Unit I COLLOIDAL DISPERSION

R. VIJAYAKUMAR., M Pharm,
Research Scholar
department of Pharmaceutical Technology.
Anna university- BIT
Tiruchirappalli

B Pharm / 2nd Year ,III Semester.
UNIT-I / Colloidal dispersion's

1. COLLOIDAL DISPERSIONS R.VIJAYAKUMAR ,M Pharm., Assistant Professor, Department of Pharmaceutics, Velallar College of Pharmacy, Erode -12. 1 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

2. Colloidal system is dispersion where in internal phase dispersed particles are distributed uniformly in a dispersion medium (External/continuous Phase). Particle size-0.5 to 1 micron In colloidal systems particles pass through filter paper but do not pass through semi permeable membrane diffuse very slowly. Example: Gelatin Acacia and Rubber Colloids The term colloid means glue like substances 2 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

3. Colloidal systems encountered in pharmacy : Surfactant Micelles Suspensions (may Be > 1 mm) Emulsions (may Be > 1 mm) Inhalation Aerosols Suspensions Of Microorganisms CLASSIFICATION OF COLLOIDAL SYSTEMS ACCORDING TO PARTICLE SIZE Molecular dispersion Colloidal dispersion Coarse dispersion 3 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

4. Therapy --- Colloidal system are used as therapeutic agents in different areas. e.g - Silver colloid-germicidal Copper colloid-anticancer Mercury colloid- Antisyphilis 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 colloids 4 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

5. Absorption --- As colloidal dimensions are small enough, they have a huge surface area. Hence, the drug constituted colloidal form is released in large amount. Targeted Drug Delivery- -- Liposomes are of colloidal dimensions and are preferentially taken up by the liver and spleen. 5 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

6. Dispersed systems consist of particulate matter (dispersed phase), distributed throughout a continuous phase (dispersion medium). They are classified according to the particle diameter of the dispersed material. Molecular dispersions (less than 1 nm) Particles invisible in electron microscope Pass through semipermeable membranes and filter paper Particles do not settle down on standing Undergo rapid diffusion Eg . ordinary ions, glucose Dispersed Systems Classification of Dispersed Systems: 6 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

7. Colloidal dispersions (1 nm - o.5 um) – Particles not resolved by ordinary microscope, can be detected by electron microscope. Pass through filter paper but not pass through semipermeable membrane. Particles made to settle by centrifugation Diffuse very slowly E.g. colloidal silver solutions, natural and synthetic polymers. Classification of Dispersed Systems: 7 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

8. Coarse dispersions (> 0.5 um) Particles are visible under ordinary microscope Do not pass through filter paper or semipermeable membrane. Particles settle down under gravity - Do not diffuse E.g. emulsions, suspensions, red blood cells. 8 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

9. 1. Particle size: This influence colour of dispersion. Wavelength of light absorbed α 1/ Radius (small wave length) V I B G Y O R (large wavelength). Characteristics of dispersed phase 9 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

10. 2. Particle shape: Depends on the preparation method and affinity of dispersion medium This influence colour of dispersion. Shapes- spherical, rods, flakes, threads, ellipsoidal. Gold particles- spherical (red), disc (blue). 10 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

11. 3. Surface area: Particle size small- large surface area Effective catalyst, enhance solubility. 11 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

12. 4.Surface charge: Positive (+)= gelatin, aluminum. Negative (-) = acacia, tragacanth . Particle interior neutral, surface charged. Surface charge leads to stability of colloids because of repulsions. 12 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

13. Based of physical state of dispersed phase an dispersion medium. Based of nature of interaction between dispersed phase and dispersion medium. Based on molecular size in the dispersed phase. Based on appearance of colloids. Based on electric charge on dispersion phase. CLASSIFICATION OF COLLOIDS 13 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

14. Based on physical state of dispersed phase and dispersion medium 14 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

15. 1. LYOPHILIC COLLLOIDS 2. LYOPHOBIC COLLOIDS 3. ASSOCIATION COLLOIDS BASED ON NATURE OF INTERACTION BETWEEN DISPERSED PHASE AND DISPERSION MEDIUM 15 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

16. Colloidal solution in which the dispersed phase has a great affinity for the dispersion medium. They are also termed as intrinsic colloids. Such substances have tendency to pass into colloidal solution when brought in contact with dispersion medium. If the dispersion medium is water, they are called hydrophilic or emulsoids . The lyophilic colloids are generally self- stabilized. Reversible in nature and are heavily hydrated. Examples are starch, gelatin, rubber, protein etc. LYOPHILIC COLLOIDS 16 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

