Colloidal dispersion

Contents Describes as per PCI

1. Colloidal Dispersion Presents – Mr.D ipak Bhingardeve Assistant Professor Department of Pharmaceutics

2. Colloidal Dispersion Definition – Colloidal dispersions are defined as those polyphasic system where at least one dimension of the dispersed phase measures between one nm and one micrometer. Diagrams-

3. Cont.. Also , Colloids is heterogeneous dispersed system in which one substance is divided into minute particles (colloidal particle) and dispersed throughout a second substance( usually liquid). This mixture is also called a colloidal system.

4. Official preparations A) Iron dextran Injection, BP- B) Iron Sorbitol injection, BP- Applications – 1)Better compliance – 2)Excipients- 3)Targeting of drug to specific organs – 4)Therapy – 5)Absorption and toxicity- 6) Solubility – 7)Stability- 8) Coating Agents- 9) Colloidal drug delivery system-

5. Classification of Colloidal Dispersions Colloidal systems are classified into two types- Positive and Negative colloids, depending on the charge that the dispersed particles possess. I) Based on Dispersion medium II) On the basis of interaction Between colloidal phases . a) Lyophilic Colloids b) Lyophobic colloids c) Association colloids

6. A) Lyophilic Colloids Lyophilic means solvent loving. The term indicate that dispersed particle have a greater affinity to the dispersion medium(solvent). The dispersion medium forms a sheath around the colloidal particles and solvates. This makes the dispersion thermodynamically stable, for this reason preparation of lyophilic colloids is relatively easy. Example- Acacia, gelatin , protein, starch etc. In water. Rubber in on-aqueous solvent like benzene forms lyophilic colloids.

7. b) Lyophobic Colloids: These are dispersion in which very little attraction is possible between the dispersed particles and dispersion medium. When dispersion medium is water they are called hydrophobic colloids. These are stable because of the presence of charge on particle. The like charges on particles keep them away from each other. However, solvent sheath around particle is absent, therefore these dispersion are thermodynamically unstable. Example- Gold sol, silver, colloidal sulphur in suitable solvent.

8. cont... C) Association colloids: These colloids are formed when molecule of soap or other surface active agent substances are associated together to form small aggregates ( micelles) in water. Colloidal aggregates are formed spontaneously when concentration of surface active agent exceeds critical micelles concentration. Above CMC, viscosity of system increases. Examples- Sodium lauryl sulphate, sodium stearate , cetyl trimethyl ammonium bromide etc.

9. Characteristics of dispersed phase Particle size Particle shape Surface area Surface charge Particle size: Particle size influence the colour of a dispersion . The wavelength of light absorbed by particle is approximately related to its radius. The larger the particle ,the shorter the wavelenghth of light transmitted. i.e violet end of spectrum. E.g Colloidal gold has a red colour ( 650 to 750 nm ), while intermediate size is in violet colour.

10. Particle shape: The shape of particles in dispersion depend on methods of preparation and affinity of the particles to dispersion medium. Shape also influence the colour of the dispersion . Spherical particles of gold is indicated by red colour , while disc like particles of gold gives blue colour. Spherical particle produce dispersion of low viscosity, while linear particles generally produce more viscous dispersion. Surface area: Size of colloidal particles is of order of few micrometers, these particle possess enormous surface area, when compared to coarser particle. The larger surface area enhances the solubility of drug particle.

11. Surface charge Depending on nature of dispersion medium and ions present in colloidal solutions ,colloidal particles acquire a charge on their surfaces. Colloidal particles possess charge on their surfaces. Surface charge provides valuable information regarding the stability of colloids. Particle move continuously in random manner with collisions with each other. The like charges on the particles create repulsion forces.

12. General characteristics of dispersion medium 1. Ease of Preparation- Lyophilic sols can be obtained straightway by mixing the material(Starch, Protein) with a suitable solvent. Lyophobic sols are not obtained by simply mixing the solid material with the solvent. 2. Charge on particle- Particles of hydrophilic sol may have little or no charge at all. Particles of a hydrophobic sol carry positive or negative charge which gives them stability. 3. Solvation – Hydrophilic sol particles are generally solvated. i.e they are surrounded by an adsorbed layer of the dispersion medium which does not permit them to come together and coagulate.

