Emulsions and Creams Notes

Learning Outcomes

• Describe different types of emulsions
• Uses of emulsions and advantages/disadvantages
• Describe tests to determine type of emulsion formed
• Describe different types of film formation
• Describe different types of emulsifiers and give examples

Types of Emulsions

• Single emulsion
  • o/w (oil in water)
  • w/o (water in oil)
• Double emulsion
  • o/w/o
  • w/o/w

Emulsions - Oral

• Liquid paraffin emulsion
  • Used as laxative
  • o/w
  • Flavor in aqueous phase

Emulsions - Parenteral

• Total Parenteral Nutrition
  • Amino acids, carbohydrates, lipids
  • Intralipid® is IV fat/lipid emulsion
  • Need to be careful of droplet size!!!

Emulsion and cream - External application

• Sunscreens
• Moisturizers
• Drug delivery
• Emulsions and Creams (thicker emulsions)
  • Emulsions and creams fundamentally unstable
  • Absence of emulsifying agent, will separate
  • Oil and water shaken together…

Microemulsions

• Microemulsions are another type of emulsion
  • Homogeneous, transparent systems that are thermodynamically stable
  • Form spontaneously when components mixed in appropriate ratios
  • Dispersions of oil in water but droplet size is much smaller than coarse emulsions
    • 5-140nm
    • Essentially swollen micellar systems
• Need very low interfacial tension
  • Requires use of two surfactants
    • Surfactant and co-surfactant
  • Require larger amounts of surfactant in formulation
  • Advantages over traditional emulsions: transparency and stability

Advantages of Emulsions

• Administer drug to patients with swallowing difficulties (liquid)
• Disguise taste or smell of oils or oil-soluble drugs
• Improve absorption of poorly soluble drugs
• Controlled release of drug from parenteral formulation
• Protect drug from oxidation or hydrolysis
• Deliver nutrients and vitamins by IV injection
• Serve as a vehicle for topical administration of drugs

Disadvantages of Emulsions

• Thermodynamically unstable
• Difficult to formulate
• Difficult to manufacture

What Makes a Good Emulsion?

• Physical stability (no phase separation)
• Appropriate flow properties
• Aesthetically and texturally pleasing
• If for oral use, acceptable taste
  • Use o/w emulsion for oral emulsions
  • Flavors and sweeteners in external phase
  • o/w emulsion will rinse/wash readily from mouth

External Use

• Can use o/w or w/o emulsions
  • w/o emulsions not water washable and can feel greasy, occlusive
  • o/w emulsions are water washable, non-occlusive, non-greasy
• Creams are semi-solid emulsions
  • Creams often used with weeping lesions as miscible with secretions and have drying effect
• Lotions are more liquid emulsions (although some lotions are also suspensions)

Determine Emulsion Type

• Dilution test
  • Emulsion that is o/w can be diluted, will wash off fingers easily
• Conductivity test
  • If water is continuous phase, have higher electrical conductivity
• Dye solubility test
  • Water-soluble dye added to emulsion, look at appearance

Thermodynamics of Emulsions

• Emulsions do NOT form spontaneously
  • Require energy input (mechanical agitation, vibration, heat)
  • Unstable systems as increased surface area of water or oil droplets
    • Increased free energy
    • Tend to reduce energy by coalescing to go back to 2 phases
  • Need to add third agent = emulsifying agent

Emulsifying Agents

• Aid in forming emulsions through three effects:
  • Reducing interfacial tension
  • Forming rigid interfacial film
  • Formation of an electrical double layer
    • Electrical double layer due to adsorption at interface with their charged or polar groups sticking out into aqueous phase

Mix of Emulsifiers

• Presence of more than one surfactant can help create a more complete film at interface
  • Contributes positively to stability (better emulsion)
  • Synergistic effect
    • Sodium cetyl sulphate (hydrophilic surfactant) used in combination with cholesterol (lipophilic surfactant) forms stable film due to their interaction on surface
    • Close packing of the two surfactants reduces interfacial tension > than either alone

Film Formation

• Emulsifying agents should readily form film around droplets
  • Barrier to coalescence
  • Adsorption at interface lowers interfacial tensions
  • Film must also have some degree of surface elasticity and should not thin or rupture when sandwiched between 2 droplets
  • If film is broken, should reform rapidly

Film Types

• Monomolecular film
  • synthetic and organic compounds (sodium lauryl sulfate) which lower interfacial tension and surface free energy
• Multimolecular film
  • Hydrophilic colloids
    • do not cause appreciable lowering of interfacial tension, efficiency lies in forming coherent film
    • Any hydrocolloid not adsorbed also thickens external phase (beneficial)
    • If hydrophilic polymer is ionic (gelatin, sodium alginate, sodium carboxymethylcellulose) film will be charged and exhibit zeta potential
    • May add further protection through electrical repulsion
• Solid particle films
  • If particles sufficiently wetted by both oil and water phases (but preferentially wetted by one phase), will accumulate at interface
  • If show high inter-particulate adhesion gives mechanically robust layer which enhances stability
  • Type of emulsion depends on preference of particles
    • If preferentially wet by aqueous phase (contact angle <90) forms o/w emulsion
    • If prefers oil, forms w/o emulsion

