Colloids - Physical Pharmacy

Colloids - Physical Pharmacy

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  1 COLLOIDS
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  2 Introduction  Thomas Graham(1861) studied the ability of dissolved substances to diffuse into water across a permeable membrane.  He observed that crystalline substances such as sugar, urea, and sodium chloride passed through the membrane, while others like glue, gelatin and gum did not.  The former he called crystalloids  And the latter colloids (Greek, kolla = glue ; eidos = like).
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  3 Introduction  Graham thoughtthat the difference in the behavior of ‘crystalloids’ and ‘colloids’ was due to the particle size.  Later it was realized that any substance, regardless of its nature, could be converted into a colloid by  subdividing it into particles of colloidal size.
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  4 Introduction  Dispersed system–A system in which one phase (dispersed phase) is distributed uniformly as particles throughout another phase (dispersion medium)  Dispersed system can also be classified on basis of the size of dispersed phase as  Molecular dispersion  Colloidal dispersion  Coarse dispersion
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  5 comparison of varioustypes of dispersions
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  6 Introduction  The colloidalsolutions or colloidal dispersions are intermediate between  true solutions size less than 10 Å or 1nm and suspensions size more than 2000 Å or 0.5µm.  In other words, the diameter of the dispersed particles in a colloidal dispersion is more than that of the solute particles in a true solution and smaller than that of a suspension.
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  7 Introduction  When thediameter of the particles of a substance dispersed in a solvent ranges from about 10Å to 2,000Å, the system is termed a colloidal solution, colloidal dispersion, or simply a colloid.  The material with particle size in the colloidal range is said to be in the colloidal state.
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  8 Particle size (indicatedby diameter) range of true solution, colloidal dispersion, and suspension. True solution 1Ao Colloidal solution 10Ao Suspension 2000Ao
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  9 Pharmaceutical application of colloids As a therapeutic agent-colloidal Cu in cancer  Used as a diagnostic agent –colloidal gold for paresis  As a additives- polymers used in P'ceutical preparation  Bindings of drugs - protein  As a plasma substitutes - dextran as plasma expander  As a coating materials tablet & capsule coated with protect drug  Antibiotics –penicillin injection  Foods  Solubilization -surfactant  Bioavailability –increase therapeutic activity  Emulsion formation –emulgent colloidal in nature  Gels
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  10 colloidal systems  Forexample, for a colloidal solution of copper in water, copper particles constitute the dispersed phase and water the dispersion medium. Dispersed phase (copper) Dispersion medium (water) Cu Cu Cu Cu Cu
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  11 Types of colloidalsystems  As stated above, a colloidal system is made of a dispersed phase and the dispersion medium.  Because either the dispersed phase or the dispersion medium can be a gas, liquid or solid, there are eight types of colloidal systems possible.  A colloidal dispersion of one gas in another is not possible since the two gases would give a homogeneous molecular mixture.
