Understanding Emulsions: Types and Properties

• Emulsions are thermodynamically unstable systems where one immiscible liquid is dispersed as droplets within another liquid.
• The dispersed liquid is the internal phase, while the liquid it is dispersed in is the external (or continuous) phase.
• A third substance, an emulsifying agent, is required to create a stable emulsion.

Emulsion Types

• Oil-in-Water (o/w) emulsions have an oily internal phase and an aqueous external phase.
• Water-in-Oil (w/o) emulsions have an aqueous internal phase and an oily external phase.
• o/w emulsions can be diluted with water; w/o emulsions can be diluted with oil.
• Multiple emulsions have multiple layers of dispersed phases like oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w).

Macroemulsions vs. Microemulsions

• Microemulsions form spontaneously when oil and water phases are mixed with specific surfactants.
• The type of microemulsion depends on the oi and surfactants used.
• Microemulsions have droplets sized between 100 and 1,000 Å.
• Macroemulsions have larger droplets around 5,000 Å
• Microemulsions can improve oral drug absorption.
• Microemulsions can enhance transdermal drug delivery due to their small droplet size.
• Macroemulsions appear white and opaque and are thermodynamically unstable.
• Microemulsions can be cloudy, translucent or transparent and are thermodynamically stable.
• Macroemulsions require substantial energy for production, while microemulsions form spontaneously.

Determination Tests for Emulsion Type

• Miscibility Test: o/w emulsions remain stable upon dilution with water, w/o emulsions remain stable upon dilution with oil.
• Staining Test: Oil-soluble stain added to the emulsion on a slide viewed under microscope. Staining globules indicate o/w, staining background indicates w/o.
• Conductivity Test: o/w emulsions conduct electricity because water is the continuous phase.

Emulsions by Physical State and Administration Route

• Emulsions can be liquid or semisolid.
• Liquid emulsions are administered orally (o/w), topically or parenterally (I.V. o/w, I.M. and S.C. w/o).
• Semisolid emulsions are used topically as lotions, creams, and liniments.
• The choice between o/w and w/o depends on the therapeutic agent, desired effect, and administration route.

Purpose and Benefits of Emulsions

• Enables stable mixtures of immiscible liquids, useful for liquid drug dosage forms.
• Oral o/w emulsions can improve taste-masking.
• o/w emulsions act as carriers for lipophilic drugs, improving oral bioavailability.
• I.V. o/w emulsions administer nutritive oils/vitamins to patients unable to ingest food.
• I.M. and S.C w/o emulsions prolong drug effects by controlling diffusion rates.
• Topical o/w emulsions are easily removed with water and can reduce skin irritation.
• Topical w/o emulsions soften skin and resist water removal.
• Reduced particle size in emulsions can enhance percutaneous absorption.

Acceptable Emulsion Characteristics

• Uniform distribution of dispersed phase globules
• Pleasing appearance and texture
• Appropriate flavor for oral use
• Easy spreadability for external use
• Physical stability (no flocculation, creaming, sedimentation, or coalescence)
• Absence of microbial deterioration

Disadvantages of Emulsions

• Thermodynamically unstable, require careful formulation.
• Require shaking before dose measurement, but dose accuracy is still lower than solutions.
• Storage conditions can cause creaming or cracking.
• Prone to microbial contamination, leading to cracking.
• More bulky than solid dosage forms.

Gibbs Free Energy in an Emulsion

• Equation: ΔG = ΔA γ, where A is total surface area, γ is interfacial tension.
• Stable emulsions require large A and small G, achieved by decreasing γ, which will decrease self-attraction of dispersed phase particles.

Theories of Emulsification

• Surface Tension Theory: Emulsifying agents reduce interfacial tension between liquids. They facilitate the breakup of large globules into smaller ones.
• Oriented-Wedge Theory: Emulsifying agents form monomolecular layers around droplets. Agents with greater hydrophilic character promote o/w emulsions, hydrophobic favor w/o.
• Plastic or Interfacial Film Theory: Emulsifying agents create a film between liquids. The film prevents dispersed phase contact and coalescence. The stability depends on film toughness/flexibility.

Factors Affecting Emulsion Formation

• Emulsifying agents
• pH
• Ratio of internal to external phases

Criteria for Selecting Emulsifying Agents

• Compatibility with other ingredients
• Stability during preparation/storage
• Nontoxic and safe for consumption
• Promotion of emulsification

Types of Emulsifying Agents

• Carbohydrate Materials: Acacia, tragacanth, agar. Typically form o/w emulsions.
• Protein Substances: Gelatin, egg white, casein which produce o/w emulsions.
• High Molecular Weight Alcohols: Stearyl alcohol, cetyl alcohol which are used as thickening agents and stabilizers for topical o/w emulsions. Cholesterol derivatives can promote w/o emulsions for external use.
• Surfactants: Amphiphilic molecules (hydrophilic heads/lipophilic tails). Can be anionic, cationic, or nonionic.
• Finely Divided Solids: Colloidal clays like bentonite which form o/w or w/o emulsions.

