Understanding Emulsions: Types and Properties

• Emulsions are thermodynamically unstable systems where one immiscible liquid is dispersed as droplets within another.
• The dispersed liquid is the internal phase, and the surrounding liquid is the external or continuous phase.
• Emulsifying agents are often needed to stabilize emulsions.

Emulsion Types

• Oil-in-water (o/w) emulsions have an oily internal phase dispersed in an aqueous external phase.
• Water-in-oil (w/o) emulsions have an aqueous internal phase dispersed in an oily external phase.
• O/w emulsions can be diluted with water, while w/o emulsions can be diluted with oil.
• Multiple emulsions have multiple layers of 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 are mixed with specific surfactants.
• The type of microemulsion depends on the oil and surfactant properties.
• Microemulsions have droplet diameters from 100 to 1,000 Å, significantly smaller than macroemulsions.
• Macroemulsions have larger droplets, around 5,000 Å in diameter.
• Microemulsions can be o/w or w/o.
• Microemulsions allow more rapid and efficient absorption compared to solid dosage forms, improving oral and transdermal drug delivery.
• Macroemulsions are white and opaque, while microemulsions are cloudy, translucent, or transparent.
• Macroemulsions are thermodynamically unstable and require energy input to form, while microemulsions are thermodynamically stable and form spontaneously.

Determination Tests of Emulsion Type

• Miscibility test: o/w emulsions are stable upon water dilution but not with oil, and vice versa for w/o emulsions.
• Staining test: Oil-soluble stains indicate o/w emulsions when globules are stained, and w/o emulsions when the background is stained.
• Conductivity test: Aqueous continuous phases conduct electricity, while oily external phases do not.

Emulsion Classification

• Emulsions can be liquid or semisolid.
• Liquid emulsions can be administered orally (o/w, e.g., castor oil), topically (e.g., lotions), or parenterally (I.V. o/w, I.M./S.C. w/o).
• Semisolid emulsions are for topical use, like 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

• Emulsions allow stable mixtures of immiscible liquids for drug administration.
• Oral o/w emulsions can improve palatability via taste masking and act as carriers for lipophilic drugs.
• Sterile I.V. o/w emulsions administer nutritive oils and oil-soluble vitamins.
• I.M. and S.C. w/o emulsions prolong drug effects by slowing diffusion to tissue fluids.
• Topical emulsions can be o/w (easily removed) or w/o (softening, water-resistant).
• Smaller droplet size in emulsions enhances percutaneous absorption.

Acceptable Emulsion Characteristics

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

Disadvantages of Emulsions

• Thermodynamically unstable, requiring careful formulation.
• Require thorough shaking before dosing, reducing accuracy.
• Storage conditions can cause creaming or cracking.
• Risk of microbial contamination leading to cracking.
• More bulky than solid dosage forms.

Gibbs Free Energy in an Emulsion

• ΔG = ΔA γ, where A is the surface area of dispersed particles and γ is the interfacial tension.
• Stable emulsions need large A and small G, achieved by reducing γ.

Theories of Emulsification

Surface Tension Theory

• Liquids minimize surface area by forming spherical shapes, measured by surface tension.
• Emulsifying agents (surfactants) reduce interfacial tension and the liquids' attraction to their own molecules.
• Surfactants break up large globules into smaller ones with less tendency to reunite.

Oriented-Wedge Theory

• Emulsifying agents form monomolecular layers around internal phase droplets.
• Agents orient based on their solubility in each liquid phase.
• Hydrophilic portions orient towards water, hydrophobic towards oil.
• Agents with more hydrophilic character promote o/w emulsions, hydrophobic agents promote w/o emulsions.
• The phase where the emulsifier is more soluble becomes the continuous phase.

Plastic or Interfacial Film Theory

• Emulsifying agents form a thin film at the interface between immiscible liquids.
• This film acts as a barrier, preventing contact and coalescence of the dispersed phase.
• Emulsion stability depends on the film's toughness and flexibility.
• Solubility in the two phases determines whether o/w or w/o emulsions form.

Preparation of Emulsions: Affecting Factors

• Emulsifying agents, pH, and the ratio of internal to external phases influence emulsion stability.

Criteria for Selecting Emulsifying Agents

• Compatibility with other ingredients.
• Stability during preparation and storage.
• Nontoxic and safe for consumption, with minimal odor, taste, or color.
• Promotion of effective emulsification.

Common Types of Emulsifying Agents

Carbohydrate Materials

• Acacia, tragacanth, agar, chondrus, and pectin form hydrophilic colloids and o/w emulsions.
• Acacia is used in extemporaneous emulsions.
• Tragacanth and agar thicken acacia-emulsified products.
• Microcrystalline cellulose regulates viscosity in commercial emulsions.

Protein Substances

• Gelatin, egg white, and casein produce o/w emulsions.
• Gelatin-based emulsions can become more fluid over time.

High Molecular Weight Alcohols

• Stearyl alcohol, cetyl alcohol, and glyceryl monostearate are thickening agents and stabilizers for o/w emulsions in external applications.
• Cholesterol and cholesterol derivatives promote w/o emulsions.

Surfactants

• Amphiphilic molecules with hydrophilic heads and lipophilic tails.
• Can be anionic, cationic, or nonionic.
• Anionic and cationic agents neutralize each other.
• Nonionic emulsifiers do not ionize.

Finely Divided Solids

• Colloidal clays like bentonite, magnesium hydroxide, and aluminum hydroxide form o/w emulsions when added to a greater volume of aqueous phase.
• If added to oil with a greater volume, bentonite can form w/o emulsions.