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  12 Classification Based onthe State of the Dispersed Phase and Dispersion Medium Dispersed Phase Dispersion medium Type Name Examples Gas Liquid foam shaving cream Gas Solid Solid foam froth cork, pumice, foam rubber Liquid Gas Liquid aerosol mist, clouds, fog Liquid Liquid Emulsion milk, hair cream liquid Solid Solid emulsion butter, cheese Solid Gas solid aerosol dust, smoke Solid Liquid Sols ,gel paint, ink, jelly solid solid Solid sol pearls
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  13 Classification Based onthe Nature of Interaction Between Dispersed Phase and Dispersion Medium colloids Lyophilic colloids Lyophobic colloids Association colloids
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  14 Lyophilic colloids  Itsalso called as homogeneous colloids or reversible sols  The dispersed phase of a colloidal dispersion may be classified as Lyophilic (solvent loving)  If the solvent is water so termed as Hydrophilic  Strong affinity of colloidal particles for the dispersion medium (solvent)  Hydrated colloids swell increasing viscosity of the system & Prepared by simply dissolving the material in the solvent  Examples : acacia , methylcellulose, gelatin and albumin
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  15 Lyophobic colloids  Thedispersed phase of a colloidal dispersion may be classified as Lyophobic (solvent hating)  If the solvent is water so termed as Hydrophobic  Little affinity to the dispersion medium.  No change in system viscosity.  Special method for preparation e.g.:  Condensation method  Dispersion method.  Examples : gold, silver, Sulphur
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  16 Method of preparationof Lyophobic colloids  Special method is required to prepare colloids because of the weaker attraction between particles & the medium. 1. Dispersion methods  The general principle involves mechanical dispersion, i.e., converting coarse particles are reduced in size 2. Condensation methods  Materials of subcolloidal dimensions are caused to aggregate into particles within the colloidal size range
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  17 Association colloids  Itsalso called as Amphiphilic colloids and micelles  Certain molecules or ions termed as amphiphiles or surface active agents  These possess polar & non-polar group (water loving & water hating (mixture of both)
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  18 Association colloids cont’d When surfactant present in liquid at low concentration exist separately as monomers & are of subcolloidal size  As the concentration of surfactant increases ,aggregation occurs, the aggregates may contain 50 or more monomers called as micelles  The diameter of micelles is of the order of 50Ao  The concentration at which micelles form is termed as Critical Micelle Concentration (CMC)  CMC is a concentration range and has unit of concentration such as w/w, w/v per cent, moles/ litre, moles/1000 g of solvent etc.
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  22 Classification of Association colloids TypeCompound Amphiphiles Gegenio ns Anionic Sodium lauryl sulphate CH3(CH2) 11 OSO3 - Na+ Cationic Cetyl tri methyl ammonium bromide CH3 (CH2)15N+(CH3) 3 Br- Nonionic Polyoxyethylene lauryl ether CH3(CH2) 10CH20(CH20CH2) 23H - Ampholytic (zwitterionic) Dimethyldodecyl ammoniopropane sulfonate CH3(CH2) 11N+(CH2) 3(CH2) 3OSO2 - -
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  23 Krafft Point, Kt The solubility of a surface active agent depends on the temperature of the system.  But adequate concentration of surface active agent is required to form micelles. This relationship is stated by Krafft point.  Krafft point is defined as the temperature at which the solubility of the surfactant is equal to the CMC
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  24 Properties of differenttypes of colloidal dispersion systems Property Lyophilic Colloids Lyophobic Colloids Association Colloids Dispersed phase mostly organic molecules largely inorganic particles aggregation of surface active agents Nature of interaction stronger, solvent sheath around particle little interaction aggregates are solvated presence of charge less charged, but solvated highly charged charged micelles. but solvated Method of preparation readily form sol special methods are required readily form when conc. ,is equal to CMC Viscosity of the dispersion Higher than that of medium alone Nearly same as the dispersion medium Viscosity increases, but not appreciably Presence of electrolytes low concentrations high concentrations Stable Coacervation ppt Unstable stable Stable precipitates Reversibility reversible irreversible reversible
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  26 Properties of colloids 1.Optical properties of colloids  The Faraday- Tyndall effect  Electron microscope  Light scattering 2. Kinetic properties of colloids  Brownian motion  Diffusion  Osmotic pressure  Sedimentation  Viscosity 3. Electrical properties of colloids  Electrokinetic phenomena
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  27 Optical Properties ofcolloids The Faraday- Tyndall effect  Beam of light directed colloidal sol some of the light may be absorbed, some is scattered and remainder transmitted through the sample.  visible cone due to the light scattered by the colloidal particles. This phenomenon is known as Faraday- Tyndall effect
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  28 Optical Properties ofcolloids Electron Microscope  The use of the ultra-microscope has declined in recent years because it frequently does not resolve lyophilic colloids.  The electron microscope, capable of  Yielding pictures of the actual particles, Even those approaching molecular dimensions  It is now widely used to observe the size, shape, and structure of colloidal particles.
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  29 Optical Properties ofcolloids Electron Microscope  The success of the electron microscope is due to its high resolving power  The radiation source of the electron microscope is a beam of high-energy electrons having wavelengths in the region of 0.01 nm (0.1 Ao).
