Preserving Pharmaceutical Emulsions

Emulsions are unique biphasic liquid systems where two normally immiscible liquids (like oil and water) are blended with the help of emulsifying agents (surfactants). From a thermodynamic perspective, any emulsion is an unstable system because liquids naturally tend to separate to reduce their high interfacial energy.

Emulsion stability is therefore defined as the system's ability to resist changes in its physicochemical properties over time.

📉 Mechanisms of Emulsion Breakdown

Emulsion stability is crucial in countless applications, from pharmaceuticals and personal care to food and petroleum. Instability is caused by several well-known mechanisms:

Creaming/Sedimentation: Droplets move up (creaming) or down (sedimentation) under gravity, forming concentrated layers at the top or bottom. This is reversible but undesirable.
Flocculation: Droplets aggregate loosely into clumps, but their individual interfaces remain intact. This increases the rate of creaming.
Coalescence: The thin film separating the droplets breaks, causing small droplets to merge into larger ones. This is irreversible and leads to complete phase separation (breaking or cracking).

Interestingly, while stability is usually desired, it is undesirable in processes like oil recovery or wastewater treatment, where oil-water separation is the goal.

🔬 Interfacial Rheology: Predicting Stability

Interfacial rheology is a specialized branch of rheology that studies the flow and deformation properties of unique two-dimensional systems formed at interfaces (like the oil-water boundary).

Measurements of interfacial rheology are key to predicting emulsion stability.

Elasticity and Viscosity: The layer formed by adsorbed proteins or surfactants at the interface has both elastic (solid-like) and viscous (liquid-like) properties. The elasticity of this adsorbed film is directly related to emulsion stability; a more elastic film resists coalescence better.
Measurement: Techniques like the pulsating drop method or floating needle rheometry (for interfacial shear rheology) are used to study the properties of this stabilizing layer.

Example: Non-Ionic Surfactants

Studies on non-ionic polyoxyethylene surfactants (like $\text{C}_{10}\text{EO}_6$ and $\text{C}_{10}\text{EO}_{14}$ ) show that increasing the number of ethylene oxide ( $\text{EO}$ groups enhances the dilatational elasticity of the film. Therefore, the larger $\text{C}_{10}\text{EO}_{14}$ surfactant is likely to form more stable layers against coalescence than the shorter $\text{C}_{10}\text{EO}_6$ .

Asphaltenes in Crude Oil

In oil recovery, complex emulsions are formed stabilized by asphaltenes (complex organic molecules) that adsorb at the oil-water interface. This stable emulsion is unwanted as it increases transport costs and pipe corrosion. Interfacial tension and rheology measurements are used to determine the stability level caused by these asphaltenes.

🦠 Preservation of Emulsions: The Microbial Threat

Emulsions are highly susceptible to microbial contamination because many of their ingredients serve as nutrients:

Nutrients: Non-ionic and ionic surfactants, glycerin, and natural polysaccharide emulsifying agents can all promote bacterial growth.
Oil Phase: Even oils like arachis oil can promote the growth of fungi (e.g., Aspergillus or Rhizopus).

Consequences of Microbial Growth

The growth of micro-organisms causes undesirable changes, leading to:

Phase separation (instability).
Discoloration.
Gas/odor formation.
Changes in rheological properties (viscosity changes).

For these reasons, emulsions must be formulated with a preservative.

Challenges in Preservative Selection

The major challenge in preserving an emulsion is achieving an adequate concentration in the aqueous phase due to partitioning.

Partitioning: Since emulsions are heterogeneous, the preservative tends to partition between the oil and aqueous phases. However, bacteria grow only in the aqueous phase, so the concentration there is critical.
Activity: The preservative must be in its unionized form to penetrate the bacterial membrane effectively.
Binding: The preservative must remain free and not be bound to other components (e.g., weak acid preservatives lose activity as $\text{pH}$ rises, or phenols can hydrogen-bond with $\text{EO}$ groups of non-ionic surfactants like polysorbate 20).

Ideal Preservative Characteristics

An ideal preservative should be:

Non-toxic and non-irritating.
Rapid in action and broad-spectrum.
Preferably bactericidal (killing) rather than bacteriostatic (inhibiting).
Not readily attacked by micro-organisms (e.g., Pseudomonas aeruginosa can attack phenols).

Note: Emulsions for parenteral (injectable) use must be absolutely sterile. While oral and topical emulsions may not require initial sterility, they must be formulated to resist microbial attack throughout their shelf life.