do not diffuse and shows very negligible brownian motion. These dispersed systems are opaque in appearance. The coarse dispersions shows light scattering when subjected in front of beam of light. Egs, Emulsions, Suspension and RBC’s . 3. Molecular Dispersion (LT 0.01 µm) The particles of this system are invisible in electron microscope . They can pass through the filter papers as well as SPM . The particles of this system do not settle down on standing. They undergo rapid diffusion. These systems have very clear appearance. The dispersed systems shows brownian and kinetic motions. They do not show light scattering. Egs, Ordinary ions, Glucose, Urea, Oxygen .

4. Colloidal dispersions The term colloid is derived from two words i.e. ‘kolla’ meaning Glue and ‘eoids’ meaning Like which means glue like substances . Colloidal dispersions are the heterogeneous dispersed systems, where an internal phase (dispersed particles) are distributed uniformly in a continuous or external phase (dispersion medium) and the system have particles size range from 0.5 – 1 micron . The fluid colloidal systems which are composed of two or more components within them, they are called as sols . In colloidal systems, particles pass through filter paper but cannot pass through semipermeable membrane and they diffuse very slowly. Egs, Gums (acacia, tragacanth), Natural rubbers etc. Some colloids encountered in pharmacy includes surfactant micelles, suspensions, emulsions, inhalation aerosols etc.

5. Sizes and shapes of colloids Particles existing in colloidal dispersion have large surface area when compared with the surface area of an equal volume of larger particles which means once a normal particle is incorporated as a colloid its surface area gets increased. This enhanced surface is called as Specific surface . Specific surface – the surface area of that system per unit weight or volume of material . And this possession of large specific surface results in, Additional effect – Eg, platinum is a normal metal until it is incorporated as colloid. Once it get dispersed as colloid, it acts as an effective catalyst which have quite large surface area than normal platinum and which can adsorb reactants on their surface. Coloration after increase in size – the colour of colloidal dispersion is related to the size of particle, as the size of colloidal particles increases, they starts imparting a colour within system. Eg, Red gold sol takes a blue colour when the particles increases in size. Size

6. 2. Shapes The shape adopted by colloidal particles in dispersion is important because the more extended the particle, the greater is its specific surface and the greater is the attractive forces between the particles of the dispersed phase and dispersion medium. In a friendly environment, a colloidal particle unrolls and exposes maximum surface area. Under adverse conditions, it rolls up and reduces its exposed area. Shape of colloidal particles can affect the flow and sedimentation of that colloidal system and sometimes it may influence the pharmacological action. The shapes that can be assumed for colloidal particles are, Spheres and globules Short rods and prolate ellipsoids (rugby ball shaped/elongated) Oblate ellipsoids (disc shaped/flattened) and flakes. Long rods and threads. Loosely coiled. Branched threads. The following properties are affected by changes in the shape of colloidal particles, Flowability Sedimentation Pharmacological action.

7. Classification of Dispersed systems 1. Based on the physical state of two phases. SN Dispersed phase Dispersion Medium Colloid Type Examples 01 Liquid Gas Liquid aerosol Cloud, mist, fog 02 Solid Gas Solid aerosol Dust, smoke 03 Gas Liquid Foam Whipped cream 04 Liquid Liquid Emulsion Milk, Mayonnaise 05 Solid Liquid Suspension Jelly, paint 06 Gas Solid Solid foam Pumice, marshmallow 07 Liquid Solid Solid emulsion Cheese, butter 08 Solid Solid Solid sols Pearls, opals

8. 2. Based on the interaction between colloidal phases Lyophilic colloids Lyophobic colloids Association colloids

9. Lyophilic colloids In this system, the dispersed particles have a greater affinity towards the dispersion medium used for formulation ( solvent loving ). These systems are called as Hydrophilic when solvent is water and Lipophilic when solvent is Oil. They are called as Oleophilic when solvents are Non Aqueous vehicles . The dispersion medium forms a sheath around the colloidal particle and solutes. This makes the dispersion thermodynamically stable. As these systems are thermodynamically stable they are reversible , they can be reconstituted after the solvent is removed from the system. Lyophilic colloids are usually obtained simply by dissolving the material in solvent being used for formulation and for this reason, preparation of lyophilic colloids is relatively easy.