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  30 Optical Properties ofcolloids Light scattering  This property depends on the Faraday-Tyndall effect  It is a widely used for determining the molecular weight of colloids.  It can also be used to obtain information on the shape and size of these particles.  Scattering can be described in terms of the turbidity  The fractional decrease in intensity due to scattering as the incident light passes through 1 cm of solution. 
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  31 Optical Properties ofcolloids Light scattering  It can be expressed as the intensity of light scattered (Is), in all directions, divided by the intensity of the incident light (I)  At a given concentration of dispersed phase, the turbidity is proportional to the molecular weight of the lyophilic colloid.  Because of the low turbidity of most lyophilic colloids, it is more convenient to measure the scattered light rather than the transmitted light.
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  32 Optical Properties ofcolloids Light scattering  The turbidity can be calculated from the intensity of the scattered light  Its provided that the dimensions of the particle are small compared with the wavelength of the light used.  The molecular weight of the colloid can be obtained from the following equation: c c     2 1 
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  33 Optical Properties ofcolloids Light scattering Where = turbidity in cm-1 c = concentration of solute in g / cm3 M = average molecular weight in g/mole or Dalton B = interaction constant H = constant for particular system c c     2 1  
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  36 Kinetic Properties ofcolloids Brownian motion  The random movement of colloidal particles in the microscopic field  Robert Brown (1827) studied this phenomenon.  The erratic (unpredicted) motion, which may be observed with particles as large as about 5µm  The velocity of the particles increases with decreasing particle size.  Increasing viscosity of medium (by addition of glycerin) ,decreasing or stops the Brownian movement
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  37 Kinetic Properties ofcolloids Diffusion  Particles diffuse spontaneously from a higher region concentration to one of lower concentration until the concentration of the system is uniform throughout.  Diffusion is a direct result of Brownian movement.  Diffusion can be expressed by Fick's first law  the amount dq of substance diffusing in time dt , across a plane of area S is directly proportional to the change of concentration, dc, with distance travelled, dx.
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  38 Kinetic Properties ofcolloids Diffusion  Where, D = diffusion coefficient & has the dimensions of area per unit time.  Dc/dx = concentration gradients. dt dx dc DSdq 
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  39 Kinetic Properties ofcolloids Diffusion  Another method involves  If the colloidal particles can be assumed to be approximately spherical, the following equation can be used to obtain the radius of the particle and the particle weight or molecular weight: OR r kT D 6    r RT D 6
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  40 Kinetic Properties ofcolloids 3 3 4 6        RT D From known diffusion coefficient (D) ,molecular weight of approximately spherical molecules can be obtained Examples – egg albumin, hemoglobin Where , M = molecular weight ν = specific volume in cm3 of 1 gm of solute, obtained from density
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  41 Kinetic Properties ofcolloids Diffusion From above equation following rules of diffusion 1. The velocity of molecules increases with decreasing particle size 2. The velocity of molecules increases with increasing temperature 3. The velocity of molecules decreases with increasing viscosity of the medium
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  42 Kinetic Properties ofcolloids Osmotic pressure  It is mostly useful to measurement of molecular weight range of about 104 to 106  The Van’t Hoff equation for dilute solution  C = molar concentration of solute  This equation can be used to calculate molecular weight of colloids in dilute solution.  Replacing C with Cg/M in above equation Cg = grams of solute/lit of sol OR cRT RT M Cg  M RT Cg  
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  43 Kinetic Properties ofcolloids Osmotic pressure  The quantity for a polymer having a molecular weight of 50,000 is often a liner function of concentration Cg & following equation can be written  B = constant for any particular solvent/solute system gC         g g BC M RT C 1
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  44 Kinetic Properties ofcolloids Sedimentation  The velocity ,v,of sedimentation of spherical particle having a density ρ in a medium of density ρo& a viscosity ηo is given by stoke’s law  If the particles are must be greater than 0.5 µm ,Brownian movement becomes important & tends to offset sedimentation due to gravity & keep the particles mixed instead of settling   o gr v o   9 2 2  