17. Colloidal solutions in which the dispersed phase has no affinity to the dispersion medium. These are also referred as extrinsic colloids. Such substances have no tendency to pass into colloidal solution when brought in contact with dispersion medium. The lyophobic colloids are relatively unstable. due to they are irreversible by nature and are stabilized by adding small amount of electrolyte. They are poorly hydrated. If the dispersion medium is water, the lyophobic colloids are called hyrophobic or suspenoids . Examples: sols of metals like Au, Ag, sols of metal hyroxides and sols of metal sulphides LYOPHOBIC COLLOIDS 17 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

18. These colloids behave as normal electrolytes at low concentrations but behave as colloids at higher concentrations. These associated colloids are also referred to as micelles. Sodium stearate behave as electrolyte in dilute solution but colloid in higher concentrations. Examples: Soaps , higher alkyl sulphonates , polythene oxide. ASSOCIATED COLLOIDS 18 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

19. MULTI MOLECULAR COLLOIDS Individual particles of the dispersed phase consists of aggregates of atoms or small molecules having diameter less than 10-7cm . The particles are held by weak vander waal’s forces. Example ; gold sol, sulphur sol. MACRO MOLECULAR COLLOIDS The particles of dispersed phase are sufficiently large in size enough to be of colloidal solution. These are called Natural Polymers. Examples are starch, cellulose and proteins. Based on molecular size in the dispersed phase. 19 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

20. SOLS When a colloidal solution appears as fluid. The sols are generally named as dispersion medium. When the dispersion medium is water, the sol is known as hydrosol or aquosol . When the dispersion medium is alcohol or benzene it is called alcosol and benzosol respectively. GELS When a colloidal solution appear as solid. The rigidity of gel varies from substance to substance. Examples : jelly, butter, cheese, curd. Based on appearance of colloids 20 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

21. POSITIVE COLLOIDS When dispersed phase in a colloidal solution carries a positive charge. Examples : Metal hyroxides like Fe(OH)3 , Al(OH)2 , methylene blue sol etc . NEGATIVE COLLOIDS When dispersed phase in a colloidal solution carries a negative charge. Examples : Ag sol, Cu sol BASED ON ELECTRICAL CHARGE ON DISPERSION PHASE 21 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

22. PHYSICAL Properties OPTICAL Properties KINETIC Properties ELECTRICAL Properties PROPERTIES OF COLLOIDS 22 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

23. Heterogeneity : Colloidal solutions consist of two phases-dispersed phase and dispersion medium. Visibility of dispersed particles: The dispersed particles present in them are not visible to the naked eye and they appear homogenous. Filterability: The colloidal particles pass through an ordinary filter paper. However, they can be retained by animal membranes, cellophane membrane and ultra filters. Stability: Lyophilic sols in general and lyophobic sols in the absence of substantial concentrations of electrolytes are quite stable. Colour : The colour of a colloidal solution depends upon the size of colloidal particles present in it. PHYSICAL PROPERTIES OF COLLOIDS 23 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

24. TYNDALL EFFECT When an intense converging beam of light is passed through a colloidal solution kept in dark, the path of the beam gets illuminated with a bluish light. The Tyndall effect is due to the scattering of light by colloidal particles. Tyndall effect is not exhibited by true solutions. This is because the particles present in a true solution are too small to scatter light. OPTICAL PROPERTIES OFCOLLOIDS 24 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

25. Used to observe tyndall effect, Dispersed particles appear as bright spots in dark back ground this capable of yielding pictures of actual particles size, shape and structure of colloidal particles. Used to determine zeta potential. ULTRA MICROSCOPE (Dark-field microscope) 25 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

26. depend on tyndall effect. used to give information about particle size and shape and for determination of molecular weight 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 LIGHT SCATTERING METHOD 26 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12.

27. The continuous zigzag movement of the colloidal particles in the dispersion medium in a colloidal solution is called Brownian movement. Brownian movement is due to the unequal bombardments of the moving molecules of dispersion medium on colloidal particles. The Brownian movement decreases with an increase in the size of colloidal particle. This is why suspensions do not exhibit this type of movement. KINETIC PROPERTIES OF COLLOIDS Used to detect stability of system, molecular weight of particles, transport kinetics. 27 R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. BROWNIAN MOVEMENT

28. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 28 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.

