BSPh 2023 Unit 4.1 Colloidal Dispersion PDF

UNIT 4. HETEROGENEOUS SYSTEMS UNIT 4. HETEROGENEOUS SYSTEMS 4.1 Colloidal dispersions 4.1.1 Types of colloidal systems 4.1.2 Properties of colloids 4.1.3 Pharmaceutical applications 4.2 Coarse dispersions 4.2.1 Classification of coarse dispersions 4.2.2 Desirable qualities, pr...

UNIT 4. HETEROGENEOUS SYSTEMS UNIT 4. HETEROGENEOUS SYSTEMS 4.1 Colloidal dispersions 4.1.1 Types of colloidal systems 4.1.2 Properties of colloids 4.1.3 Pharmaceutical applications 4.2 Coarse dispersions 4.2.1 Classification of coarse dispersions 4.2.2 Desirable qualities, properties, and formulation of suspensions and emulsions 4.2.3 Stability and bioavailability of suspensions and emulsions 4.3 Interfacial Phenomena 4.3.1 Measurement of interfacial and surface tension 4.3.2 Application to pharmacy UNIT 4. HETEROGENEOUS SYSTEMS Learning Outcomes Demonstrate knowledge of the different types of colloids and their applications in pharmacy Demonstrate knowledge on the classification and properties of coarse dispersions Demonstrate knowledge on the measurement and application to pharmacy of interfacial phenomena UNIT 4. HETEROGENEOUS SYSTEMS Learning Objectives Distinguish colloidal types and their pharmaceutical relevance ✓ Understand the theory and technology of dispersed systems ✓ Identify the characteristics of colloids ✓ Differentiate the optical, kinetic and electric properties of colloids ✓ Identify the different types of colloid and their application to pharmacy Discuss the classifications, properties and the factors affecting the stability of suspensions and emulsions ✓ Differentiate suspension, emulsion and other pharmaceutical semi-solids ✓ Discuss the physical properties necessary in the preparation of suspension, emulsion, and semisolids ✓ Understand the different theories in emulsification ✓ Discuss the drug kinetics and drug diffusion in a coarse dispersed system Understand interfacial phenomena and describe the methods of measuring interfacial and surface tension ✓ Differentiate interface, interfacial tension, and surface tension ✓ Identify the types of interfaces present in various pharmaceutical dosage forms DISPERSED SYSTEMS Dispersed systems consists of particulate matter (dispersed phase) which is distributed throughout a continuous phase (dispersion medium). These systems are classified according to the mean particle diameter of the dispersed material: Colloidal Coarse Dispersion Dispersion Molecular Dispersion DISPERSED SYSTEMS 1. 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) ▪ Examples: Colloidal silver sols, natural and synthetic polymers.  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 semipermeable membrane. ▪ 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. ▪ Examples: Emulsions, Suspension and RBC’s. 3. Molecular Dispersion (less than 0.01 µm) ▪ The particles of this system are invisible in electron microscope. ▪ They can pass through the filter papers as well as semipermeable membrane. ▪ 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. ▪ Examples: Ordinary ions, Glucose, Urea, Oxygen.  COLLOIDAL DISPERSIONS ▪ The term colloid is derived from two words ‘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. ▪ Gums (acacia, tragacanth), Natural rubbers etc. ▪ Some colloids encountered in pharmacy includes surfactant micelles, suspensions, emulsions, inhalation aerosols etc. SIZES AND SHAPES OF COLLOIDS 1. Size Particles lying in the colloidal size have large surface area when compared with the surface area of an equal volume of larger particles. Specific surface: the surface area per unit weight or volume of material. The possession of large specific surface results in: 1. Additional effect – 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. 2. 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. Example: Red gold sol takes a blue colour when the particles increases in size.  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. 2. Shapes 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 DIFFERENT SHAPES OF COLLOIDS The following properties are affected by changes in the shape of colloidal particles: Flowability Sedimentation Pharmacological action 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 2. Based on the interaction between colloidal phases Lyophilic Lyophobic colloids colloids Association colloids  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.  Lyophilic colloids ▪ 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) ▪ Example: the dissolution of acacia or gelatine in water leads to formation of a solution.  Lyophilic 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. COMPARISON OF LYOPHILIC AND LYOPHOBIC COLLOIDS Lyophilic colloids Lyophobic colloids Colloidal particles have greater affinity for the Colloidal particles have little affinity for the dispersion medium. dispersion medium. Owing to their affinity for the dispersion Material does not disperse spontaneously, and medium, the molecules disperse spontaneously hence lyophobic sols are prepared by to form colloidal solution. dispersion or condensation methods. These colloids form “Reversible sols” These colloids form “Irreversible sols”. Viscosity of the dispersion medium is increased Viscosity of the dispersion medium is not greatly by the presence of colloidal particles. increased by the presence of colloidal particles. Dispersions are stable, generally in the presence Lyophobic dispersions are unstable in the of electrolytes, they may be salted out by high presence of even small concentrations of concentrations of very soluble electrolytes. electrolytes because they already have charges. Dispersed phase consists generally of large Dispersed phase ordinarily consists of inorganic organic molecules such as gelatin, acacia lying particles, such as gold or silver. within colloidal size range.  