EMULSIONS

1. EMULSIONS • Heterogeneous systems consisting of at least one immiscible liquid phase intimately dispersed throughout a second phase in the form of droplets or globules

2. CHARACTERISTICS • Thermodynamically unstable mixtures • Dispersed particles range in diameter from 0.1 to 100 mm • Range from lotions with relatively low viscosity to semi-solid ointments and creams

3. PURPOSE • Oral • palatabilization of drug of objectionable taste • absorption of water-insoluble liquids • enhanced bioavailability of lipophilic drugs • Topical • oils used as emollients or protectants of skin, when emulsified they feel less greasy • enhanced transdermal absorption

4. oil water Final emulsion : o/w Final emulsion : w/o Emulsification Process • two competing mechanisms • the dispersion of one liquid throughout another as droplets (energy input, increase DG) • reduction in DG through coalescence of formed droplets

5. Emulsifying Agent • added to reduce the rate of coalescence • stabilizes emulsion • mechanisms • reduces the interfacial tension between 2 immiscible phases • forms an interfacial film around droplet • steric/electrostatic effects

6. Interfacial tension lowering • surfactants adsorb at interface g csolute

7. monomolecular film • surfactant forms a monolayer of adsorbed molecules at the interface • droplet phase cannot come into contact • possible electrostatic repulsion

8. multimolecular films • hydrated lyophilic colloids adsorbed onto surface (dispersed oil) • do not reduce interfacial tension but form strong coating

9. Solid Particle Films • small particles that are wetted to a degree by both aqueous and non-aqueous liquid phases • particles must be small compared to droplets

10. Emulsifying Agents • Desirable properties • surface active (reduce g to < 10 dynes/cm) • be adsorbed quickly around the droplets • impart an adequate electrical charge to droplet • increase the viscosity of the emulsion • be effective at low concentrations • be resistant to chemical degradation • be compatible with other components • nontoxic and nonirritating • odorless, colorless, tasteless

11. Chemical Types synthetic • divided into anionic, nonionic • anionic • soft soaps (ex. potassium laurate) • good O/W emulsifiers • stable only in alkaline pH • weak electrolytes which require charge to be effective  pH important • incompatible with multivalent cations • have a disagreeable taste and are irritating to GI • limited to external use • hard soaps (ex. Ca-oleate) • oil soluble, favor W/O emulsions • weak electrolytes, dependent on pH • limited to external use

12. nonionic • ex. sorbitan monooleate (Span 80), polysorbate 80 (Tween 80) • neutral and stable over wide pH range • insensitive to electrolyte conc’n • heat stable • may require additional viscosity enhancing agent • can form O/W or W/O

13. natural • acacia • forms O/W emulsions that are stable over a wide pH range • gelatin • type A : pI = 7-9, works best at pH 3 • type B : pI = 5, works best at pH 8 • both acacia and gelatin form multimolecular films

14. lecithin • phospholipid • very hydrophilic, produces O/W emulsions • liable to microbial attack and oxidation • forms a monomolecular film • cholesterol • nonionic, used to make W/O emulsions • forms a monomolecular film

15. Auxiliary Emulsifiers • compounds which are normally incapable of forming stable emulsions alone • mainly used as thickening agents • lipophilic, stabilizing O/W • cetyl alcohol, glyceryl monostearate, • hydrophilic, stabilizing O/W • methylcellulose, NaCMC

16. Choosing an Emulsifying Agent • HLB • HLB < 10 : lipophilic • HLB > 10 : hydrophilic • for O/W emulsions, want HLB of 8-18 • for W/O emulsions, want HLB of 3-6 • choose an emulsifying agent which has an HLB of the same value as the oil phase

17. HLB values

18. can combine emulsifying agents to obtain desired HLB • HLB values are additive • be aware of polarity of material being emulsified • required HLB • the HLB required of a material to be effectively emulsified

19. Required HLB

20. Example 5 g of emulsifying agent is called for in an oil in water emulsion of 50 g liquid petrolatum in water. The total mass of the emulsion is 100g. You decide to use sorbitan monooleate and polyoxyethylene 20 as the emulsifying agents. Determine the amount of required of each.

21. Example Determine the amounts of emulsifying agent to prepare the following oil-in-water emulsion : light mineral oil 31% beeswax 5 % cottonseed oil 2 % polyoxyethylene 20 sorbitan monolaurate sorbitan monostearate water 55% 7 %

22. Physical Stability prevention of coalescence/phase separation • creaming or sedimentation • upward or downward movement of dispersed droplets respectively • adversely affects dosage • easily reversible with mild agitation • affected by : • droplet size • reduce as much as possible (decr. free energy, decr. settling rate) - < 5 mm • viscosity of external phase • hydrocolloids for O/W • viscous oils, fatty alcohols, fatty acids for W/O

23. coalescence or breaking • formation of a separate layer • irreversible phase inversion • change from an O/W to a W/O, or vice versa • sometimes results from addition of an electrolyte • ex. sodium stearate plus calcium • results from cooling an emulsion • phase inversion temperature (PIT) • greater PIT, the greater the resistance to inversion • phase-volume ratio should be 50% (approximates close packing condition)

24. Preparation • oil phase and water phase components heated separately • pump one phase into other phase with agitation • mechanical stirrers • homogenizers • colloid mills • cool emulsion, then homogenize • package