10. Generally organic material is used to dispersed in the dispersion medium. Various properties of this class of colloids are due to the attraction between the dispersed phase and dispersion medium, which leads to solvation , the attachment of solvent molecules of the dispersed phase to solutes (if water is solvent or dispersion medium it is termed as Hydration) Eg, the dissolution of acacia or gelatine in water leads to formation of a solution . Preparation of Lyophilic Colloids – The simple dispersion of lyophilic material in a solvent leads to the formation of lyophilic colloids. Firstly the colloidal particles to be constituted are crushed with solute or DP to get uniform size. Then the required solvent or DM is added slowly and with continuous stirring until the dispersion is formed.

11. 2. Lyophobic colloids Colloids are composed of materials that have a little attraction between the dispersed phase and dispersion medium (solvent hating) or sometimes no attraction at all. These systems are stable because of presence of charge on particles , colloids are generally composed of inorganic particles dispersed in water such as salts of gold, silver, silver iodide etc. These lyophobic colloids and their properties differs from the lyophilic colloids by not having a solvent sheath around the particles and it is necessary to use special method to prepare lyophobic colloids which are given as follows, Preparation of lyophobic colloids – 1. Dispersion method – This method involves the breakdown of larger particles into particles of c olloidal dimensions. The breakdown of coarse material may be affected by the use of the c olloid mills, u ltrasonic treatment in presence of stabilizing agent s like, surface active agent.

12. 2. Condensation method – In this method, the colloidal particles are formed by the aggregation of smaller particles such as molecules. These involves a high degree of initial supersaturation followed by the formation and growth of nuclei. Supersaturation can be brought about by, Change in solvent For example, if sulfur is dissolved in alcohol and then this concentrated solution is poured into an excess of water, many small nuclei form in the supersaturated solution. These grow rapidly to form a colloidal sol. If a saturated solution of sulphur in acetone is poured slowly into hot water the acetone vaporizes, leaving a colloidal dispersion of sulphur. Chemical reaction For example, colloidal silver iodide may be obtained by reacting together dilute solutions of silver nitrate and potassium iodide. If a solution of ferric chloride is boiled with an excess of water produces red sol of hydrated ferric oxide by hydrolysis. 3. Milling and grinding method – generally mortar and pestle, sieves etc are used in small scale. 4. Super saturation method - Eg, sulfur is dissolved in alcohol and then the concentrated solution is transfer to water, small nuclei will produced these grow rapidly to form colloidal solution

13. Lyophilic colloids Lyophobic colloids Colloidal particles have greater affinity for the dispersion medium. Colloidal particles have little affinity for the dispersion medium. Owing to their affinity for the dispersion medium, the molecules disperse spontaneously to form colloidal solution. Material does not disperse spontaneously , and hence lyophobic sols are prepared by dispersion or condensation methods. These colloids form “ Reversible sols ” These colloids form “ Irreversible sols ”. Viscosity of the dispersion medium is increased greatly by the presence of colloidal particles. Viscosity of the dispersion medium is not increased by the presence of colloidal particles. Dispersions are stable , generally in the presence of electrolytes, they may be salted out by high concentrations of very soluble electrolytes. Lyophobic dispersions are unstable in the presence of even small concentrations of electrolytes because they already have charges. Dispersed phase consists generally of large organic molecules such as gelatin, acacia lying within colloidal size range. Dispersed phase ordinarily consists of inorganic particles , such as gold or silver. Comparison of Lyophilic and Lyophobic colloids

14. 3. Association colloids Surface active agents have two distinct regions of opposing solution affinities within the same molecule or ion and are known as Amphiphiles . When present in liquid medium at low con centration, the amphiphiles exist separately and in subcolloidal size. As the concentration of them is increases, the aggregation occurs over a narrow concentration range. These aggregates which may contain 50 or more separate monomers, are called as Micelles . Because the diameter of each micelle is of the order of 50Å, micelles lie within the colloidal Size range . The concentration of monomer at which micelles are formed is termed as Critical Micelle C oncentration (CMC) . The number of monomers that aggregate to form a micelle is known as the Aggregation number of the micelle. In water, the hydrocarbon chains of amphiphiles, faces inward into the micelle to form their own hydrocarbon environment. Surrounding this hydrocarbon core are the polar portions of the amphiphiles associated with the water molecules of the continuous phase.

15. The association colloid can be classified as anionic, cationic, nonionic and ampholytic (zwitter ionic) depending upon the charges on the amphiphiles. The opposite ions bound to the surface of charged micelles are termed counter ions or gegenions , which reduces the overall c harge on the micelles. The viscosity of the system increases as the concentration of the amphiphile increases because micelles increase in number and become asymmetric.