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  45 Kinetic Properties ofcolloids Sedimentation  Stoke’s law applicable-particles spherical & dispersion is dilute.  Colloidal particles beings extremely small, sedimentation due to force of gravity is extremely slow, so value of v would be not measurable.  This can be accomplished by high speed centrifuge or ultracentrifuge  In a centrifuge, g is replaced by x2    o o xr v   9 2 22  
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  46 Kinetic Properties ofcolloids Sedimentation  The instantaneous velocity, v = dx/dt, of a particle in a unit centrifugal field is expressed in terms of the Svedberg sedimentation coefficient s,  Owing to the centrifugal force, particles having a high molecular weight pass from position x1 at time t1 to position x2 at time t2 xw dtdx s 2 / 
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  47 Kinetic Properties ofcolloids Sedimentation  And the sedimentation coefficient is obtained by integrating equation  The distances x1 to x2 and refer to positions of the boundary between the solvent and the high-molecular-weight component in the centrifuge cell.  The boundary is located by the change of refractive index, which can be attained at any time during the run and translated into a peak on a photographic plate. )( )/ln( 12 2 12 ttw xx s  
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  48 Kinetic Properties ofcolloids Sedimentation  The sedimentation coefficient, s, can be computed from last equation after the two distances x1 & x2 are measured on the schlieren photographs obtained at times t1 and t2 and the angular velocity w is equal to 2Π times the speed of the rotor in revolutions per second.  Knowing s and obtaining D from diffusion data, it is possible to determine the molecular weight of a polymer, such as a protein, by use of the expression )1( O S D RT  
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  49 Kinetic Properties ofcolloids Viscosity  The viscosity of a colloidal dispersion is affected by a variety of factors.  Shape of the dispersed particles : Spherical particles impart relatively low viscosity to dispersion, while particles of linear shape yield more viscous systems.  Affinity of particles to the medium : If linear particles are placed in a medium having low affinity for particles, these tend to assume spherical shape and the viscosity falls.
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  50 Kinetic Properties ofcolloids Viscosity  Type of colloids : In general, lyophilic colloids have viscosities manyfold greater than that of the dispersion medium. Lyophobic colloids have viscosities almost equal to the dispersion medium.  Molecular weight of the particles : Higher the molecular weight of the material, greater will be the viscosity. Therefore, by measuring the viscosity, molecular weight of the polymers can be determined, examples: Dextran (plasma expanders), gelatin etc.
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  51 Kinetic Properties ofcolloids Viscosity  Viscosity is an expression of the resistance to flow of a system under an applied stress.  The flow of a dilute colloidal system (having spherical particles) is expressed by an equation developed by Einstein. η =η0(1+2.5Φ) η0 = viscosity of dispersion medium η = viscosity of dispersion Φ = volume fraction of particle
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  52 Kinetic Properties ofcolloids Viscosity  Rearranging equation (7) gives η / η0 = 1+2.5Φ = ηrel i,e relative viscosity η / η0 = 1+2.5Φ = ηsp i.e., specific viscosity ηsp / Φ = 2.5  The volume fraction is estimated as the volume of particles/total volume of dispersion.  The volume fraction Φ, represents the concentration term since Φ is related to c. ηsp / c = 2.5 or k where, c = particles in grams per 100ml of dispersion k = intrinsic viscosity
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  53 Kinetic Properties ofcolloids Viscosity  By determining the η0 and ηrel , ηspe can be estimated.  When ηspc /c is plotted against c, a straight line may be obtained.  Extrapolating this line to infinite dilution (y axis) gives the intercept, which is k value.  This constant, k, is the intrinsic viscosity [η]  The approximate molecular weight of the dispersed phase can be estimated using intrinsic viscosity.  According to Mark- Hownink equation [η] =KMa
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  54 Kinetic Properties ofcolloids Viscosity  Constants K and a are characteristics of a particular polymer- solvent system.  These constants are obtained by calibrating with a colloidal dispersion of known characteristics and molecular weight (M). ηspe / c concentration
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  55 Electrical Properties ofcolloids Surface charge zeta potential  In general, dispersed particles possess a charge on their surfaces.  The distribution of ions in the environment of a charged particle is explained by the concept of the electrical double layer.  When particles move, this shell of the double layer also moves along with the particle.  The electrical potential in the plane of shear of the charged particle is called zeta potential.
