Coarse Dispersion

1. Coarse Dispersion Emulsion

2. Emulsions are Mixtures of oily substances & aqueous substances, stabilized by an emulsifier. • The suspended droplets are called the dispersed phase or inner phase (diameter 0.1-100 µm). • The surrounding fluid is called the outer phase. • Emulsions are very favorable in cosmetics industry. • This is because they can incorporate both hydrophilic & lipophilic substances. • The hydrophilic phase gives a Humectant action while the Emollient action is produced by the lipophilic phase. • Another advantage is their suitable η, which improves application.

3. Advantages of emulsion in pharmacy & medicine: • ………………………………….. • …………………………………..; • …………………………………..; • …………………………………..; • …………………………………...

4. Emulsion type & Means of detiction: 1. Conductivity test; 2. Dilution test. 3. Dye-solubility test.

5. Formation & Breakdown of Dispersed Liquid Droplets. Two (2) competing processes give emulsion: • Non spontaneous: • Spontaneous:

6. Dispersion Process to Form Droplets Figure 22.5 Important: • Time of Agitation (1 – 5 min), after that the N of coalescence droplets = N of formed droplets. • Intermittent shaking ( gives more droplets) • Rapid & continuous shaking gives (hinder the breakdown of droplets) High speed Mixers, blinders & colloidal mills are recommended. Flocculation Coalescence Aggregation .

7. Emulsifying Agent Pharmacist must take in consideration the following factors: • …………………………………... • …………………………………..; • …………………………………...

8. Desirable Properties of a.e.: • Be surfaceactive & ↓γ below 10 dyne /cm. • Be adsorbed quickly around the dispersed drops as a condensednon-adherent film that will prevent coalescence. • …………………………………..; • …………………………………..; • …………………………………..

9. Interfacial Tension • Total surface area = N of particles . Surface area of each particle. • Film Formation Figure 22.6 To be efficient the film must: • …………………………………..; • …………………………………..; • …………………………………...

10. Electrical potential • ↑ viscosity Table 22-3 • [emulsifier] Example page 325

11. Classifications & Mechanisms of Action of Emulsifying Agents Table 22-4 • Classification in accordance with the Type of the film they form at the Interface between the two phases. II. In accordance to their chemical structure.

12. Classification according to the type of the formed film (figure 22-6): • MONOMOLECULAR FILMS Stabilize an emulsion by forming a monolayer of adsorbed molecules or ions at the O/W interface: • In accordance with Gibbs' law, the presence of an interfacial excess necessitates a ↓ in .

13. More significant is the fact that the droplets are surrounded now by a coherent monolayer that prevents coalescence between approaching droplets. • If the emulsifier is ionized, the presence of strongly charged & mutually repelling droplets ↑ the stability of the system. • With unionized, nonionic surface active agents, the particles may still carry a charge.

14. MULTIMOLECULAR FILMS Hydrated lyophilic colloids form multimolecular films around droplets of dispersed oil. These hydrophilic colloids are adsorbed at the interface. They do not cause an appreciable ↓ in . Their efficiency depends on their ability to form strongcoherentmultimolecular films. These act as a coating around the droplets & render them highlyresistant to coalescence. Any hydrocolloid not adsorbed at the interface ↑the η of the continuous aqueous phase.

15. Solid ParticleFilms 1st requirement: Small solid particlesthat are wetted to some degree by both aqueous & oily liquid phases act as e.a. 2nd requirement: Is that the particles are small in relation to the droplets of the dispersed phase.

16. Classification According to the Chemical Structure There is some correlation between this classification & that based on the mechanism of action. • For example: The majority of emulsifiers forming monomolecular films are synthetic, organic materials. Most of the emulsifiers that form multimolecular films are obtained from natural sources & are organic. A 3rd group (solid particles), invariably inorganic, that form films composed of finely divided solid particles. • Accordingly, the classification, adopted divides e.a into synthetic, natural, & finelydispersed solids. • A 4th group, the auxiliary materials are weak emulsifiers.

17. Synthetic Emulsifying Agents • These e.a. may be subdivided into: Anionic; Cationic &; Non-ionic. • Anionics: • The K, Na, & NH4 salts of lauric & oleic acids are soluble in water & are good O/W e.a.: • They have a disagreeable taste & are irritating to the GI tract.

18. Solutions of alkali soaps, have a ↑ pH. 1. …………………………………... The free fatty acid is ineffective as an emulsifier. • …………………………………... • Salts formed from a fattyacid & an organic amine (T.E.A): • These are limited to external preparations.

19. Their alkalinity is considerably < than that of the alkali soaps &; • They are active as emulsifiers down to around pH 8. • Are < irritating than the alkali soaps. • Sulfated alcohols (neutralized sulfuric acid esters of such fatty alcohols) as lauryl & cetyl alcohol: • ………………………………….., • ………………………………….., • …………………………………...