13. 4. Viscosity - Lyophilic sols are viscous as the particle size increases due to solvation, and the proportion of free medium decreases. Viscosity of hydrophobic sol is almost the same as of the dispersion medium itself. 5.Precipitation – Lyophilic sols are precipitated (or coagulated) only by high concentration of the electrolytes when sol particles are dissolved. Lyophobic sols are precipitated even by low concentration of electrolytes.

14. Streaming Potential Electrical Double layer Electron microscope Viscosity Sedimentation Osmotic Pressure

15. Optical properties This study helps in obtaining information regarding the shape , size, structure and molecular weight of colloids. The source of light and the resolving power of the optical system mainly determine the precision and usefulness of such information. When beam of light strikes a particle, it polarizes the atoms and molecules in it and induce dipoles in the particle. The dipole emit weaker light at the same wavelength as that of the incident light. The emitted light propagates in all direction. This phenomenon is called light scattering. 1. Tyndall Effect- It is observed due to interaction of particles with light. When an intense, narrow beam of light is passed through the dispersion of colloids, its path is visible ,due to scattered light.

16. Cont… This scattered beam is known as Tyndall beam. The same effect is noticed when a beam of sunlight enters a dark room through a slit when the beam of light become visible through the room. This happens due to the scattering of light by particle of dust in the air.

17. Sample is placed at the apex of cone ,where light intensity is high .after passing through the sample ,the cone of light diverges and passes outside incident light. Some scattered light enters the objective of the microscope. Ultra microscope is used to study the electrophoresis of charged particle, which helps in determining. Ultra microscope

18. 2.Elcteron microscope Particle size,shape and structure can be determined using an electron microscope. The radiation source is beam of high energy electrons having wavelength in the region of 0.1 A⁰. Electron microscope has high resolution power. Turbidity method is used to estimate the concentration of dispersed particles and molecular weight of the solute. Spectrophotometer- It measures the intensity of the transmitted light in the direction of the incident light. The relationship between turbidity & relative intensity of the transmitted light can be expressed as: I/I =e - tl where, I Intensity of incidence light, l-length of sample (1cm) I-intensity of transmitted light, t- turbidity

19. 3. Light Scattering It is used to study proteins, polymers, association colloids and lyophobic sols. Molecular weight of polymers and micelles can be measured. If the particles are spherical ,the scattering of light will be same in all directions. The turbidity is measured from scattered light by viewing at a particular angle. t = 16  R 90 3

20. Cont… Where , R90 = Ir 2 ( i.e. Rayleigh Ratio ) I I0 = Intensity of the scattered light I = Intensity of the incidence light r = Distance from scattered particle to the point of observation, mm. t = Turbidity

21. 3.Kinetic properties The study of kinetic properties of colloidal dispersion is useful in: a) Predicting the stability of the system. b) Determing the molecular weight of the particles. c) Studying the transport kinetics of colloidal particles. Following are various kinetic properties in colloids ; 1. Brownian motion- The scientist Robert Brown Who proposed this theory. Brownian motion may exhibited by particles as large as about 5 µm. Thermal energy keeps particles in motion. They collide with each other and with the walls of the container. These collision change the direction and velocity of particles.

22. Cont.. These molecular collision keep particles under continuous motion. Brownian movement can be viewed by a light microscope and works against gravitational force. Brownian movement can be decreased or stopped by increasing viscosity of the medium. i.e. by adding glycerin. 2 ) Diffusion - Particle diffuses spontaneously from region of higher conc to lower conc until conc of the system is uniform throughout. Diffusion is a direct result of Brownian motion. Diffusion can be expressed by Fick’s first law. As per Ficks first law the amount of substance (dq) diffuses in time dt across the plane area of A is directly proportional to the change of concentration dc with distance traveled, dx

23. Cont.. dq = - DA dc dt dx D is diffusion coefficient The measured diffusion coefficient can be used to determine the radius of particle or molecular weight. 3. Viscosity - The viscosity of colloidal dispersion is affected by a variety of factors. Shape of the dispersed particle- spherical particle impart relatively low viscosity to dispersion, while particles of linear shape yield more viscous systems.

