Emulsions: Types, Macroemulsions and Microemulsions

• Emulsions are thermodynamically unstable systems of two immiscible liquids, where one liquid is dispersed as droplets in the other.
• The dispersed phase is the internal phase, while the dispersion medium is the external or continuous phase.
• A third phase, the emulsifying agent, is necessary to prepare a stable emulsion.

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 dispersed and continuous phases like oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) structures.

Macroemulsions vs. Microemulsions

• Microemulsions form spontaneously with agitation of oil and water phases using specific surfactants, whereas the type is dependent on the oil and surfactants used
• Microemulsions have much smaller droplets ranging from 100 to 1,000 Å, compared to macroemulsions.
• Macroemulsions features larger droplets, around 5,000 Å in diameter.
• Both o/w and w/o microemulsions can be formed depending on the oil and surfactant properties.
• Microemulsions can be used for oral drug delivery due to rapid absorption and better transdermal drug delivery.

Determination tests of the emulsion type

• Miscibility Test: o/w emulsions remain stable upon dilution with water and vice versa for w/o emulsions.
• Staining Test: Staining globules with colorless medium indicates o/w emulsion; staining background with colorless globules indicates w/o emulsion.
• Conductivity Test: Emulsions with water as a continuous phase conduct electricity, while those with oil do not.

Classification of emulsions by physical state:

• Liquid emulsions
• Semisolid emulsions
• Liquid emulsions are administered orally as o/w emulsions, topically as lotions, parenterally as I.V. (o/w), or I.M. and S.C. (w/o)
• Semisolid emulsions are administered topically, examples being lotions, creams, and liniments.
• The choice between o/w and w/o emulsions depends on the therapeutic agents, the desired effects, and the administration route.

Purpose and Benefits of Emulsions

• Emulsions allow pharmacists to create stable mixtures of immiscible liquids, which betters drug administration
• Orally administered emulsions are in o/w form, to improve palatability by taste masking plus act as carriers for lipophilic drugs, enhancing oral bioavailability.
• Sterile I.V. o/w emulsions are used for nutritive oil and oil-soluble vitamin administration. IV emulsions must be o/w.
• Intramuscular and subcutaneous injections as w/o emulsions drug effects are prolonged because the drug must diffuse
• Topical emulsions can be o/w or w/o, depending on therapeutic agents, desired effects, and skin conditions.

Qualities of acceptable emulsion

• Globules need to be equally dispersed throughout continuous phase
• Be physically stable, pleasing appearance and texture
• For oral have appropriate flavor
• For external use easy to spread
• Lack microorganisms and are physically stable, showing no signs of flocculation, creaming, sedimentation, and coalescence

Disadvantages of emulsions

• Pharmaceutical emulsions are thermodynamically unstable, so require careful formulation to prevent phase separation.
• Doses need to be measured carefully and need to be shaken but are always less effective than solutions
• Emulsions may be contaminated and need preservatives
• Emulsions are commonly bulky

Gibbs free energy in an emulsion

• In the equation AG = ΔΑ γ: where A is the total surface area of dispersed particles and γ is the interfacial tension
• Stable emulsions have a large "A" and a small “G” concurrently for consistent and uniform dosing, done by decreasing “y".

Theories of Emulsification, Surface Tension Theory

• Liquids minimize surface area by forming spherical shapes, which is the shape with the least surface area.
• Surface tension is a force resisting the formation of smaller droplets when two immiscible liquids come into contact.
• Emulsifying agents reduce interfacial tension which lowers each liquids reduction to their own molecules.
• Emulsifiers lower the interfacial tension between immiscible liquids so that surface-active agents break up large globules into smaller ones, which then have a lesser tendency to reunite or coalesce

Theories of Emulsification, Oriented-Wedge Theory

• Emulsifying agents form monomolecular layers around internal phase droplets which orients themselves according to their solubility in different liquids.
• In a system containing two immiscible liquids, the emulsifying agent is preferentially soluble in one of the phases and is embedded more deeply in that phase than the other.
• Molecules orient based hydrophilic (water-loving) and hydrophobic (water-hating) properties.
• Emulsifying agents with greater hydrophilic character promote o/w emulsions, while hydrophobic ones can be used as w/o emulsion
• The phase in which the emulsifier is more soluble becomes the continuous phase of the emulsion.

Theories of Emulsification, Plastic or Interfacial FilmTheory

• Emulsifying agents are at the interface between liquids, forming a thin film adsorbed on the surface of internal phase droplets.
• Film acts as a barrier, preventing dispersed phase contact and coalescence.
• Film toughness and flexibility determine stability.
• Degree of emulsifying agent solubility determines o/w or w/o emulsion.

Preparation of Emulsions

• Emulsifying agents, pH and the ratio of internal to external phases can affect emulsion formation

Criteria for Selecting Emulsifying Agents

• Compatibility is a key factor
• Emulsifying agents should be stable and safe for consumption by the patient, and they should possess minimal odor, taste, or color.
• Emulsifying agents should promote emulsification, ensuring the two immiscible phases are dispersed effectively.

