COLLEGE OF PHARMACY

1. COLLEGE OF PHARMACY PHARMACEUTICS II (PHT 312) Disperse system & Colloids Dr. Mohammad Javed Ansari, PhD. Contact info: javedpharma@gmail.com

2. Disperse Systems & Colloids

3. objectives of the lecture • At the end of this lecture, you will be aware of: • What are disperse systems? • What are various types of disperse systems? • What are colloidal and coarse dispersions? • What are various colloidal formulations? • What are advantages / disadvantages of colloidal formulation? • What are various properties of colloids? • What are stability problems of colloids? • How colloids are stabilized? • How colloids are prepared?

4. Lecture outlines • Definition of Colloidal dispersion. • Colloids in nature • TYPES OF COLLOIDAL SYSTEMS • Lyophilic colloids • Lyophobic colloids • Amphiphilic or Association Colloids • METHOD OF PREPARATION • Dispersion method (mill, Ultrasonic treatment) • Condensation method: (super-saturation, chemical reaction) • Purification / Separation of colloids. • Dialysis, Electro-dialysis and Ultra filtration • Properties of Colloids (Optical, Kinetic, Electrical, Electro-kinetic). • Stability of Colloid Systems • Application of Colloids

5. Dispersed systems consist of particulate matter known as dispersed phase, dispersed throughout a continuous or dispersion medium. Dispersed systems are classified according to particle size Coarsedispersion > 1 m suspension & emulsion Colloidaldispersion 1 nm – 500 nm colloids Colloidal System is defined as the heterogeneous biphasic system in which dispersed phase is subdivided into nano size range (1-1000 nanometer). Nanoparticles are small colloidal particles, but not all small colloidal particles are nanoparticles.” If all particles in a colloidal system are of (nearly) the same size the system is called monodisperse; in the opposite cases the systems are heterodisperse /polydisperse.

6. Colloidal Systems • It is not necessary for the units of a colloidal system to be discrete (separate particles) • Therefore continuous network structures, the basic units of which are of colloidal dimensions also fall in this class (e.g. porous solids, gels and foams). • Nor it is necessary for all three dimensions to be in the colloidal range. • Films (only one dimension) and fibers (only two dimensions) are in nano range, may also be classified as colloidal. • Eg. Hydrophillic colloids like alginates, agar gelatin, pectin, cellulose derivatives and polymers.

7. Colloidal Systems

8. TYPES OF COLLOIDAL SYSTEMS AND THEIR • METHOD OF PREPARATION • Depending upon the interaction between dispersed colloids and dispersion medium, they are classified as • 1. Lyophilic colloids = solvent loving colloids. • There is an affinity between colloidal particles and dispersion medium. • Spontaneous: Colloids are spontaneously formed by dispersing the material in the solvent e.g. dispersion of acacia or gelatin in water (hydrophilic colloid) or nitrocellulose in alcohol ether (collodion). • Reversible : If solvent is evaporated, the sol can be made again by simply re-mixing with solvent. • Very stable: don’t need any stabilizing agents.

9. TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION • 2. Lyophobic colloids = solvent hating colloids • The colloidal particles have very little affinity, if any, for the dispersion medium. Eg. Metals, their hydroxides and sulphides. • Special technique needed for their preparation. • Unstable: require stabilizing agents. • Irreversible: once precipitated, don’t return. • A- Dispersion method: Coarse particles are reduced in size by the use of colloidal mill or ultrasonics. Colloidal mill: coarse material is sheared in a narrow gap between a static cone and a rapid rotating cone. Ultrasonic treatment: the passage of ultrasonic waves through a dispersion medium.

10. TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION • B- Condensation method: • Sub-colloidal particles are caused to aggregate into colloidal ones. • By super-saturation: high degree of initial super-saturation followed by growth of nuclei (by change of solvent or reduction of temperature). • e.g. addition of water to saturated alcoholic solution of sulfur • By chemical reaction: Reduction, oxidation or hydrolysis • e.g. oxidation of hydrogen sulfide leads to formation of colloidal sulfur

11. TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION 3. Amphiphilic or Association Colloids Amphiphiles or surface active agents are molecules characterized by having a hyrophilic head and a lipophilic tail. When present in a liquid at low concentration the amphiphiles exist separately and are in a subcolloidal size range. When the concentration exceeds a certain level (CMC) the molecules aggregate to form micelles (contain 50 or more monomers). Micelles lie within the colloidal size range.

12. Purification / Separation of colloids Dialysis Colloidal particles are not retained by conventional filter papers but are too large to diffuse through the pores of semipermeable (dialysis) membranes of collodion or cellophane. The pore size will permit only the passage of smaller particles (molecular range). This process is known as dialysis. The colloidal material is retained while the subcolloidal material is distributed equally in both compartments. By continually removing the liquid in the acceptor cell it is possible to obtain colloidal material free from subcolloidal contaminants

13. Purification / Separation of colloids Electro-dialysis An electrical potential may be used to increase the rate of movement of ionic impurities through a dialysis membrane. Ultrafiltration By applying pressure or suction the solvent and molecular particles are forced across the membrane but the larger particles are retained. Pharmaceutical application of dialysis Haemodialysis: Small molecular weight impurities from the body (blood) are removed by passage through a membrane.