24. Cont.. Affinity of particle to the medium : If linear particles are placed in a medium having low affinity for particles, these tends to assume spherical shape and the viscosity falls. Type of colloids : I n general ,lyophilic colloids have viscosities manyfold greater than that of the dispersion medium. Lyophobic colloids have viscosities almost equal to the dispersion medium. Viscosity is an expression of the resistance to flow of the system under an applied stress. The flow of dilute colloidal system is expressed by an equation developed by Einstein. n = n o ( 1 + 2.5 Φ ) where , n =viscosity of the dispersion medium

25. Cont… n= Viscosity of the dispersion . Φ = Volume fraction of particles. 4) Sedimentation : The velocity of sedimentation of spherical particle is obtained by stokes law. Sedimentation is influenced by the gravitational force. Stokes law applied to particles larger than 0.5 µm for applying the stokes law. Sedimentation is not kinetic property of the colloidal system by itself under normal condition. Therefore a stronger force must be applied to bring sedimentation of particles.

26. Cont… The velocity of sedimentation is given by V= d 2 ( ρ i - ρ e )g/ 18 n Where , V= rate of sedimentation D= diameter of particle ρ = Density of internal phase and external phase g = Gravitational constant n= viscosity of medium

27. 5) Osmotic pressure: Osmotic pressure of colloidal solution is a colligative property useful in determination of molecular weight of dispersed phase, Van’t Hoff equation used to determine the mol. wt of colloid in dilute solution specially polymer. Van’t Hoff equation  = cRT Where , c= conc of solute particles in g/L  = osmotic pressure exerted by colloidal particles. R= molar gas constant T= Absolute temperature

28. Cont.. Replacing c with C/M in equation.  = C g RT M  /Cg = RT/M Where, Cg = grams of solute per litre of solution. M= mol.wt .  = osmotic pressure R= Molar gas constant. Substituting values of experimental observations in this gives molecular weight of the colloidal particle.

29. Electrical Properties: 1 . Electrical double layer :/Surface charge : Let us consider very colloidal solution in which the surface of each solid particle preferentially adsorb positive charges from environmental aqueous solution containing positive and negative ions due to dissolve salts. A region existing at the boundary of two phases and assumed to consist of two oppositely charged  layers  (such as a  layer  of negative ions adsorbed on colloidal particles that attracts a  layer  of positive ions in the surrounding electrolytic solution) — called also Helmholtz  double layer

30. Electrical Double layer

31. Cont... The negative charges ion attracted to solid surface and positive ions repelled from solid surface . In addition to electric forces ,thermal motion within the medium also influences the distribution of ions which produce equal distribution of all ions in solution. As a result of these effect, diffuse layer of solution is created in which the concentration of negative ions gradually decreases and conc. of positive ions gradually increases up to a certain point in the layer. Where, number of positive and negative ions becomes equal . Thus, the particle are surrounded by a tightly bound layer (stern layer) of consisting of counter ions sticking to the surface of diffuse double layer. This type of distribution of charges surrounding the particle is called Electrical double layer.

32. Nerst and zeta potential Nerst potential : The difference between stern layer and potential produced on the surface layer is called Nerst potential. Zeta potential : The rate of movement of individual colloidal particle is a function of charges on particle and directly related to the zeta potential . The potential difference existing between the surface of a solid particle immersed in a conducting liquid (e.g. water) and the bulk of the liquid (solvate) called zeta potential. Stable suspension is range between +30 to -30 mv . If potential is electrodynamic= Nerst potential If potential is electrokinetic = Zeta potential.