Mechanisms of Action of Emulsifying Agents

• Monomolecular: Lower interfacial tension with coherent flexible film (e.g., Potassium laurate, Tween).
• Multimolecular: Strong rigid film formed by hydrocolloids which produce O/W emulsion like Acacia and Gelatin.
• Solid Particles: Film formed by ionized solid particles (e.g., Bentonite)
• Auxiliary: Lipophilic (High Molecular Weight Alcohols) and Hydrophilic (Tragacanth and agar).

Hydrophilic-Lipophilic Balance (HLB) System

• Classifies emulsifying agents based on polarity (HLB value).
• Values range from 1 to 20 (sometimes up to 40)
• HLB values of 3-6 are lipophilic and favor w/o emulsions.
• HLB values of 8-18 favor o/w emulsions.
• Activity based on HLB: Antifoaming (1-3), w/o emulsifiers (3-6), wetting agents (7-9), o/w emulsifiers (8-18), solubilizers (15-20), detergents (13-16).
• The HLB system is used for calculating the relative quantities of SAA emulsifiers that are necessary for producing a physically stable emulsion.

Required HLB

• Emulsifying agents should have the same HLB value as the oleaginous phase.
• Each oil has a "Required HLB" value
• Mineral oil has an HLB of 4 for w/o and 10.5 for o/w emulsions.

Blending Emulsifying Agents

• HLB values are additive (Total HLB= fraction A + fraction B).
• Total HLB = HLBA (X) + HLBB (1-X)

Small-Scale Emulsion Preparation

• Equipment: Mortar and pestle, mechanical blenders, prescription bottles
• Techniques: Continental/dry gum method, English/wet gum method, bottle/Forbes bottle method.
• Continental/Dry Gum Method: 4 parts oil, 2 parts water, 1 part gum (4:2:1). Triturate gum with oil, add water all at once, then triturate continuously.
• English/Wet Gum Method: Create gum mucilage with water, slowly incorporate oil.
• Bottle/Forbes Bottle Method: For volatile oils, shake powdered acacia with oil, add water in portions, and shake after each addition.
• Forbes bottle method is not suited for viscous oils.

Emulsion Preparation Considerations

• Dissolve water-soluble ingredients in aqueous phase, oil-soluble in oil phase.
• Dissolve solids like preservatives and colorants in water before adding to the primary emulsion.
• Warm both phases if using fats/waxes/solid SAA emulsifiers
• Add substances that might interfere with emulsion stability at the end.
• Avoid adding alcohol directly to the primary emulsion.

Auxiliary Methods

• Homogenizers can improve emulsion quality by reducing globule size.

In Situ Soap Method (Nascent soap method)

• Creates calcium soaps (w/o emulsions) by mixing vegetable oils with limewater.

Large-Scale Preparation

• Mixing tanks with high-speed impellers, Colloid mills or large homogenizers are used.

Instability of Emulsions

• Flocculation
• Creaming or sedimentation
• Coalescence or aggregation
• Cracking or breaking
• Phase separation
• Flocculation: Droplets aggregate to form clumps (floccules) which rise or settle in the emulsion depending on their densities.
• Creaming: Globules rise to the top or fall to the bottom. According to Stokes' equation, larger particle size, greater density difference, and lower viscosity increase creaming.
• Coalescence: Droplets merge into larger droplets, leading to complete phase separation (breaking/cracking). This process is irreversible.

Phase Inversion

• Conversion between o/w and w/o emulsions which occurs when the dispersed phase exceed a theoretical maximum of 74% of the total volume.

Storage Considerations

• Protect against extremes of cold and heat.
• Protect against light, air, and contaminating microorganisms.
• Use light-resistant containers for light-sensitive emulsions.
• Include antioxidants and ensure tight closure for emulsions susceptible to oxidation.

Preservation of Emulsions

• Include fungistatic preservatives (e.g., methylparaben, propylparaben) in the aqueous phase.
• Add 12-15% alcohol to oral o/w emulsions for preservation.

Therapeutic Examples

• Oral Emulsions:
  • Mineral Oil Emulsion: o/w emulsion as a lubricating cathartic.
  • Castor Oil Emulsion: Laxative for constipation and colon preparation.
  • Simethicone Emulsion: Defoaming agent for gastrointestinal gas.
• Topical Emulsions:
  • Lotions: Many hand/body lotions are o/w emulsions.
  • Shampoos: Can be emulsion dosage forms for hair/scalp cleansing.
  • Liniments: Alcoholic/oleaginous solutions or emulsions intended for rubbing on the skin.