16. Optical properties of colloids When a strong beam of light is passed perpendicularly through two solutions , i.e. t rue solution and colloidal solution, w hich are placed against a dark background, The path of light beam is not visible in case of true solution. The path of light beam is visible (scattered) in case of colloidal solution and further it is forming a shadow (beam or cone) at the dark background. In case of colloidal sols, some of the light gets absorbed, some gets scattered and remaining gets transmitted through the sample. And due to the light scattering, the sol appears turbid, and this phenomenon is called as Faraday – Tyndall Effect. The illuminated beam or cone formed by the sol particles is called Tyndall beam or Tyndall cone. 1. Faraday Tyndall Effect

17. 2. Light Scattering effect This is based on Faraday - Tyndall effect. I t is widely used in the determination of s ize, shape and interactions of the colloids. As the turbidity depends upon the size of particles dispersed, it is used in determining the molecular weights of colloids. Principle – Scattering is expressed in terms of turbidity τ, the fractional decrease in the intensity due to scattering as the incident light passes through 1 cm of solution. The turbidity can be calculated as follows , τ - turbidity in cm -1 , c - concentration of the solute in gm/cm 3 M=weight of the average molecular weight in g/mol B – Interaction constant, H – Optical constant depending upon Refractive Index

18. 3. Ordinary light microscope – The light microscope which uses light as its source of radiation resolves particles separated by a distance of 1800 A or may be MT that. But the limitation of this light microscope is that it used to resolve only particles ranging in above particle size range. 4. Electron microscope – the electron microscope uses a beam of accelerated electrons as a source of light. These microscopes have a higher resolving power than light microscope and can be use to reveal the structure of smaller objects. There are Two types of electron microscopes, Transmission Electron Microscope – it uses high voltage electron beam which is produced by an electron gun fitted with tungsten filament. Scanning Electron Microscope – this method produces image by probing the specimen with a focused electron beam . When this beam of electrons interacts with the specimen, it loses its energy and the image is displayed by the SEM Maps. Applications – Particles size analysis Particle detection Material qualification Research and Development

19. Kinetic properties of colloidal system Kinetic properties of colloidal systems relate to the motion of particles with respect to the dispersion medium. The motion may be thermally induced (Brownian movement, diffusion, osmosis) or gravitational force induced (sedimentation) or applied externally (viscosity). The kinetic properties are, 1. Brownian motion 2. Diffusion 3. Osmotic pressure 4. Sedimentation 5. Viscosity 1. Brownian motion Colloidal particles undergo random collisions with the molecules of dispersion medium and follows an irregular zigzag path . If the particles up to 0.5 µm diameter are observed under the microscope or the light scattered by colloidal particles is viewed using an ultra microscope, an erratic motion is seen. This movement is referred to as Brownian motion . The motion of molecules cannot be observed. The velocity of the particles increases with decreasing the size. If added the viscosity agent brownian motion stops. It arises as the consequences of Kinetic Theory.

20. 2. Diffusion - As a result of brownian motion, colloidal particles spontaneously diffuse from a region of higher concentration to lower concentration. The rate of diffusion is expressed by Fick's first law, = - DS According to the law, dM is the amount of substance diffusing in per unit time dt across a plane of area ( S ) is directly proportional to the change of concentration dc, with distance traveled dl . D is diffusion coefficient and has dimension of area per unit time, dc/dl is concentration gradient . The negative sign denotes that the diffusion takes place in a direction of decreasing concentration. The diffusion coefficient of a dispersed material is given by Stokes - Einstein equation, D = Where, N - Avogadro’s number (6.023×10 23 molecules per mole), R - molar gas constant and r is the radius of spherical particle at viscosity. The analysis of above equations allows us to formulate three main rules of diffusion, The velocity of molecules increase with reduction of particle size. The velocity of molecules increase with increasing temperature. The velocity of molecules decrease with increasing viscosity of the medium.  

21. 3. Osmotic Pressure Osmosis is the spontaneous movement of solvent molecules through SPM into a region of higher solute concentration in a direction that tends to equalize the solute concentration on both sides. The external pressure required to be applied so that there is no net movement of solvent across the membrane is called Osmotic Pressure . The osmotic pressure 𝜋, of a dilute colloidal solution is described by the Van't Hoff equation, 𝜋 = 𝑐𝑅𝑇 Where, c - molar concentration of solute, R – gas constant and T – temperature. This equation can be used to calculate the molecular weight of a colloid in a dilute solution. Replacing c with cg/M in above equation, in which ‘ cg’ is the grams of solute per liter of solution and ‘ M’ is the molecular weight , then we obtain, 𝜋 = RT = The above equation is true when the concentration of colloids is low (ideal system). For linear lyophilic molecules or high molecular weight polymers , f ollowing equation is valid.  