33. 2. Electrophoresis: The movement of a charged particle which is relative t0 liquid it is suspended under influence of an applied electric field is called as Electrophoresis . Used to measurement of zeta potential. It is electrokinetic phenomenon . If an electric potential is applied to a colloid, the charged colloidal particles move towards the oppositely charged electrode. The charge on the particle determined and gives sign of zeta potential and rate of migration of function of charge on particles. Velocity or rate of migration increases with increasing potential gradients. V = ξ x E where , ξ = zeta potential,

34. 3. Electro-osmosis: Electro-osmosis is opposite principle to that electrophoresis . The atmosphere of counter ions around the particle confers a charge on the dispersion medium. + ve and – ve particle are present in liquid medium, they are move opposite pole. This flow of liquid medium under the influence of electric field is known as electro-osmosis, and pressure is called electro-osmotic pressure . 4 . Streaming Potential : This is opposite of electro-osmosis. If the electrodes in the electro-osmosis apparatus are replaced by galvanometer in the circuit, no current will be detected when the liquid is stationary. If the liquid is forced through tube the galvanometer measure current .

35. Cont... Streaming potential due to displacement of the charges equilibrated in the double layer around the solid. This technique can be used to measure the zeta potential of relatively coarse solids which would sediment rapidly on electrophoresis cell.

36. 5. Sedimentation potential/ Donnan Membrane Equilibrium: This is the potential difference set up between top and bottom of a suspension of solid particles in a liquid when the particles settle under the influence of gravity. Principle : A solution of NaCl is placed on one side of the semipermeable membrane. On the other side a solution of negatively charged colloids together with its counterion is placed. The volume of solution on the two side of membrane are considered to be equal. Na+ and Cl - ion move freely across the semipermeable membrane, but colloidal particles, colloidal particles (R-) are not diffusible soon equilibrium is attained.

37. Cont.. Apply the condition of electroneutrality . i.e. The + ve and – ve charge on either side of the membrane must be balanced. At equilibrium, the osmotic pressure of two solutions will be different and if two reference electrodes such as calomel electrodes are put into the two solutions then a difference of potential will be set up. • This type of equilibrium is known as DONNAN.

38. Effect of electrolytes The instability in colloidal solution is characterised either by coagulation or precipitation. The reasons for instability of colloids are addition and removal of electrolytes, coacervation and sensitization. Addition of electrolytes : In lyophobic colloids trace amount of electrolyte addition is required for providing charge to colloidal particle which overcome the attraction forces between particles. Addition of excess amount of electrolyte leads to coagulation because it provides both the charges. Under this condition, repulsive forces are diminished with dominance of attractive forces and colloids gets coagulated.

39. Cont... In lyophobic colloids accumulation of opposite charge particle changes the zeta potential which leads to coagulation. Removal of electrolytes: Coagulation of colloid is observed when electrolyte is completely removed from the sol. This happen due to repulsive forces. Addition of non-solvent : Addition of less polar solvent like alcohol or acetone causes the dehydration of colloidal particles of lyophilic sols. If electrolyte is added in such situation it leads to precipitation of colloids.

40. Coacervation : When oppositely charged hydrophilic colloids are mixed, a colloidal rich layer separates which is called as Coacervate . This phenomenon in which separation take place on mixing two dispersions on mixing is called Coacervation. E.g Gelatin is positively charged and acacia having negatively charged particle. When two are mixed together ,tw0 layers are formed ,the upper layer of low viscosity having a poor concentration of colloidal material and a lower layer of higher viscosity containing high concentration of colloidal material.

41. Sensitisation : In the presence of very small amount of hydrophilic colloids ,the hydrophobic colloids may become even more susceptible to precitation from electrolyte. i.e Precipitation of hydrophobic colloids by the addition very small amount of electrolyte.

