Pharmaceutical Emulsions: Types, Preparation, and Stability

Posted on May 2, 2024 in Chemistry

Pharmaceutical Emulsions

Emulsions are dispersion systems consisting of at least two immiscible fluids, or semi-solid easy-melting substances, one of which is dispersed throughout the other in the form of fine droplets. The diameter of these droplets is usually bigger than 0.5 µm. Pharmaceutical emulsions usually consist of water and oil.

Types of Emulsions

Two main basic types of emulsion can exist: oil-in-water (o/w) and water-in-oil (w/o), depending upon whether the continuous (outer) phase is aqueous or oily. The properties of emulsion depend on the character of the outer phase. A third component, the emulsifying agent, is necessary to stabilize the emulsion. It is an emulsifier, which determines the type of emulsion, though the proportion of phases is also important.

Emulsifiers Used in Pharmaceutical Emulsions

  • Insoluble (finely divided solids): silica, colloidal anhydrous; bentonite; aluminum and magnesium hydroxides
  • Natural substances and their derivatives: acacia gum, tragacanth, sodium alginate; cellulose derivatives (methylcellulose, carmellose sodium)
  • Sterol-containing substances: wool fat, wool alcohols
  • Lecithins, phosphatidylcholines: surfactants with amphoteric character
  • Synthetic and semisynthetic substances:
    • Anionic surfactants: sodium cetostearyl sulfate, sodium lauryl sulfate, sodium stearate, sodium soap, aluminum, calcium, magnesium stearate, ammonium and amine soaps
    • Cationic surfactants: cetrimide (cetyl trimethylammonium bromide)
    • Non-ionic surfactants: partial esters of glycerol (e.g., glycerol mono- and distearate), sorbitan esters (e.g., sorbitan stearate, oleate), polysorbates (e.g., Polysorbate 80), fatty alcohols (e.g., cetyl alcohol), fatty alcohol polyglycol ethers (e.g., macrogol cetostearyl ether), fatty acids polyglycol esters (e.g., macrogol stearate), poloxamers (polyoxyethylene/polyoxypropylene copolymers)
    • Amphoteric surfactants: betaines, sulfobetaines

Emulsion Stability

Particle size of emulsions, which is an important stability-affecting parameter, can be influenced by:

  • Used emulsifier, mainly by its ability to decrease the interfacial adsorption layer, which it creates at the interphase
  • Method of preparation, mainly by the amount of used mechanical work
  • Sequence of production operations

Emulsions can display several types of physical instability:

  • Creaming: dispersed phase rises to the top
  • Sedimentation: dispersed phase sinks to the bottom (w/o emulsion type)
  • Breaking: coalescence of particles of dispersed phase, separation of phases
  • Phase inversion: the change of emulsion type o/w to w/o and vice versa

According to the European Pharmacopoeia, with the exception of emulsions intended for parenteral application, they may show evidence of phase separation but should be readily redispersed on shaking. The outer phase of emulsions might succumb to chemical changes (w/o emulsions) or microbiological contamination (o/w emulsions). Chemical stability is usually ensured by antioxidants, microbiological quality is secured by preservatives.

Preparation of Emulsions

Emulsions are defined as mixtures of mutually insoluble liquids. However, they may contain semi-solid components (waxes, fats), so the preparation of emulsions often has to be performed at a higher temperature to ensure all components are in a liquid form. In such a case, both phases are usually heated separately before mixing. The temperature of the water phase should always be 5-10°C higher than the temperature of the oil phase.

There are several possible methods of emulsion preparation:

  • English method: The emulsifier (acacia gum, tragacanth, or methylcellulose) is dissolved in the phase where it is better soluble (water). The second phase is added to this solution or dispersion and homogenized in a mortar.
  • Continental method: The emulsifier is homogenized with the phase where it is worse soluble and creates a suspension. The second phase is added by parts during continuous stirring and homogenization to this suspension.
  • Method with a complex emulsifier: Usually performed by an English method. Emulsifier o/w is dissolved in a water phase, emulsifier w/o is dissolved in an oil phase. If any phase contains semi-solid components with a higher melting temperature, both phases are separately heated to the temperature approx. 60°C and then the outer phase is added to the inner phase during continuous stirring.
  • Method with an emulsifier created “in situ”: Emulsions are prepared by shaking an appropriate vial or bottle. The emulsifier arises after mixing of both phases by a chemical reaction between components of the emulsion.

Determination of Emulsion Type

Several methods can be used to determine the type of emulsion:

  1. Dilution with water and oil: A drop of emulsion is placed on the surface of water or oil and observed for dissolution or dispersion.
  2. Solubility of dyes in an emulsion: Dyes soluble in oil (e.g., Sudan II) or water (e.g., methylene blue) are mixed with the emulsion and observed for coloring.
  3. Capillary method: A drop of emulsion is placed on filter paper and observed for spreading.
  4. Electrical conductivity test: The emulsion is tested for its ability to conduct electricity.