29. Particles diffuse spontaneously from a region of higher concentration to one of lower concentration until the concentration of the system is equilibrium. Diffusion is a direct result of Brownian movement. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 29 DIFFUSION

30. Ficks Ist law: states that particles diffuse spontaneously from a region of high concentration to region of low concentration until diffusion equilibrium is attained. dq = -Ds (dc/ dx ) dt Dq = quantity of drug diffused D = diffusion coefficient S = plane area dC = concentration change dx = distance travelled Dt = time taken for diffusion Application: molecular weight determination. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 30

31. The velocity v of sedimentation of spherical particles having a density ρ in a medium of density ρ o and a viscosity is given by stokes‘s Law v = d 2 ( ρi-ρe )g/18η V = rate of sedimentation D = diameter of particles ρ = density of internal phase and external phase g = gravitational constant η = viscosity of medium This law obeys only if the particles should be spherical Stokes equation about only 5μm. Brownian movement becomes active sedimentation will becomes slow due to gravity, promotes mixing. A strong force must be applied to bring sedimentation Ultracentruge is used for the complete sedimentation Ultracentrifuge can produce a force one million times that of gravity R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 31 SEDIMENTATION

32. Applications: 1. Molecular weight estimation 2. Study micellar properties of drug. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 32

33. van 't hoff equation: π = cRT Can be used to determine the molecular weight of colloid in dilute solution. ( where C = the grams of solute / liter of solution, M = molecular weight) π/C = RT/M Kinetic Properties of Colloids π = osmotic pressure R= molar gas constant R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 33 Osmotic pressure

34. 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 Spherocolloids dispersions of low viscosity Linear particles more viscous dispersions R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 34 viscosity

35. Surface charge Electrical double layer Zeta potential ELECTROPHORESIS Electro-osmosis Sedimentation Potential ( donnan effect) Steaming Potential R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 35 Electric properties

36. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 36 Electrical double layer

37. Surface charge: 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. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 37

38. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 38 Zeta potential Zeta Potential is the electric potential at the shear plane of a particle.

39. Particles within a colloidal dispersion carry charges that contribute to the net charge of a particle. Used in predicting stability of colloidal dispersion. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 39

40. The movement of colloidal particles towards a particular electrode under the influence of an electric field. If the colloidal particles carry positive charge, they move towards cathode when subjected to an electric field and vice versa. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 40 ELECTROPHORESIS

41. 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. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 41 Electro-osmosis

42. The movement of dispersion medium under the influence of an electric field in the situation when the movement of colloidal particles is prevented with the help of a suitable membrane. During electrosmosis , colloidal particles are checked and it is the dispersion medium that moves towards the oppositely charged electrode. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 42

43. The sedimentation potential also called the ( Donnan membrane 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. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 43 Sedimentation Potential ( Donnan effect)

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45. Differs from electro-osmosis in that the potential is created by forcing a liquid to flow through a bed or plug of particles. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 45 Streaming Potential

46. Breakage of potential energy barrier leads to precipitation/ agglomeration. Instability Methods: 1. Reducing height of potential barrier. 2. Increasing the kinetic energy, reduces potential energy. Instability reasons: 1. Removal of electrolyte ( 1% minimum) 2. Addition of electrolyte ( 2%minimum ) 3. Addition of electrolytes of opposite charge ( 2% minimum) 4. Addition of oppositely charged colloid ( 2% minimum). R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 46 Effect of electrolytes in colloids

47. 1.Removal of electrolyte (1% minimum) Colloids + electrolytes ^ stable colloidal dispersion Dialysis = remove Electrolytes --- Particles coagulate ^Settle to bottom. 2.Addition of electrolyte (2% minimum) Stable colloidal dispersion + excess electrolyte electrolyte --- Accumulate ^instability. 3. Addition of electrolytes of opposite charge (2% minimum) Stable colloidal dispersion + electrolyte opposite charge -- attractions between particles ^ Flocculation of particles. Schulze-Hardy Rule: Precipitating power α ionic charge Al+3>Ba+2>Na+ So4 -2> Cl 4. Addition of oppositely charged colloid (2% minimum) Bismuth colloids (+) + Tragacanth colloids (-) ^Coagulation. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 47

48. 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 The addition of less polar solvent renders the solvent mixture unfavourable for the colloids solubility. R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 48 Stability of colloids

49. Coacervation is 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 ). R VIJAYAKUMAR., M Pharm.Asst Professor, VCP.,Erode-12. 49 Coacervation

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