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 concentration, 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 Concentration (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. ▪ 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 charge on the micelles. ▪ The viscosity of the system increases as the concentration of the amphiphile increases because micelles increase in number and become asymmetric.  OPTICAL PROPERTIES OF COLLOIDS 1. Faraday Tyndall Effect ▪ When a strong beam of light is passed perpendicularly through two solutions, i.e. true solution and colloidal solution, which are placed against a dark background, 1. The path of light beam is not visible in case of true solution. 2. 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. 2. Light Scattering effect This is based on Faraday - Tyndall effect. It is widely used in the determination of size, 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. - Used to study proteins, association colloids and lyophobic sols. - Scattering described in terms of turbidity, T - Turbidity: the fractional decrease in intensity due to scattering as the incident light passes through 1 cm of solution. - Turbidity is proportional to the molecular weight of lyophilic colloid Optical Properties of Colloids Hc / T = 1/M + 2Bc T: turbidity C: conc of solute in gm / cc of solution M: molecular weight B: interaction constant H: constant for a particular system 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). Brownian motion Diffusion Osmotic pressure Sedimentation Viscosity KINETIC PROPERTIES OF COLLOIDAL SYSTEM Brownian motion -The zig-zag movement of colloidal particles continuously and randomly. This brownian motion arises due to the uneven distribution of the collisions between colloid particle and the solvent molecules. - Brownian movement was more rapid for smaller particles. - It decrease with increase the viscosity of the medium. KINETIC PROPERTIES OF COLLOIDS Diffusion - Particles diffuse spontaneously from a region of higher conc. To one of lower conc. Until the conc. of the system is uniform throughout. - Diffusion is a direct result of Brownian motion. - Fick's first law used to describe the diffusion: (The amount of Dq of substance diffusing in time dt across a plane of area A is directly proportional to the change of concentration dc with distance traveled dq = -DA (dc / dx) dt KINETIC PROPERTIES OF COLLOIDS Diffusion D → diffusion coefficient the amount of the material diffused per unit time across a unit area when dc/dx (conc. gradient) is unity. - The measured diffusion coefficient can be used to determine the radius of particles or molecular weight. KINETIC PROPERTIES OF COLLOIDS Osmotic pressure Van 't hoff equation:  = cRT - Can be used to determine the molecular weight of colloid in dilute solution. - Replacing c by C / M (where C = the grams of solute / liter of solution, M = molecular weight) /C = RT/M  = osmotic pressure R = molar gas constant KINETIC PROPERTIES OF COLLOIDS Sedimentation - The velocity of sedimentation is given by Stokes‘ Law: v = d2 (i-e)g/18η V = rate of sedimentation D = diameter of particles  = density of internal phase and external phase g = gravitational constant η = viscosity of medium KINETIC PROPERTIES OF COLLOIDS Viscosity - It is the resistance to flow of system under an applied stress. The more viscous a liquid, the greater the applied force required to make it flow at a particular rate. - The viscosity of colloidal dispersion is affected by the shape of particles of the disperse phase: Sphero colloids dispersions of low viscosity Linear particles more viscous dispersions ELECTRIC PROPERTIES OF COLLOIDS  The particles of a colloidal solution are electrically charged and carry the same type of charge, either negative or positive.  The colloidal particles therefore repel each other and do not cluster together to settle down.  The charge on colloidal particles arises because of the dissociation of the molecular electrolyte on the surface.  E.g. As2S3 has a negative charge During preparation of colloidal As2S3 , H2S is absorbed on the surface and dissociate to H+ (lost to the medium) and S-2 remain on the surface of colloid. ELECTRIC PROPERTIES OF COLLOIDS  Fe(OH)3 is positively charged Due to self dissociation and loss of OH- to the medium,so they become [Fe(OH)3] Fe+3 ELECTRIC PROPERTIES OF COLLOIDS Electrophoresis Electro-osmosis Sedimentation potential Streaming potential Electrophoresis  Electrophoresis is the most known electrokinetic phenomena. It refers to the motion of charged particles related to the fluid under the influence of an applied electric field.  If an electric potential is applied to a colloid, the charged colloidal particles move toward the oppositely charged electrode.  Electro-osmosis  It is the opposite in principal to that of electrophoresis.  