14. Properties of Colloids • Due to their small size they do not settle out of solution. • Particles lying in the colloidal size range possess an enormous surface area compared with the surface area of an equal volume of larger particles. • In order to compare surface area of different systems we use the term specificsurfacearea (= surface area per unit weight or volume of material). • Large specific surface area results in many uniqueproperties of colloidal dispersions. • Optical properties of colloids. eg.Tyndall (Faraday) Effect • Kinetic properties of colloids eg.Brownian motion, diffusion, osmosis, viscosity etc. • Electrical Properties of Colloids eg. Zeta potential • Electro-kinetic Properties of Colloids eg. Electrophoresis

15. Properties of Colloids • Light scattering / Tyndall (Faraday) Effect • When a strong beam of light is passed through a colloidal sol some of the light may be absorbed, some is scattered and the remainder is transmitted undisturbed through the sample. • Because of the scattered light the sol appears turbid: This is known as the Tyndall effect. • Light scattering measurements are of great value for estimating particle size and shape and number of particles per unit weight or volume. Optical properties of colloids

16. Optical properties of colloids

17. Optical properties of colloids • Antimony and arsenic trisulfide change from red to yellow as the particle size is reduced from coarse to colloidal size. • GOLD CHLORIDE HAS A DEEP RED COLOR, SILVER IODIDE IS YELLOW. • EVALUATION OF COLLOIDS • Ultra-microscope: Allows the examination of the light spots responsible for the Tyndall cone. • The light spots corresponding to the particles are counted and average particle size may be calculated. • ElectronMicroscope: It is capable of taking pictures of the actual particles even those approaching molecular dimensions. • It is used to observe size, shape and structure of colloidal particles.

18. Properties which are related to the motion of particles with respect to the dispersion medium 1. Brownian motion 2. Diffusion Particles spontaneously diffuse from a region of higher concentration to a region of lower concentration until the concentration of the system is uniform throughout. Diffusion is a direct result of Brownian movement. Kinetic properties of colloids Random movement of the colloidal particles. The erratic motion is due to the random collision (accident) of the colloidal particles with the molecules of the dispersion medium. The velocity of the particles increase with decreasing particle size.

19. The rate of diffusion is expressed by Fick's first law, = - DA dmthe amount of substance diffusing in time dt across a plane of area A is directly proportional to concentration gradient dc/dx (the change of concentration dc with distance traveled dx). D is known as the diffusion coefficient (area per unit time). The negative sign is because diffusion occurs in the direction of decreasing concentration. dm dt dc dx

20. RT 6   r N Kinetic properties of colloids…. Diffusion coefficient obtained from Fick's law can be used to obtain the radius of approximately spherical colloidal particles D = Diffusion coefficient obtained from Fick's law R = Molar gas constant T = Absolute temperature  = Viscosity of the solvent r = radius of the spherical particle N = Avogadro's number The diffusion coefficient may be also used to obtain the molecular weight of approximately spherical molecules, such as egg albumin and hemoglobin. D =

21.  C RT M = + B C Kinetic properties of colloids…. 3. Osmotic Pressure: If a solution and a solvent are separated by a semipermeable membrane the tendency to equalize concentration on either side of the membrane results in a net diffusion of solvent across the membrane. The pressure necessary to balance the osmotic flow is called the osmotic pressure. Osmotic pressure can be used to determine the molecular weight using the following equation (derived from Van’t Hoff equation) C = Concentration of solution T = Absolute temperature M = Molecular weightR= Gas constant B = Constant depending on the degree of interaction between dispersed phase and dispersion medium

22. Kinetic properties of colloids…. 4. Sedimentation The velocity v of sedimentation of spherical particles is given by Stoke's law v = d = diameter of the particles o = density of the medium = density of the spherical colloidal particles. g = acceleration due to gravity.  = viscosity of the medium If the particles are only subjected to the force of gravity, then the lower size limit of particles obeying Stoke's equation is about 0.5 m. d2 ( - o) g 18  This is because Brownian movement ends to counteract sedimentation due to gravity and promotes mixing.

23. Kinetic properties of colloids…. • 5. Viscosity • Viscosity is an expression of the resistance to flow of a 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 present section is concerned with: • the flow properties of dilute colloidal systems • the manner in which viscosity data can be used to obtain the molecular weight of the disperse phase. • Viscosity studies also provide information regarding the shape of the particles in solution.

24. Einstein developed an equation of flow applicable to dilute colloidal dispersions of spherical particles: •  = o (1 + 2.5 ) • o = viscosity of the dispersion medium • = viscosity of the dispersion medium when the volume fraction of colloidal particles is  • The volume fraction  is defined as the volume of the particles divided by the total volume of the dispersion. • Several viscosity coefficients may be defined with respect to this equation: • relative viscosity (rel) • specific viscosity (sp) • intrinsic viscosity (int) 5. Viscosity: Kinetic properties of colloids….