Solid Particle Films Examples

• o/w
  • Aluminum hydroxide
  • Magnesium hydroxide
  • Bentonite
• w/o
  • Talc
  • Carbon
  • Kaolin

Types of Emulsifiers

• Natural products
• Surface active agents (surfactants)
• Finely divided solids

Natural Products

• Polysaccharides
  • e.g. Acacia, tragacanth, sodium alginate, pectin, and agar
  • Biocompatible and can use for oral
  • Acacia produces stable and elegant emulsions
  • Acacia forms multimolecular film
  • Classed as primary emulsifying agent
  • Has low viscosity so creaming of emulsion can occur
  • Other polysaccharides tend to be secondary (auxiliary) emulsifying agents
• Sterols
  • Beeswax- used as stabilizer for w/o creams
  • Cholesterol and various fatty acid esters of cholesterol
  • Cholesterol is constituent of wool alcohols, obtained by fractionation
  • Very efficient emulsifier producing w/o emulsions
  • Mainly used in external applications
• Wool fat
  • Wool fat or lanolin contains a considerable amount of cholesterol esters
  • Absorb up to 50% of own weight in water
  • Forms w/o emulsion
  • Often used for emollient properties
  • Also used as emulsion stabilizer (auxiliary emulsifier)
  • Some patients exhibit sensitization to this material
  • Degree of odor
• Phospholipids:
  • Lecithin obtained from plants and animal sources
  • Produces o/w emulsions
  • Prone to microbial attack
  • Also oxidizes and darkens readily
  • Purified lecithins are principal emulsifiers in IV fat emulsions
  • Can provide stable fat emulsion with <1um diameter droplets
• Proteins:
  • Gelatin= natural emulsifying agent
  • Gelatin A has isoelectric point between 7 and 9
  • Gelatin B isoelectric point at pH5
  • Type A best used when it has a positive charge around pH3
  • Type B best used when has a negative charge (pH8)
  • Sign of charge needs to be considered when adding other agents to emulsion
  • All emulsifying agents should carry the same charge
  • E.g., if acacia being used (-ve) should use gelatin B under alkaline conditions

Surfactants: Anionic

• Alkali metals and ammonia soaps
  • Sodium, potassium, or ammonium salts of long-chain fatty acids such as oleic acid, stearic acid
  • May be made in situ
    • Oleic acid + ammonia= ammonium oleate
  • Example: Benzyl benzoate lotion
    • Benzyl benzoate (active ingredient)
    • Triethanolamine 0.5g
    • Oleic acid 2g
    • Water to 10mL
• Oleic acid + triethanolamine react to form surfactant in situ

Anionic Surfactants

• Soaps
  • Alkali Soaps (sodium palmitate) CH3(CH2)_{14}COO^-Na^+
  • Amine Soaps (triethanoleamine oleate) CH3(CH2)CH=CH(CH2)7COO^-NH^+(CH2CH2OH)_3
• Alkylsulfates (sodium laurylsulfate) CH3(CH2){11}OSO3^-Na^+
• Bile Salts (sodium cholate)

Anionic Surfactants Continued

• Soaps of divalent ions such as Ca^{2+} and Mg^{2+} are w/o type emulsifiers
  • Lime water (calcium hydroxide solution) + fatty acid (e.g., oleic acid) used in some preparations
    • Calcium oleate
  • Divalent ion = w/o emulsion
• Sulphates and sulphonated compounds produce o/w emulsion
  • Sodium lauryl sulphate (o/w emulsion)
  • Because of high water solubility, unable to form condensed film at o/w interface
  • Always used in conjunction with nonionic surfactant which produces complex condensed film at the interface; usually use cetostearyl alcohol

Cationic Surfactants

• Positively charged head group - quaternary ammonium salts, e.g. Cetrimide
• Produce o/w emulsions
• Poor emulsifiers by themselves (add auxiliary agent)
• Often used as antibacterials
• Example: Cetrimide cream
  • Cetrimide 5g
  • Cetostearyl alcohol 50g
  • Liquid Paraffin 500g
  • Water to 1000mL

Nonionic Surfactants

• Hundreds of these
• Compatible with ionic compounds
• Less susceptible to pH
• Examples:
  • Fatty Alcohols CH3(CH2)xCH2OH (x=11,13,15, cetyl, 17, tearyl alcohol)
  • Polysorbates, Tweens: PEG-Sorbitan Fatty Acids Esters
  • Spans: Sorbitan Esters of Fatty Acids
  • Partial Fatty Acid Esters of
  • Brij Polyethyleneglycol (PEG) Ether (PEG-200 ether, Bj30)
  • Cremopher: Polyethyleneglycall (IG) Fatty Acid Ester (PEG-400

Finely Divided Solids

• Adsorb at the oil-water interface to physically prevent coalescence
• If particles preferentially wetted by aqueous phase - usually have o/w emulsion or if preferentially wet by oil - w/o emulsion
• Common examples: Bentonite, Veegum, Magnesium hydroxide, Colloidal silicon dioxide, Aluminum hydroxide
• Example: Liquid Paraffin Emulsion
  • Liquid Paraffin
  • Magnesium Hydroxide
  • Water