When electrodes are placed across a clay mass and a direct current is applied, water in the clay pore space is transported to the cathodically charged electrode by electro-osmosis.  Electro-osmotic transport of water through a clay is a result of diffuse double layer cations in the clay pores being attracted to a negatively charged electrode or cathode. As these cations move toward the cathode, they bring with them water molecules that clump around the cations as a consequence of their dipolar nature.  Sedimentation potential  The sedimentation potential also called the (Donnan effect).  It is the potential induced by the fall of a charged particle under an external force field.  It is analogous to electrophoresis in the sense that a local electric field is induced as a result of its motion.  if a colloidal suspension has a gradient of concentration (such as is produced in sedimentation or centrifugation), then a macroscopic electric field is generated by the charge imbalance appearing at the top and bottom of the sample column. Streaming potential  Differs from electro-osmosis in that the potential is created by forcing a liquid to flow through a bed or plug of particles.  Stabilization serves to prevent colloids STABILITY OF from aggregation. COLLOIDS  The presence and magnitude, or absence of a charge on a colloidal particle is an important factor in the stability of colloids.  Two main mechanisms for colloid stabilization: 1-Steric stabilization i.e. surrounding each particle with a protective solvent sheath which prevent adherence due to Brownian movement 2-electrostatic stabilization i.e. providing the particles with electric charge STABILITY OF COLLOIDS A- Lyophobic sols: - Unstable. - The particles stabilized only by the presence of electrical charges on their surfaces through the addition of small amount of electrolytes. - The like charges produce repulsion which prevent coagulation of the particles and subsequent settling. - Addition of electrolytes beyond necessary for maximum stability results in accumulation of opposite ions and decrease zeta potential results in coagulation and precipitation of colloids. - Coagulation also result from mixing of oppositely charged colloids. STABILITY OF COLLOIDS B- Lyophilic sols and association colloids: - Stable - Present as true solution - Addition of moderate amounts of electrolytes not cause coagulation (opposite lyophobic) ** Salting out: Definition: agglomeration and precipitation of lyophilic colloids. STABILITY OF COLLOIDS  This is obtained by: 1- Addition of large amounts of electrolytes - Anions arranged in a decreasing order of precipitating power: citrate > tartrate > sulfate > acetate > chloride> nitrate > bromide > iodide - The precipitation power is directly related to the hydration of the ion and its ability to separate water molecules from colloidal particles 2- addition of less polar solvent - e.g. alcohol, acetone STABILITY OF COLLOIDS - The addition of less polar solvent renders the solvent mixture unfavourable for the colloids solubility ** Coacervation: The process of mixing negatively and positively charged hydrophilic colloids, and hence the particles separate from the dispersion to form a layer rich in the colloidal aggregates (coacervate) SENSITIZATION AND PROTECTIVE COLLOIDAL ACTION:  Sensitization: the addition of small amount of hydrophilic or hydrophobic colloid to a hydrophobic colloid of opposite charge tend to sensitize (coagulate) the particles.  Polymer flocculants can bridge individual colloidal particles by attractive electrostatic interactions.  For example, negatively-charged colloidal silica particles can be flocculated by the addition of a positively-charged polymer. SENSITIZATION AND PROTECTIVE COLLOIDAL ACTION:  Protection: the addition of large amount of hydrophilic colloid (protective colloid) to a hydrophobic colloid tend to stabilize the system.  This may be due to: The hydrophile is adsorbed as a monomolecular layer on the hydrophobic particles. APPLICATIONS OF COLLOIDAL SOLUTIONS 1- Therapy--- Colloidal system are used as therapeutic agents in different areas. e.g- Silver colloid-germicidal Copper colloid-anticancer Mercury colloid-Antisyphilis 2- Stability---e.g. lyophobic colloids prevent flocculation in suspensions. e.g- Colloidal dispersion of gelatin is used in coating over tablets and granules which upon drying leaves a uniform dry film over them and protect them from adverse conditions of the atmosphere. APPLICATIONS OF COLLOIDAL SOLUTIONS 4- Absorption--- As colloidal dimensions are small enough, they have a huge surface area. Hence, the drug constituted colloidal form is released in large amount. e.g- sulphur colloid gives a large quantity of sulphur and this often leads to sulphur toxicity 5- Targeted Drug Delivery--- Liposomes are of colloidal dimensions and are preferentially taken up by the liver and spleen. APPLICATIONS OF COLLOIDAL SOLUTIONS 6- Photography: A colloidal solution of silver bromide in gelatine is applied on glass plates or celluloid films to form sensitive plates in photography. 7- Clotting of blood: - Blood is a colloidal solution and is negatively charged. - On applying a solution of Fecl3 bleeding stops and blood clotting occurs as Fe+3 ions neutralize the ion charges on the colloidal particles.