25. 5. Viscosity: Kinetic properties of colloids…. Relative viscosity: rel = /o = 1 + 2.5  Specific viscosity: sp= - o /o = rel -1= 2.5  Since volume fraction is directly related to concentration sp /C= K C = Concentration expressed in grams of colloidal particles per 100 ml of total dispersion. If sp/C is plotted against C and the line is extrapolated to infinite dilution, the intercept is known as the intrinsic viscosity int

26. Electrical Properties of Colloids These are properties, which depend on, or are affected by the presence of a charge on the surface of a particle. Particles dispersed in Liquid media may become charged mainly due to: [1] The surface active adsorption of a particular ionic species present in solution. This may be an ion added to the solution or, in the case of pure water, it may be the hydronium or hydroxyl ion. [2] The charges on particles, which arise from ionization of groups (such as COOH) which may be situated at the surface of the particle. In these cases, the total charge is a function of pH.

27. Electrical Properties of Colloids • The charge carried by colloid protein molecules • will depend on the pH of the dispersion medium. • In alkaline solution: • The carboxylic acid groups of the protein molecules will exist as carboxylate anions. • NH2 --- R ---COO- • (b)In acid solution: • The amino groups of the molecules will be protonated: NH3+ ---R --- COOH • At, alternative pH, known as the isoelectric • point, the protein exist as zwitterion, which is • electrically neutral, both groups are ionized. • The solubility of the protein is at a minimum at • its isoelectric point and therefore precipitation is • facilitated at this pH. NH3+ --- R --- COO-

28. Electrical Properties of Colloids… [3] The charge on a particle surface may be arised when there is a difference in dielectric constant between the particle and its dispersion medium. There will be a transfer of electrons- or ions from the substances of high dielectric constant to those of lower one. As a result when a particle possesses a higher dielectric constant than its dispersion medium, it will acquire a positive charge and vice-versa.

29. Electro-kinetic phenomena The movement of a charged colloidal particles with respect to adjacent liquid phase is the principle of the electro-kinetic phenomena (electrophoresis). Electrophoresis Involves the movement of a charged particle through a liquid under the influence of an applied potential difference. An electrophoresis cell, fitted with two electrodes, contains the dispersion. When a potential is applied across the electrodes, the Electronegative colloid particles migrate to the oppositely charged electrode.

30. Stability of Colloid Systems • The presence and magnitude, or absence of a charge on a colloidal particle is an important factor in the stability of colloidal systems. • Lyophilic and association colloids are thermodynamically stable. • The addition of an electrolyte to a lyophilic colloid in moderate amounts does not result in coagulation. • A lyophobic sol is thermodynamically unstable. • The particles in such system are stabilized only by the presence of electrical charges on their surfaces. • Stability is accomplished essentially by 2 means: • providing the dispersed particles with an electric charge • surrounding each particle with a protective solvent sheath which prevents mutual adherence when the particles bump as a result of Brownian movement.

31. Stability of Colloid Systems The stability of hydrophobic colloids depends on the zeta potential: when the absolute value of zeta potential is above 50 mV the dispersions are very stable due to mutual electrostatic repulsion. when the zeta potential is close to zero the coagulation (formation of larger assemblies of particles) is very fast and this causes a fast sedimentation. Therefore, the addition of a small amount of electrolyte to a lyophobic sol tends to stabilize the system by imparting a charge to the particles.

32. Application of Colloids • Colloids are extensively used for modifying the properties of pharmaceutical agents. • Colloidal drugs exhibit substantially different properties when compared with traditional forms of the dosage forms. • The most common property that is affected is the solubility of a drug. • Another important pharmaceutical application of colloids is their use as drug delivery systems. • The most often used colloid- type delivery systems include hydrogels, microspheres, liposomes, micelles, nanoparticles, and nanocrystals.

33. Application of Colloids • Hydrogels can be defined as cross-linked or interwoven polymeric networks, which absorb and retain large amounts of water. • Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards. • Hydrophilic and biocompatible microgels could provide a unique mode for targeted delivery of encapsulated drugs via blood. • Environment sensitive hydrogels have the ability to sense changes in the pH, temperature, or the concentration of a specific metabolite and release their load as a result of such a change; these hydrogels can be used as site specific controlled drug delivery systems

34. Application of Colloids • Microparticles refers to a particle with a diameter of 1–1000 μm, irrespective of the precise interior or exterior structure. • Microparticles, may be classified as “microspheres” specifically refers to spherical microparticles and • the “microcapsules” which have a core surrounded by a material which is distinctly different from that of the core. The core may be solid, liquid, or even gas. • Nanocapsules are sub-microscopic colloidal carrier systems composed of an oily or an aqueous core surrounded by a thin polymer membrane

35. Application of Colloids • Microemulsions are excellent candidates as potential drug delivery systems because of their improved drug solubilization, long shelf life, and ease of preparation and administration. • In contrast to Microparticles, which demonstrate distinct differences between the outer shell and core, microemulsions are usually formed with more or less homogeneous particles. • Three distinct Microemulsions- oil external, water external, and middle phase- can be used for drug delivery, depending upon the type of the dug and the site of action. • Nanoemulsions consist in very fine oil-in-water dispersions, having droplets diameter smaller than 100 nm.

36. Application of Colloids

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