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  56 Electrical Properties ofcolloids Surface charge zeta potential  Zeta potential has an application in predicting the stability of the dispersion system.  Zeta potential can be determined using the method of electrophoresis. ELECTROPHORESIS  The principle of electrophoresis is used to determine the sign and magnitude of zeta potential.  It involves the movement of a charged particle through a liquid under the influence of an applied potential difference.
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  57 Electrical Properties ofcolloids ELECTROPHORESIS  The design of an electrophoresis cell is given in Figure
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  58 Electrical Properties ofcolloids ELECTROPHORESIS  An electrophoresis cell is fitted with two electrodes & the dispersion is introduced into the cell.  When a potential is applied across the electrodes, particles migrate towards oppositely charged electrodes.  If the particles move towards anode, the charge on the particle is negative.  If particles move towards cathode, the charge on the particles is positive.  Thus the sign of zeta potential can be determined.
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  59 Electrical Properties ofcolloids ELECTROPHORESIS  The rate of migration is a function of the charge on a particle  The ultra microscope is used to observe the migration of particles.  Since shear plane of the particle is located at the periphery of the tightly bound layer, the potential estimated represents the zeta potential.  Thus, sign and magnitude of the migration rate can be determined.
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  60 Electrical Properties ofcolloids ELECTROPHORESIS  The apparatus is standardised by the use of particles of known potential.  As the potential gradient across the electrodes increases, the velocity of migration of a particle increases.  Velocity of migration of particles, cm/sec proportional to potential gradient across the particles, volts or  Proportionality Constant ξ represents zeta potential Ev      
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  61 Electrical Properties ofcolloids ELECTROPHORESIS  proportionality constant ξ represents zeta potential.  There are a number of other factors that influence the migration.  Therefore, the zeta potential of a colloidal system may be determined by equation  where ε= dielectric constant of the medium η = viscosity of the medium, poise    4  E v
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  62 Electrical Properties ofcolloids ELECTROPHORESIS  For a colloidal system in which dispersion medium is water, above equation reduces approximately to  The coefficient, 150, at 20°C becomes 128 at 25°C. Thus the magnitude of zeta potential can be determined. Ev /150
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  63 STABILITY OF COLLOIDS Stable colloidal system is one which the particles resist flocculation or aggregation and exhibits a long shelf life.  This will depend on the balance of repulsive & attractive forces that exist between particle as they approach one another.  If all particles have mutual repulsion then the dispersion will remain stable.
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  64 STABILITY OF COLLOIDS Muchdenser form
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  65 STABILITY OF COLLOIDS In 1940's Derjaguin, Verway, Landau and Overbeek developed a theory which dealt with colloidal stability (DLVO).  To maintain colloidal stability, the repulsive forces between particles must be dominant.  Two fundamental mechanisms for repulsive forces are : (1) STERIC REPULSION (2) ELECTROSTATIC (CHARGE) REPULSION
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  66 DLVO THEORY  Accordingto this theory, the distance between "two dispersed particles mainly influences particle-particle interactions.  Using this theory, determine the amount of electrolytes of a particular valency type required to precipitate or stabilized a colloid  In a colloidal dispersion, the Brownian motion results in frequent collisions between particles.  Such interactions are mainly responsible for the stability of colloids. There are two types of interactions, namely attractions and repulsions.
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  67 DLVO THEORY  Whenattractions predominate, the particles adhere after collision and aggregate.  When repulsions predominate, the particles rebound after collisions & remain individually dispersed.  The potential energy versus interparticle distance for particles in a dispersion
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  68 DLVO THEORY The interactionsbetween particles are described as follows:— Van der Waals attraction forces :  These forces depend mainly on the chemical nature and size of the particle.  The Van-der-Waals energy of attraction is represented by VA  VA is decreases as interparticulate distance increases
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  69 DLVO THEORY The interactionsbetween particles are described as follows:— Electrostatic repulsive forces :  The electrostatic repulsive forces depend mainly on the density, surface charge and thickness of the double layer.  These indicate the magnitude of zeta potential.  The Electrostatic repulsive energy VR which decreases exponentially with distance.