22. = RT B C g Where , B is an interaction constant for any solvent/solute system. And the plot of vs C g is linear. C g The extrapolation of line to the vertical axis where C g = 0 gives RT/M and if the temperature at which the determination was carried out is known, the molecular weight of solute can be determined. From the slope of the line, the value of interaction constant (B) can be determined. Line II indicates linear colloid in which the solvent have high affinity for the dispersed particles. Line I is observed for the same colloid if it is present in a relatively poor solvent having a reduced affinity for the dispersed material.  

23. 4. Sedimentation The velocity, v , of sedimentation of spherical particles having a density ρ, in a medium of density ρ and a viscosity η is given by Stoke's law, 𝑣 = Where ‘ g’ is the acceleration due to gravity. If the particles are subjected only to the force of gravity, then the lower size limit of particles obeying Stokes's equation is about 0.5 µm. This is because Brownian movement becomes significant and tends to offset sedimentation due to gravity and promotes mixing instead. Consequently, a stronger force must be applied to bring about the sedimentation of colloidal particles . In a centrifuge, g is replaced by ω 2 x, ω - angular velocity or angular acceleration 2 times the speed of rotor in revolution per second, x is the distance of particle from the center of rotation then the equation becomes, 𝑣 =  

24. 5. Viscosity Einstein equation of flow for the colloidal dispersions of spherical particles is given by, η = η (1 + 2.5 ϕ ) Where, ‘η ’ is the viscosity of dispersion medium, ‘ η’ is the viscosity of dispersion when volume fraction of colloid particles is ϕ. The volume fraction is defined as the volume of the particles divided by the total volume of dispersion . Relative viscosity (η rel ) = = 1 + 2.5 ϕ Specific viscosity ( η Sp ) = - 1 = 2.5 ϕ By determining η at various concentration and knowing η the specific viscosity can be calculated .  

25. Electrical properties of Colloids 1. Electrical double layer - The theory of the electric double layer deals with the distribution of ions and the magnitude of an electric potentials that occur in the locality of the charged surface. Consider, a solid charged surface in contact with an aqueous solution of an electrolyte. Suppose, some of the cations are adsorbed onto the solid surface (aa’) giving it a positive charge and these are called potential determining ions . Then the counter anions are attracted to the positively charged surface by electric forces and forms a region called tightly bound layer . In this layer there are fewer anions than cations adsorbed onto the solid surface and hence the potential at bb’ is still positive.

26. At a particular distance from the surface, the concentration of anions and cations are equal and form an electrically neutral region. The whole system is electrically neutral even though there are regions of unequal distributions of anions and cations and the region bounded by the bb’ and cc’ interface is called diffuse second layer where an excess of anions are present. Beyond cc’, the distribution of ions is uniform and an electrically neutral region exists and the potential at the solid surface is called Nernst potential and is defined as the difference in potential between actual solid surface and the electrically neutral region of the solution . The potential at plane bb’ is called Z eta potential and is defined as the difference in potential between surface of tightly bound layer and the electrically neutral region of the solution . Conditions – If zeta potential falls below a particular value (+30mV or -30mV), the attractive force exceed the repulsive force and results in aggregation of colloidal particles. 2. Zeta potential decreases more rapidly when the concentration of electrolytes is increased or the valency of counter ions is higher.

27. 2. Electrophoresis – The movement of particles inside a liquid or a gel medium where they are suspended under the influence of an electric field is called as Electrophoresis. The movement is expressed in terms of velocity, and the velocity of particles is dependent on following factors, Strength of electric field The viscosity of medium The velocity of a particle in an electric field is commonly referred as Electrophoretic Mobility (U E ), Zeta Potential ( ξ ) of the particle is calculated by using Henry’s Equation, U E = Where, is dielectric constant is Viscosity F(Ka) is Henry’s function.  

28. 3. Electro osmosis The movement of a liquid relative to the stationary charged surface under the influence of an electric field is called as Electro – Osmosis. If the sol is enclosed by compact diaphragms, then the motion of the sol particles be mechanically prevented. Two electrodes are inserted in the dispersion medium outside the diaphragms, the dispersion medium moves through the diaphragm towards one of the electrodes.