20. Cationics e.g. is Cetyltrimethyl-ammonium bromide CH3(CH2)14(CH2)N+(CH2)3Br - …………………………………... This makes them desirable in emulsified anti-infective products such as skin lotions & creams. ………………………………….. (normal pH of the skin). …………………………………..(stabilizing or auxiliary e.a. such as cetostearyl alcohol is used).

21. They should not be used in the same formulation with anionic emulsifiers: The incompatibility may not be immediatelyapparent as a ppt, but virtually all of the desired antibacterial activity will generally have been lost.

22. Non-ionics They are not susceptible to pH changes & the presence of electrolytes. The most frequently used are the: • glyceryl esters, • polyoxyethylene glycol esters & ethers, • sorbitan fatty acid esters & their polyoxyethylene derivatives, • polyoxy ethylen / polyoxypropylene block copolymers.

23. Polyoxyethylene stearate Glyceryl mono stearate Span 80 [sorbitanoleate] Tween 80

24. Glyceryl monostearate is used widely as an auxiliary agent. Sorbitan fatty acid eaters, (SPANs) are nonionic oil soluble emulsifiers that promote W/O emulsions. The polyoxyethylene sorbitan fatty acid esters, (TWEENs) are water-soluble derivatives that favor O/W emulsions. Polyoxyethylene glycol esters (PEGs esters), [i.e. monostearate. Polyoxyethylene/poly oxypropylene block copolymers (poloxamers) = Oxyethylene + Oxypropylene.

25. Poloxamers have been used in: The formulation of I.V. injection; It can impart: • ………………………………….. & • ………………………………….. : Via steric stabilization. When blended properly, the nonionics produce fine-textured stable emulsions.

26. Natural Emulsifying Agents: • Acacia is a carbohydrate gum that is soluble in water & forms O/W emulsions. • Emulsions prepared with acacia are stable over a widepH range. • It is necessary to preserve acacia emulsions against microbial attack. • Gelatin, a protein, has been used for many years as an emulsifying agent. • It can have 2 iso-electric points, depending on the method of preparation.

27. Type A gelatin, (acid treated precursor), [iso-electric point ≈ pH 7 & 9]. Type A acts around pH 3, where it is +ly charged. Type B gelatin, (alkali treated precursor), [isoelectric point ≈ pH 5]. Type B gelatin is best used around pH 8, where it is -ly charged. To avoid an incompatibility, all e.a. should carry the same sign. Gums such as tragacanth, acacia, or agar that are -ly charged are to be used with gelatin, then Type B material should be used at an alkaline pH.

28. Lecithin obtained from both plant (eg, soybean) & animal (eg, egg yolk) sources. The primary component of most lecithins is phosphatidylcholine. Frequently, lecithins that are used as emulsifiers also contain mixtures of phosphatides, including: • phosphatidylserine, • phosphatidylinositol, • phosphatidylethanolamine, & • phosphatidic acid. Although phosphatidyicholine is a zwitterionic compound, The presence of other phosphatides imparts a net (-) charge to dispersed particles.

29. It is an excellent emulsifier for naturally occurring oils [i.e. soy, corn, or safflower], Highly stable O/W emulsions can be formed with these oils. Purified lecithins from soy or egg yolk are the principal emulsifiers for I.V. fat emulsions. Lecithin stable emulsions with droplet Ø < 1µm.

30. The excellent stability observed with these emulsions may a result of: • …………………………………..; • …………………………………... As an emulsifier, lecithin  the best results at a pH ≈ 8,

31. The source of lecithin can influence Its : • …………………………………..; • …………………………………..; • …………………………………... Cholesterol It is a major constituent of wool alcohols, It is obtained by the saponification & fractionation of wool fat. It gives wool fat its capacity to absorb water & form W/O emulsion.

32. FINELY DISPERSED SOLIDS They form particulate films around the dispersed droplets, producing emulsions that are coarse grained & have considerable physical stability. It appears possible that any solid can act as an emulsifying agent of this type, provided it is reduced to a sufficiently fine powder. In practice, the group of compounds used most frequently are the colloidal Bys. Bentonite is a white to gray, odorless & tasteless powder that swells in the presence of water to form a translucent suspension with a pH ≈ 9. Depending on the sequence of mixing it is possible to prepare both O/W & W/O emulsions.