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  70 DLVO THEORY The interactionsbetween particles are described as follows:— Net energy of interaction :  An algebraic addition of the above two curves gives the net energy of interaction.  The potential energy is represented by VT
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  71 DLVO THEORY  Atlow electrolyte concentration ,the repulsive forces predominate so that the particles experience only a repulsive force upon approach  The particle remain individual & system is called dispersed or peptized  At a higher concentration of electrolyte, the electrical double layer forces are greatly diminished  As result, Vander – waals forces of attraction predominate & particles encounters net attractive forces ending in coagulation.
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  72 DLVO THEORY Colloidal stabilityrequires a repulsion force:
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  73 Stearic stabilization  Itsinvolves polymers added to the system adsorbing onto the particles surface causing repulsion. Electrostatic stabilization  This is the effect on particle interaction due to the distribution of charged species in the system.  Stabilization or flocculation of a system may be modified simply by altering the concentration of ions in a system. It is reversible process and inexpensive.  Zeta potential is a very good index of the magnitude of the interaction between colloidal particles & measurements are used to assess the stability of colloidal systems.
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  74 Zeta potential  TheZeta potential is the over-all charge a particle acquires in a specific medium.  The magnitude of the Zeta potential gives an indication of the Potential of the colloidal system  If all the particles have a large Positive or Negative Zeta Potential they will repel each other & there is the dispersion stability  If the particles have low Zeta potential then there is no force to prevent the particles coming together and dispersion instability.
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  75 Zeta potential  Aline of demarkation between stable and unstable aqueous dispersions is generally taken at either + 30 or - 30 mV.  Particles with Zeta potentials more positive than + 30 mV are normally considered stable.  Particles with Zeta potentials more negative than - 30 mV are normally considered stable.
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  76 SCHULZE-HARDY RULE (Hofmeister orlyotropic series)  Lyophilic & association colloids are thermodynamically stable & exist in the true solution.  They don’t coagulate on addition of moderate amounts of electrolytes  But they coagulate if sufficient amount of electrolyte is added as was evident with Lyophobic colloids, called salting out  Hardy – Schulze rule arranges ions in the order of their capacity to coagulate hydrophobic colloids, the Hofmeister or Lyotropic series ranks cations & anions in order of coagulation of hydrophilic solution
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  77 SCHULZE-HARDY RULE (Hofmeister orlyotropic series)  Anions of Hofmeister series in decreasing order of precipitating power are  Citrate > Tartrate > Sulphate > Acetate > Chloride  It is depends upon the ability to dislodge solvent sheath from the colloidal particles  When negative & positively charged hydrophilic colloids are mixed, the particles may separate from the dispersion to form a layer rich in the colloidal aggregates  The colloid rich layer is known as a coacervate & the process is called as coacervation  Eg gelatin & acacia
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  78 Sensitization & protectivecolloidal action  In the presence of very small amount of hydrophilic colloids or hydrophobic colloids of opposite charge ,hydrophobic colloids may become more susceptible to precipitation from electrolytes. It is known as Sensitization  When a large amount of hydrophilic colloid particles are added to hydrophobic colloids, these get adsorbed on the hydrophobic particles and form a protective layer around it. This adsorption layer prevents the precipitating ions reaching the sol particle  The colloid that helps to stabilize other colloids is called as a protective colloid.
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  79 Gold number: •The protectiveproperty of colloid is expressed by its gold number •It is defined as the minimum weight in milligrams of a protective colloid (dry weight of dispersed phase) 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 sodium chloride. Protective colloids Gold number / mg Gelatin 0.005-0.01 Albumin 0.08-0.10 Gum acacia 0.10-0.15 Dextrin 6.0-20.0 Potato starch 25
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