29. 4. Donnan Membrane Equilibrium – It is the behavior of charged particles near a SPM that sometimes fails to distribute evenly across the two sides of the membrane. The usual cause is the presence of different charged substances that is unable to pass through the SPM and thus creates an uneven electric charge. Eg, The large anionic proteins in blood are not permeable to capillary walls due to small cations attached to proteins. But the cations are not compulsorily attached to all proteins so, some of the proteins are passable from SPM.

30. Physical stability of colloidal systems The presence or absence of a charge on a colloidal particle is an important factor in the stability of colloidal systems. Stabilization is accomplished essentially by two means, Providing the dispersed particles with an electric charge. Surrounding each particle with protective solvent sheath that prevents mutual adherence when the particles collide as a result of b rownian movement. This second effect is significant only in the case of lyophilic sols.

31. The addition of an electrolyte to lyophilic colloid in moderate amount does not result in coagulation . If sufficient salt is added, agglomeration and sedimentation of the particles may result. This phenomenon referred as “Salting out” In general , lyophilic colloids are stable because of the solvent sheath around the particles. At high electrolyte concentration, ions get hydrated and water is no more available for hydration of particles. This results in flocculation or salting out of colloidal particles. 1. Effect of an electrolyte on Lyophilic colloids 1. Effect of an electrolyte

32. 2. Effect of an electrolyte on Lyophobic colloids A lyophobic sol is thermodynamically unstable. The particles in such sols are stabilized only by the presence of electric charges on their surfaces . The like charges produce a repulsion that prevents coagulation of the particles. Hence, addition of a small amount of electrolyte to a lyophobic sol tends to stabilize the system by imparting a charge to the particles. In colloidal dispersions frequent encounters between the particles occurs as a result of brownian movement. Such interactions are mainly responsible for the stability of colloids. There are two types of interactions, van der w aal’s attraction and electrostatic repulsions. When attractions predominate , the particles adhere after collisions and aggregate is formed and when repulsions predominate , the particles rebound after collisions and remain individually dispersed.

33. 2. Peptization The stability of colloids is due to following reasons, Development of electric charge on surface of colloidal particles. Formation of solvent sheath by the process of salvation. Brownian motion Origin of surface charge – the surface charges originates from following, Ionization of surface groups. Differential loss of ions from the crystal lattice. Adsorption of charged species.

34. When negatively and positively charged hydrophilic colloids are mixed, the particles may get separated from the dispersion to form a layer which is rich in the colloidal aggregates. These colloid rich layer is known as a “ Coacervate” , and the phenomenon in which macromolecular solutions separate into two layers is referred to as “ Coacervation” As an example, consider the mixing of gelatin and acacia. Gelatin at a pH below 4.7 (Isoelectric point) is positively charged and acacia carries a negative charge, that is relatively unaffected by pH in the acid range, When solutions of these colloids are mixed in a certain proportion, coacervation results. 3. Coacervation

35. 4. Protective Colloid Action When a large amount of hydrophilic colloid carrying opposite charge, is added to hydrophobic colloids, these gets adsorbed on the hydrophobic particles and form a protective layer around it . This adsorbed layer prevents the precipitating ions reaching the sol particles. Therefore, the further coagulation is prevented and the system becomes stabilized. The entire colloid behaves like a hydrophilic colloid. The colloid that helps to stabilize the other colloid is known as Protective C olloid .

36. The ‘protective property’ is expressed most frequently in terms of the “ Gold number” . The gold number is the minimum weight in milligrams of the protective colloid (dry weight of dispersed phase) required to prevent a color change from red to violet in 10 mL of a gold sol on the addition of 1 mL of a 10% solution of sodium chloride . The gold numbers for some common protective colloids are as follows, Gelatin (gold number 0.005-0.01) Albumin (gold number 0.1) Acacia (gold number 0.1-0.2) Basically, gold sol is a hydrophobic colloid and has red color. When an electrolyte like NaCl is added , coagulation of colloid is observed indicating violet color. When protective colloids are added, these stabilize the gold sol and prevent the change to violet color. Lower the gold number, greater the protective action.

37. Brownian motion Electrostatic forces of repulsion Van der Waals forces of attraction. Solvent on approach of neighboring particles (repulsion or attraction) General factors affecting the Stability of colloids

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