33. When an O/W emulsion is desired, the bentonite is first disused in water & allowed to hydrate so as to form a magma. The oil phase is then added gradually with constant titration. Because the aqueous phase is always in excess, the O/W emulsion type is favored. To prepare a W/0 emulsion, the bentonite first dispersed in oil, the water is then added gradually, Although Veegum is used as a solid particle emulsifying agent it is employed most extensively as a stabilizer in cosmetic lotions & creams. Concentrations of less than 1% Veegum will stabilize an emulsion containing anionic or nonionic emulsifying agents.

34. AUXILIARY EMULSIFYING AGENTS (table 22-5) They include those compounds that are normally unable themselvesof forming stable emulsions. Their main use lies in their ability to function as thickening agents and thereby help stabilize the emulsion.

35. Emulsifying Agents & Emulsion Type: The HLB number is an index describing the hydrophiliclipophilic balance. A hydrophilic emulsifier possess a ↑HLB number, These are O/W emulsifiers. A lipophilic emulsifier has a ↓ HLB number & belongs to the W/O emulsifier group. Table 22-6

36. Griffin Scale: • 10 50 Lipophilic Hydrophilic Table 22-7

37. Rate of Coalescence & Emulsion Type Davies indicates that type of emulsion is controlled by the relative coalescence rates of oil droplets dispersed in the oil. Rate of Coalescence: Rate 1 = C1e-w1/RT C1 = Collision factor of phase 1 Rate 2 = C2e-w2/RT C2 = Collision factor of phase 2 C1 1/η C1 volume of phase W = the required work that must be crossed in order to give coalescence W depends on ζ potential. Rule of Davies: HLB < 7 → W/O HLB > 7 → O/W

38. Preparation of Emulsions: • Selection of e.a. Pharmacist must ensure the following properties of e.a.: • …………………………………..; • …………………………………..; • …………………………………..; • …………………………………... Therefore, e.a. suitable for skin cream may be unsuitable for oral emulsion.

39. Griffin method Known as HLB system: Required HLB value is the HLB valuerequired by a particular material to be emulsified effectively. The HLB value is an algebraically additive. This means that: One with HLB > the required + One with HLB < the required The required HLB value. Tables 22-6, 22-7, 22-8.

40. The most important parameters to achieve a stable emulsion are: • Using e.a. with the required HLB number; • Using the required quantities of the surfactant. Example page 329. • Ternary diagram to have an idea about the [e.a.]

41. Methods of calculation of HLB numbers: • Unknown Chemical Structure: …………………………………... • Known chemical structure: …………………………………..

42. Utility of the HLB approach is to: • Provide the formulator with an idea about hydrophilicity & lipophilicity in a particular surfactant. • Relate the emulsifying & solubilizing properties of the surfactant to the others surfactants. The formulator still needs to confirm experimentally that a particular formulation will  a stable emulsion. Table 22-9, 22-10

43. Mixed Emulsifying Agents The use of a blend of e.a. may: • …………………………………..; • …………………………………..; • …………………………………... Regarding the 2nd point: Schulman & Cockbain showed that: • The complex (Na Cetyl sulfate – Elaidyl alcohol) ↑ the stability of O/W emulsion. • There is nocomplex formation if Olyl alcohol is used in stead of its isomer Elaidyl. • The mixture (Na Cetyl sulfate + Olyl alcohol) doesn’t O/W emulsion.

44. Steric Stabilization ( Non-ionic e.a. or protective polymers). Method of preparation of emulsion: • In pharmacy [mortar & pestle]: For oral use (O/W emulsion) using gums such as arabic or tragaganth • Industrial preparation Homogenizer, colloidal mill, …etc.

45. Stability of Emulsions: • ………….. stability (the most important); • ………….. stability; • ………….. stability (preservatives must have affinity for both water & oil phases). The 3 major phenomena associated with physical stability are: • …………………………………..; • …………………………………..; • …………………………………...

46. The upward or downward movement of dispersed droplets relative to the continuous phase, (creaming & sedimentation); • The aggregation & possible coalescence of the dispersed droplets to the separate phase; • Inversion, in which an O/W emulsion inverts to become a W/O emulsion & vice versa.

47. Parameters that influence emulsion stability: • …………………………………..; • …………………………………..; • …………………………………... Compact films are obtained from mixtures of e.a. The ↑elasticity of the film, resistance to coalescence.

48. 4. ξ-Potential In O/W emulsion, we will have a ξ potential, while in W/O emulsion, the surfactant can’t  ξ, Why? Because the lipophilic chains can’t attract water ions.

49. 5. The Emulsifying agent 6. The viscosity of the external phase This will ↓ the motility of the internal phase droplets making it more difficult for them to collide with each other. This can be achieved by the addition of suitable thickening agents.

50. Assessment of emulsion stability: Factors which may ↓ the stability of emulsions: • ………………………………….., • ………………………………….., • ………………………………….., • ………………………………….., & • …………………………………... .