42. Stability studies include chemical and physical stability. 1) Reasons for the instability of dispersion. 2)Suitable measures to stabilise the dispersion. The physical stability can be achieved by maintaining the particles in Brownian motion The way to achieve this property are. 1) P rovide electric charge on the surface of the dispersed particles. The like charges on the particles will prevent these coming closer together and thus maintaining a Brownian movement . This factors plays a significant role in case of lyophobic colloids. 2) Maintain a solvent sheath around the particle. This solvent layer prevents the particle coming closer and also maintain Brownian movement. This factors plays an imp role in case of lyophilic colloids.

43. Stability of colloids : 1) Protection /protective colloids 2) Schulze –hardy rule 3) Gold Number 4) DLVO Theory. 1) Protection /protective colloids: Larger concentration of hydrophilic colloids increase the stability of hydrophobic colloids towards precipitation of electrolytes. The hydrophilic colloids adsorbs on the surface of hydrophobic colloids particles and form a protective layer, Thus preventing them from precipitation on addition of an electrolyte, this phenomenon is called protection.

44. Cont... The hydrophilic solution used for the purpose of protecting the hydrophobic colloid is known as protective colloids. Larger conc. of hydrophilic colloids on hydrophobic colloids Protective layer on surface. Avoid precipitation & this hydrophilic colloids form ... Protective colloid, increase stability of lyophobic colloids.

45. 2) Schulze –Hardy rule Coagulation of colloid by the addition of electrolyte solution which reduce the zeta potential . Lyophilic colloids Addition of large amt. of electrolyte solution Form ppt. Lyophobic colloids Addition of small amt. Electrolyte Schulze –hardy rule: The higher valency of ion, the greater is the precipitating power. E.g. Al 3+ > mg 2+ > Na + higher ppt power

46. 3) Gold Number : It is a measure of the protective ability of hydrophilic colloids. Def : The number of mg of hydrophilic colloids which when added to 10 ml to red gold solution prevents the change in colour from red to violet on the addition of 1 ml of 10 % solution of NaCl . Or The minimum weight in mg of protective colloids which is required to prevent a colour change from red to violet in 10 ml of gold sol on addition of 1 ml of 10 % solution of NaCl . Change in colour Change in particle size Lower the gold number Higher protective ability of colloids.

47. Determination of Gold Number

48. Procedure : Test tube containing 10 ml of gold solution are taken To each test tube protective colloid is added in increasing concentration. Then added 1 ml of 10 % sodium chloride solution. At higher conc. of the protective colloid the gold solution does not change its colour ,while at lower conc. ,the gold solution changes colour from red to violet.

49. 4) DLVO Theory This theory developed to describe stability of lyophobic colloids. DLVO theory is discovered by Derjaguin and Landau Verwey Overbeek describes the stability of lyophobic colloids. Based on two principles: 1) Electrostatic repulsive force. 2) Van der waal force of attraction. According to this theory, the distance between two dispersed particle influences particle- particle interaction. In a colloidal dispersion ,the Brownian motion result in frequent collision between particle. Interactions like attraction and repulsion are responsible for stability of colloids.

50. Cont... When attractive force are dominant, particle adhere after collision and aggregate.. When repulsive force are dominant ,particle rebound and remain dispersed. It is used to determine the amount of electrolyte required to precipitate or stabilise a colloid. A) Van der waal attraction forces: Depend on chemical nature and size of the particle. These are London type forces (temporary attractive force)and potential energy of attraction is represented by V A . B) Electrostatic Repulsive Force: Depend on density ,surface charge and thickness of double layer . Indicate magnitude of zeta potential ,represented by V R.

51. Cont... Net energy of interaction (VT) V T = V A + V R Peptization : For development of stable dispersion of colloids particle in dispersion medium, Generally it is the method of changing a precipitate in to colloidal solution via shaking with dispersion medium in presence of slight qty of electrolyte The electrolytes utilised in this method are known peptizing agent.

52. Cont... The precipitate adsorbs the common ion and electrically charged particles then split from the precipitate as colloidal particle. Normally , Peptization is the reverse of coagulation of solution. E.g ferric hydroxide Fe(OH),produced a solution through adding ferric chloride.