Mechanisms of Action of Emulsifying Agents

• Monomolecular: Form coherent flexible films (e.g., potassium laurate, Tween).
• Multimolecular: Form strong rigid films (e.g., acacia, gelatin) for O/W emulsions.
• Solid particles: Ionized solids form films (e.g., bentonite, magnesium hydroxide) creating an electrical barrier.

Auxiliary Emulsifying Agents

• Lipophilic: High molecular weight alcohols like stearyl and cetyl alcohol thicken and stabilize o/w emulsions.
• Hydrophilic: Tragacanth and agar thicken acacia-emulsified products.

Hydrophilic-Lipophilic Balance (HLB) System

• Emulsifying agents are categorized by their HLB value, indicating polarity.
• Values range from 1 to 20 (sometimes up to 40).
• Higher numbers indicate greater polarity (hydrophilic), lower numbers indicate greater lipophilicity.
• HLB 3-6: Lipophilic, favoring w/o emulsions.
• HLB 8-18: Favoring o/w emulsions.

HLB Activity Assignments

• Antifoaming: 1-3
• Emulsifiers (w/o): 3-6
• Wetting agents: 7-9
• Emulsifiers (o/w): 8-18
• Solubilizers: 15-20
• Detergents: 13-16
• Selecting agents with similar HLB to the emulsion is crucial for stability.

Required HLB

• Oils, waxes, and other emulsion components have an individual "Required HLB."
• Mineral oil: HLB 4 for w/o emulsions, 10.5 for o/w emulsions.

Blending Emulsifying Agents and Calculations

• Stability is achieved by selecting emulsifying agents with HLB values similar to the intended emulsion.
• Combining two or more emulsifiers may be necessary to achieve the required HLB value.
• HLB values are additive.
• Total HLB = fraction A (HLBA) + fraction B (HLBB).

Preparation Methods

Small-Scale Emulsion Preparation Methods

• Equipment: Mortar and pestle or mechanical blenders.
• Techniques: Continental (dry gum), English (wet gum), bottle (Forbes bottle) methods.

Continental or Dry Gum Method

• Triturate emulsifying agent (e.g., acacia) with oil, then add water (4:2:1 ratio).
• Use a dry, rough mortar for proper grinding.

English or Wet Gum Method

• Create a mucilage of the emulsifying agent with water, then slowly incorporate oil.

Bottle or Forbes Bottle Method

• Suitable for volatile oils; shake powdered acacia with oil, then add water in portions.

Important Considerations on Emulsion Preparation

• Dissolve water-soluble ingredients in the aqueous phase and oil-soluble components in the oil.
• Add solid substances (preservatives, stabilizers, colorants) as solutions.
• Warm phases if using solid or semisolid fats, waxes, or surfactants.
• Add substances that interfere with stability last.
• Avoid adding alcohol directly to the primary emulsion.
• Transfer the emulsion to a graduate and adjust to volume.
• Forbes bottle method isn't suited for viscous oils.
• Use the dry gum method for mixtures of fixed and volatile oils.

Auxiliary Methods

• Hand homogenizers can improve quality by reducing globule size.

In Situ Soap Method (Nascent soap method)

• Develops calcium and soft soaps. Calcium soaps are w/o emulsions made by mixing vegetable oils (e.g., oleic acid) with limewater.

Large-Scale Preparation

• Mixing tanks with high-speed impellers.
• Colloid mills or large homogenizers refine the emulsion.
• Industrial homogenizers can handle up to 100,000 L per hour.

Stability of Emulsions

• Instability includes flocculation, creaming/sedimentation, coalescence/aggregation, cracking/breaking, and phase separation.

Flocculation

• Droplets aggregate without changing primary droplet size, forming clumps.

Creaming

• Globules rise to the top or settle to the bottom. Reversible with gentle agitation.

Stokes Equation

• Rate of separation depends on particle size, density difference, and external phase viscosity.
• Larger particle size, greater density difference, and lower viscosity increase the rate of creaming.

Strategies for Enhanced Stability

• Reduce particle size.
• Minimize density difference.
• Increase external phase viscosity.

Coalescence and Breaking (Cracking)

• Droplets merge to form larger droplets, leading to phase separation (breaking). Irreversible.

Phase Inversion

• Exchange between the disperse phase and the medium. For example, an o/w emulsion may with time or change of conditions invert to a w/o emulsion which occurs when the dispersed phase exceed a theoretical maximum of 74% of the total volume.

Consideration for Temperature, Light, Environmental Factors, and Storage

• Avoid extremes of cold and heat.
• Protect against light, air, and microorganisms.
• Use light-resistant containers and antioxidants.
• Ensure containers are tightly closed.

Preservation of Emulsion

• Use fungistatic preservatives like methylparaben and propylparaben for o/w emulsions.
• Add 12-15% alcohol to oral o/w emulsions.

Therapeutic Examples of Oral and Topical Emulsions

Oral Emulsions

Mineral Oil Emulsion

• O/w emulsion with mineral oil, acacia, syrup, vanillin, alcohol, and water made by the dry gum method (4:2:1).
• Used as a lubricating cathartic.

Castor Oil Emulsion

• Laxative for constipation and colon preparation.

Simethicone Emulsion

• Defoaming agent for gastrointestinal gas relief.

Topical Emulsions

Lotions

• Many hand and body lotions are o/w emulsions.

Shampoos

• Cleansing solution, emulsion, or suspension dosage forms.

Liniments

• Alcoholic or oleaginous solutions or emulsions for external use, labeled accordingly, usually prepared in the same manner as solutions, emulsions, or suspensions