Emulsion Instability and Flocculation

Emulsion Instability

• Emulsion is a thermodynamically unstable system due to positive surface free energy, which is the product of interfacial tension and surface area of the dispersed phase.
• Surface free energy is calculated by the formula: Surface Free Energy = γ × A, where A is the total surface area of the droplets and γ is the surface tension.

Flocculation

• Flocculation is the association of particles within an emulsion to form large aggregates, which can be redispersed upon shaking.
• It is a precursor to the irreversible process of coalescence and differs from coalescence in that the interfacial film and individual droplets remain intact.
• The reversibility of flocculation depends on the strength of the interaction between the droplets and the phase volume ratio.

Creaming

• Creaming occurs when the dispersed droplets or floccules separate from the disperse medium under the influence of gravitational force.
• The rate of creaming is described by Stoke's law and depends on the relative values of the densities of the two phases.
• Larger droplets cream more rapidly than smaller droplets.
• The rate of creaming can be minimized by:
  • Reducing the droplet sizes (homogenization).
  • Thickening the continuous phase using viscosity-enhancing agents.
  • Higher amounts of solid fats in the oily phase.

Coalescence

• Coalescence is the fusion of two or more droplets of the disperse phase forming one droplet.
• It occurs when the mechanical or electrical barrier is insufficient to prevent the formation of progressively larger droplets, leading to breaking (complete phase separation).
• Coalescence can be avoided by the formation of a continuous strong film that would prevent coalescence upon flocculation.

Phase Inversion

• Phase inversion is an irreversible process in which an emulsion changes from one type to another (e.g., O/W to W/O).
• The most stable range of disperse phase concentration is 30-60%.
• If the amount of disperse phase approaches a theoretical maximum of 74% of the total volume, then phase inversion may occur.

Emulsification Equipment

• The formulator determines the physical and chemical characteristics of the drug, which are essential for the selection of the appropriate type of emulsion.
• Colloid mills are used to break down large droplets into submicron droplets by forcing the emulsion through a narrow gap between a high-speed rotor and a stator.
• The mechanism of breakage in colloid mills depends on the size of the gap, the speed of the rotor, and the finish of the surfaces of the rotor and stator.

Homogenizers

• In a homogenizer, the dispersion of two liquids is achieved by forcing their mixture through a small inlet orifice at high pressure.
• A homogenizer consists of a pump that raises the pressure of the dispersion to a range of 500-5,000 psi and an orifice through which the fluid impinges upon the homogenizing valve.
• The fluid passes through a minute gap in the homogenizing valve, creating conditions of high turbulence and shear, combined with compression, acceleration, pressure drop, and impact, causing the disintegration of particles and dispersion throughout the product.