Common Types of Emulsifying Agents

• Carbide Materials: Acacia, tragacanth, agar, chondrus, and pectin are naturally occurring carbohydrate agents used to form o/w emulsions. Acacia is used in extemporaneous emulsions
• Protein Substances : Gelatin, egg white, and casein are examples of protein-based emulsifiers can produce o/w emulsions.
• High Molecular Weight Alcohols: Stearyl alcohol, cetyl alcohol, and glyceryl monostearate are typically used as stabilizers for o/w emulsions and Cholesterols for w/o emulsions'
• Surfactants are amphiphilic molecules with hydrophilic heads and lipophilic tails, they are commonly anionic, cationic, or nonionic.

Auxiliary emulsifying agents

• Lipophilic: High molecular Weight Alcohols: Substances like stearyl alcohol, cetyl alcohol, and glyceryl monostearate are typically used as stabilizers for o/w emulsions.
• Hydrophilic: Tragacanth and agar are commonly used as thickening agents in acacia – emulsified products.

Hydrophilic-Lipophilic Balance (HLB) System

• Each emulsifying agent can be categorized based on their chemical makeup
• Each agent is assigned an HLB value or number indicating polarity (the numbers have been assigned up to about 40).
• High HLB values (8-18) correspond to emulsifying agents favoring oil-in-water (o/w) emulsions.
• Materials with HLB values of 3 to 6 are highly lipophilic and favor water-in-oil (w/o) emulsions.

Blending Emulsifying Agents and Calculations in the HLB System

• Stability is achieved by selecting emulsifying agents with HLB values similar to the intended emulsion
• HLB values are additive, allowing the blending of surfactants to achieve the desired total HLB value.
• Calculation example of Total HLB: Total HLB= HLBA (X) + HLBB (1-X)

Small-Scale Emulsion Preparation Methods

• Small-scale emulsions can be prepared using equipment like Wedgwood or porcelain mortar and pestle and mechanical blenders
• Laboratory Techniques use the Continental or dry gum method, the English or wet gum method and the bottle or Forbes bottle method

The continental or dry gum method

• Continental or dry gum method involves the addition of external phase to the internal phase, triturating the emulsifying agent (e.g., acacia) with oil before adding water
• 4:2:1 method
• For every four parts by volume of oil, two parts of water and one part of gum are added in preparing the initial or primary emulsion

English or Wet Gum Method

• the addition of internal phase to the external phase
• Gum mucilage is prepared before oil incorporation
• Same proportions as dry gum but different mixing order

Bottle or Forbes bottle method:

• For volatile oils and low viscosity oleaginous substances
• Mixture involves shaking

Important considerations on emulsion preparation

• Water-soluble ingredients are dissolved in the aqueous phase, and oil-soluble components in the oil phase.
• Solid substances are dissolved in water for emulsion
• Waxes can be added but temperatures need to be watched
• Bottle methods not suited for solid oils
• Dry gum used for complex solutions

Auxiliary Methods:

• An emulsion prepared can generally be increased in quality by passing it through a hand homogenizer

In Situ Soap Method (Nascent soap method):

• Calcium soaps and soft soaps are the 2 types of soaps.
• Calcium soaps are w/o emulsions that contain certain vegetable oils in combination with limewater
• Emulsifying agent is the calcium salt of the free fatty acid formed from the combination of the two entities.

Stability of Emulsions

• Instability of emulsions include flocculation and creaming or sedimentation, Coalescence or aggregation and Cracking or breaking, Phase separation
• Flocculation is aggregation of droplets together to form large units and clumps which rise or settle.
• Creaming is the process where aggregates of globules of the internal phase rise to the top or fall to the bottom of the emulsion, reversible by gentle shaking.
• The globule/particle size should be reduced, The density difference between the internal and external phases should be minimal and the viscosity of the external phase should be reasonably high: Strategies for enhanced stability

Coalescence and Breaking (Cracking)

• Droplets contact and coalesce will occur to produce a single droplet of greater the new droplet will be less than the surface areas of the two individual droplets.
• Called breaking/cracking because protective sheath is irreversible , because the protective sheath about globules of the internal phase no longer exists.

Phase Inversion

• Phase Inversion, the process of an exchange between the disperse phase
• o/w emulsion with may with time or change of conditions invert to a w/o emulsion when the dispersed phase exceed a theoretical maximum of 74% of the volume

Consideration for temperature, light, environmental factors and storage

• Protect emulsion against extremes of cold and heat
• The presence of light, air, and contaminating microorganisms can adversely affect the stability of an emulsion , Light-resistant containers should be used.
• Also use antioxidants

Preservation of emulsion

• Preservatives such as methylparaben and propylparaben are generally included in the aqueous phase of an o/w emulsion.
• Alcohol in the amount of 12% to 15% is frequently added to oral o/w emulsions for preservation.

Therapeutic examples of Oral and Topical Emulsions

• Mineral Oil Emulsion: an o/w emulsion prepared from mineral oil, acacia, syrup, vanillin, alcohol, and purified water.
• Castor Oil Emulsion: Lactative
• Simethicone Emulsion: Defoaming agent
• Topicals examples are Lotions and Shampoos
• Liniments are alcoholic or oleaginous solutions or emulsions to be rubbed on the skin.